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Biomedical subjects

R L Dean

Publications and source records attributed to R L Dean.

At least 37 records · Page 2Linked to original sources
PubMed1991

Preparing for networking information systems in health care organizations.

Because the health care administrator faces unprecedented demands concerning information, well-designed and carefully selected information systems have become a critical factor in the viability and survival of health care institutions. Local area network systems are having a significant impact in this regard. Among their advantages are flexibility, dependability, low cost, and modularity. Health care facilities, have found networking to be a simple, cost-effective solution to collecting, processing, and distributing large volumes of data. The keys to a successful implementation recommended in this article should assist health care professionals once they have made the hard decision to use a local area network to process their day-to-day transactions.

Contract Services↗
PubMed1990

Ferritin is a translationally regulated heat shock protein of avian reticulocytes.

Heat-shock avian reticulocytes exhibit enhanced synthesis of a greater than 450-kDa protein. Biochemical, immunochemical, and visual criteria were used to identify this protein as the iron storage protein ferritin. The 21-kDa ferritin subunits synthesized during heat shock are similar in size and pI to the subunits that are constitutively synthesized. The 2-6-fold heat shock-induced increase in ferritin synthesis appears to be regulated at the translational level as it is insensitive to actinomycin D. Northern and dot-blot hybridization analyses of cytoplasmic RNAs with avian H-ferritin cDNA fragments support the contention that the heat shock stimulation of ferritin synthesis is translationally regulated. These latter studies demonstrate that the heat shock-induced synthesis of ferritin does not involve a change in the amount of total cytoplasmic ferritin mRNAs, but rather appears to entail a translocation of cytoplasmic H-ferritin mRNAs from a polyribosome-free, translationally repressed state to a polyribosome-associated, translationally active state. These results suggest that thermally stressed avian reticulocytes have a critical and functional need for the synthesis of additional ferritin and that its enhanced synthesis, unlike the new and/or enhanced synthesis of the well-established avian heat shock proteins, is regulated wholly at the translational level.

Animals↗
PubMed1989

Rapid purification of ferritin from lysates of red blood cells using proteinase-K.

A simple, rapid, and novel procedure for purifying ferritin from the postnuclear supernatant of red blood cell lysates is described. This report establishes the resistance of commercially available holo- and apo-ferritins to proteinase-K digestion, and documents how the use of this enzyme, in conjunction with the well-documented resistance of ferritins to heat denaturation (75-80 degrees C for 10 min), makes it possible to obtain high yields (greater than 90%) of pure, undegraded ferritin from the postnuclear supernatant of hypotonically or Triton X-100 lysed red blood cells. The resultant purified ferritin contains the same amount of iron as ferritin not treated with proteinase-K and, as judged by one- and two-dimensional gel electrophoresis and electron microscopy, consists of intact ferritin with a subunit isoform composition identical in molecular mass and isoelectric points to that obtained from ferritin prepared in the absence of this enzyme.

Animals↗
PubMed1986

Behavioral recovery following bilateral lesions of the nucleus basalis does not occur spontaneously.

Recent studies have shown that rats given bilateral ibotenic acid lesions of the nucleus basalis (NBM) exhibit significant impairments on tasks requiring recent or trial-specific memory. However, despite the persistence of cholinergic deficiencies in the cortical projection area, the memory impairments gradually recover over a period of several months of training. Moreover, in one study, the behavioral recovery on a radial arm maze retention task was shown to generalize to a completely different behavior paradigm (passive avoidance) on which the animals had received no prior experience. The present study was performed to determine the extent to which this generalized recovery of performance on memory tasks is dependent upon extensive post-lesion training. Rats were given ibotenic acid lesions of the NBM and were then passively detained in their home cages for six months. Contrary to animals which had received post-surgical radial arm maze experience, the animals detained in their home cages displayed a significant retention impairment when tested on the passive avoidance task, suggesting that the experience the animals receive is an important factor for whether post-lesion functional recovery occurs. This study also confirms that the loss of cholinