Search PubMed⌕ Search

Biomedical subjects

J E Morley

Publications and source records attributed to J E Morley.

At least 55 records · Page 3Linked to original sources
PubMed2001

Molecular cloning, expression, and regulation of hippocampal amyloid precursor protein of senescence accelerated mouse (SAMP8).

Alzheimer's disease (AD) is associated with increased expression of amyloid precursor protein (APP) with a consequent deposition of amyloid beta peptide (Abeta) which forms characteristic senile plaques. We have noticed that the senescence accelerated mouse (SAMP8), a strain of mouse that exhibits age-dependent defects such as loss of memory and retention at an early age of 8-12 months, also produces increased amounts of APP and Abeta similar to those observed in Alzheimer's disease (AD). In order to investigate if this is due to mutations in APP similar to those observed in AD, and to develop molecular probes that regulate its expression, APP cDNA was cloned from the hippocampus of 8-month-old SAMP8 mouse. The nucleotide sequence is 99.7% homologous with that of mouse and rat, 88.7% with monkey, and 89.2% with human homologues. At the amino acid level, the homology was 99.2% and 97.6% with rodent and primate sequences, respectively. A single amino acid substitution of Alanine instead of Valine at position 300 was unique to SAMP8 mouse APP. However, no mutations similar to those reported in human familial AD were observed. When the cDNA was expressed in HeLa cells, glycosylated mature APP could be detected by immunoblotting technique. The expression could be regulated in a time- and concentration-dependent manner by using an antisense oligonucleotide specific to APP mRNA. Such regulation of APP expression may have a therapeutic application in vivo.

Aging↗
PubMed2001

Delivery across the blood-brain barrier of antisense directed against amyloid beta: reversal of learning and memory deficits in mice overexpressing amyloid precursor protein.

Amyloid beta protein (Abeta) may play a causal role in Alzheimer's disease. Previous work has shown that the learning and memory deficits that develop with aging in SAMP8 mice, a strain that overproduces Abeta, can be reversed with i.c.v. injections of an Abeta antisense phosphorothiolate oligonucleotide (Olg). Here, we showed that Olg radioactively labeled with (32)P (P-Olg) was transported intact across the blood-brain barrier (BBB) of mice by a saturable system, termed oligonucleotide transport system-1 (OTS-1). Multiple-time regression analysis found a blood-to-brain unidirectional influx rate for P-Olg of 1.4 +/- 0.39 microl/g-min and capillary depletion showed that P-Olg completely crossed the BBB to enter the parenchymal space of the brain. P-Olg was also shown to enter the cerebrospinal fluid. Transport was especially high into the hippocampus, with the percentage of the i.v. dose taken up by each gram of brain (0.865 +/- 0.115%) being about 1/100 of the i.c.v. dose. An i.v. dose of Olg 100 times that of the effective i.c.v. dose reversed the learning and memory deficits of aged SAMP8 mice. These studies show for the first time that phosphorothiolate oligonucleotides can be delivered to the brain in effective doses by intravenous administration.

Alzheimer Disease↗
PubMed2001

Examining the effect of intervention to nutritional problems of the elderly living in an inner city area: a pilot project.

OBJECTIVE: To examine the effect of interventions provided to home-delivered meal service recipients living in an inner city neighborhood for the purpose of improving their nutritional conditions. DESIGN: Intervention study. SETTING AND PARTICIPANTS: Both the Study Group (42 seniors) and the Control Group (39 seniors), all of whom are over 60 years old, received home delivered meal services. In addition, only the Study Group received the following services through the trained neighborhood residents: 1) health education, 2) referrals to other community resources for unmet health needs, and 3) follow-up services to assure that the health problems were addressed appropriately. The nutritional condition, depression and cognitive status of the Study Group were assessed by medical staff before and after the six-month intervention. The same assessments were conducted to the Control Group with the same interval. Data was analyzed using ANOVA (repeated). MEASUREMENTS: MNA, GDS, and MMSE. RESULTS: Compared to the Control Group, the nutritional condition (p=0.052) and depression (p=0.02) of the Study Group were improved, while no significant difference was observed in their cognitive status. CONCLUSION: A combination of interventions by medical professionals and by trained neighborhood residents seemed to be an effective strategy to approach nutritional problems of seniors living in inner city areas.

Aged↗
PubMed2001

Testosterone replacement in older men and women.

This article examines in detail the present state of the art concerning androgen deficiency in aging males. There is increasing evidence that testosterone replacement in hypogonadal older males can result in an improvement in quality of life. The major effects of testosterone are on libido, muscles, bone, and cognition. Less information is available concerning the role of testosterone in postmenopausal women, but testosterone replacement may have a role to play in treating disorders of libido and the sarcopenia that occurs at menopause.

Aged↗
PubMed2001

Intravenous human interleukin-1alpha impairs memory processing in mice: dependence on blood-brain barrier transport into posterior division of the septum.

Peripherally administered cytokines profoundly affect the central nervous system (CNS). One mechanism by which they could affect the CNS is by crossing the blood-brain barrier (BBB) to interact directly with brain receptors. Human and murine IL-1alpha (hIL-1alpha; mIL-1alpha) are transported across the murine BBB with a high rate of transport into the posterior division of the septum (PDS), but it is unknown whether BBB transport is relevant to their actions. Here, we injected species-specific blocking antibodies into the PDS to determine whether transport across the BBB is required for blood-borne hIL-1alpha to affect memory. Retention was impaired in a dose-dependent manner when hIL-1alpha was injected either by tail vein (i.v.) or into the PDS, with the PDS route being 1000 times more potent. About 70% of the memory impairment induced by i.v. hIL-1alpha was reversed by injecting a blocking antibody (Ab) specific for hIL-1alpha into the PDS. This shows that much of the memory impairment induced by hIL-1alpha depends on its ability to cross the BBB. Ab specific for mIL-1alpha was also effective in reversing memory impairment, showing that hIL-1alpha releases mIL-1alpha from endogenous stores. Whether the mIL-1alpha was released from peripheral stores, which would require it to cross the BBB, or from brain stores is unknown. In conclusion, these results show that exogenous, blood-borne hIL-1alpha affects memory by releasing mIL-1alpha from endogenous stores and by crossing the BBB to act at sites within the PDS.

Algorithms↗
PubMed2000

Permanent and temporary inactivation of the hippocampus impairs T-maze footshock avoidance acquisition and retention.

The hippocampus is widely recognized as playing an important role in learning and memory. Lesions of the hippocampus can disrupt spatial navigational learning and memory and injection of drugs into the hippocampus can affect both spatial navigational and nonspatial tasks. In the current studies we tested the effects of bilateral of electrolytic lesions and reversible inactivation of the hippocampus on acquisition and retention of T-maze footshock avoidance conditioning. Electrolytic lesions, which destroyed 31+/-0.04% of the hippocampus, significantly impaired acquisition and retention for T-maze footshock avoidance. No differences were found in motivation to avoid shock, open field activity, or foot shock sensitivity between lesion and control groups. Temporary inactivation of the hippocampus with lidocaine administered immediately before training disrupted acquisition and retention for T-maze footshock avoidance. Temporary hippocampal inactivation performed just prior to retention testing and post-training inactivation in mice trained to first avoidance had no effect on retention. However, temporary post-training inactivation in 'undertrained' (enough trials to remember 1 week later if treated with saline, but not allowed to make the avoidance response) mice impaired retention. The current findings indicate that the hippocampus plays an important role in learning and memory processing in the aversive T-maze paradigm.

Animals↗
PubMed2000

Identification of age-dependent changes in expression of senescence-accelerated mouse (SAMP8) hippocampal proteins by expression array analysis.

Aging is associated with extensive cognitive impairments, although the biochemical and physiological basis of these deficits are unknown. As the hippocampus plays a vital role in cognitive functions, we have selected this tissue to analyze changes in gene expression at two different ages. Array technology is utilized to explore how gene expression in hippocampus is affected by accelerated cognitive impairment in Senescence-Accelerated Mouse (SAM P8) strain. We show that the expression of genes associated with stress response and xenobiotic metabolism are strongly affected at a time when cognitive impairment occurs. Affected genes include those involved both in signaling and chaperone function. The effector and regulator family of chaperones, which play an important role in protein folding, and also the xenobiotic metabolizing enzymes that play crucial role in antioxidant systems, show significant changes in gene expression between 4 and 12 months.

Aging↗
PubMed2000

Estradiol potentiates acetylcholine and glutamate-mediated post-trial memory processing in the hippocampus.

There is increasing evidence that estrogen is involved in CNS activity, particularly memory. Several studies have suggested that estrogen improves memory by enhancing cholinergic and glutamatergic activity. In the present studies, we examined the effects of administration into the hippocampus of 17 beta-estradiol and estrone on retention of T-maze footshock avoidance in female ovariectomized mice. Both 17 beta-estradiol and estrone improved retention on an equimolar basis in a dose-dependent fashion. We then used the T-maze footshock paradigm to test whether a dose of 17 beta-estradiol ineffective as a single injection (subthreshold) could potentiate the effects of arecoline, a cholinergic agonist, or L-glutamate, a glutamatergic agonist, on retention. The dose of either arecoline or L-glutamate needed to improve retention was reduced at least ten-fold by the low dose of 17 beta-estradiol. These findings support the concept that estrogen improves memory by potentiating the activity of the cholinergic and glutamatergic systems.

Acetylcholine↗
PubMed2000

The effect of cholinergic, GABAergic, serotonergic, and glutamatergic receptor modulation on posttrial memory processing in the hippocampus.

Though the hippocampus is widely recognized as important in learning and memory, most of the evidence for this comes from animal lesion and human pathological studies. Due to the relatively small number of drugs that have been tested in the hippocampus for their ability to alter posttrial memory processing, there is a general impression that memory processing involves only a few neurotransmitters. We have evaluated the effects of cholinergic, GABAergic, serotonergic, and glutamatergic receptor agonists and antagonists for their ability to facilitate or impair retention. CD-1 mice received acute intrahippocampal drug infusion following footshock avoidance training in a T-maze. Retention was tested 1 week after training and drug administration. The results indicate that receptor agonists of acetylcholine and glutamate improved retention, while antagonists impaired retention. However, scopolamine did not impair retention, but M1 and M2 antagonists did. Receptor agonists of serotonin and GABA impaired retention, while antagonists improved retention. Drugs acting on 5-HT-1 and 5-HT-2 as well as GABA(A) and GABA(B) receptor subtypes did not differentially effect retention.

Animals↗
PubMed2000

Modulation of memory processing in the cingulate cortex of mice.

To evaluate the possible role of the cingulate cortex in memory processing for training using a noxious stimulus, we trained mice on foot shock avoidance in a T-maze. Cholinergic, GABAergic, serotonergic, and glutamatergic agonists and antagonists were administered into the cingulate cortex immediately after training. Retention for the foot shock avoidance training was tested 1 week later. The results indicate that muscarinic and nicotinic agonists improved retention, while antagonists impaired it. GABA and serotonin agonists impaired retention, while antagonists improved it. Drugs acting on GABA(A) and GABA(B) receptors had similar effects on retention, as did drugs acting on serotonin 1 and 2 receptor subtypes. Glutamate improved retention, and AP5, an antagonist of the excitatory amino acid site of the NMDA receptor, impaired retention. The cingulate cortex, like other parts of the limbic system, is involved in memory processing that occurs shortly after training.

Acetylcholine↗
PubMed2000

Peripheral administration of CRF and urocortin: effects on food intake and the HPA axis in the marsupial Sminthopsis crassicaudata.

The hypothalamic peptides corticotrophin releasing factor (CRF) and urocortin (UCN) decrease food intake and increase energy expenditure when administered either centrally or peripherally to rodents. The effects of CRF and UCN on food intake in other mammals (for example marsupials), however, are not known. Peripherally administered CRF induced cortisol release in the marsupial Sminthopsis crassicaudata via the CRF1 receptor, and central CRF administration potently decreased food intake, as in rodents. When peripherally administered, both CRF and UCN decreased food intake in S. crassicaudata, but UCN was considerably more potent ( approximately 50 fold) in this regard. The anorectic effects of CRF and UCN were not blocked by the CRF1 receptor antagonist antalarmin, suggesting that the peripheral effects of CRF and UCN on food intake are mediated primarily by the CRF2 receptor.

Adrenal Glands↗
PubMed2000

Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice.

beta amyloid protein (Abeta) is a 40-43 amino acid peptide derived from amyloid precursor protein (APP). Abeta has been implicated as a cause of Alzheimer's disease (AD). Mice with spontaneous or transgenic overexpression of APP show the histologic hallmarks of AD and have impairments in learning and memory. We tested whether antisense phosphorothiolated oligonucleotides (AO) directed at the Abeta region of the APP gene given with or without antibody directed at Abeta could reverse the elevated protein levels of APP and the behavioral impairments seen in SAMP8 mice, a strain which spontaneously overexpresses APP. We found that intracerebroventricular (ICV) administration of antibody with either of two AOs directed at the midregion of Abeta improved acquisition and retention in a footshock avoidance paradigm, whereas two AOs directed more toward the C-terminal, a random AO, and vehicle were without effect. Three injections of the more potent AO given without antibody reduced APP protein levels by 43-68% in the amygdala, septum, and hippocampus. These results show that AO directed at the Abeta region of APP can reduce APP levels in the brain and reverse deficits in learning and memory.

Age Factors↗
PubMed2000

Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory.

Senescence accelerated (SAMP8 [P8]) mice develop age-related deficits in memory and learning. We show that increased expression of amyloid precursor protein (APP) and its mRNA in the hippocampus are also age-related. Immunocytochemical data suggest that a critical amount of APP expression may be needed to generate amyloid (Abeta) protein plaques in the hippocampus. Deficits in acquisition and retention test performance were alleviated by administration of antibody to Abeta protein into the cerebral ventricles. This reversal of cognitive deficits provides a link between increased expression of both APP and Abeta protein and learning and memory loss in these mice.

Age Factors↗
PubMed2000

The Life Care Center of St. Louis experience with subacute care.

The Life Care Center of St. Louis is a 100-bed, freestanding, subacute care facility. The major differences between subacute care facilities and nursing homes are described. The problems associated with dealing with medically complex conditions in a subacute care facility are stressed. The center's approach to rehabilitation is reviewed in detail. The utility of the Functional Independence Measure in subacute care settings is discussed. Common conditions seen in subacute care facilities are briefly reviewed.

Activities of Daily Living↗
PubMed2000

Management of nutritional problems in subacute care.

Poor nutritional status is one of the major factors associated with functional decline and mortality in older persons. Older persons are at increased risk for malnutrition because of the physiologic anorexia of aging. During a stay in a subacute care facility, attention to nutrition is a major component of the rehabilitative process. The pathophysiology of malnutrition, diagnostic techniques available to diagnose malnutrition, causes and management of protein energy malnutrition, specific nutritional problems caused by vitamin and trace element deficiency, and nutritional management of specific diseases (e.g., hip fracture and diabetes mellitus) are reviewed.

Humans↗
PubMed2000

Assessment of protein energy malnutrition in older persons, part I: History, examination, body composition, and screening tools.

Protein-energy malnutrition is a prevalent problem in older persons. Its relation to increased morbidity and mortality has been well documented. Early recognition of malnutrition allows for a timely intervention. A large proportion of chronic diseases affecting older persons can be either prevented or significantly improved by improving nutrition, which underscores the importance of developing a screening system that can trigger a more comprehensive evaluation when indicated. Screening for malnutrition in older persons can be difficult because of the normal age-related changes in many of the commonly used parameters. A comprehensive nutritional evaluation includes a complete history and physical examination in addition to a more specific nutrition-oriented assessment. Specific nutritional assessment includes estimating food intake, anthropometric measurements, and evaluation of several biochemical parameters commonly affected by changes in nutritional status. In this article, we review the commonly used tools for nutritional assessment in older persons. The goal is to promote disease-free, active, and successful aging.

Adipose Tissue↗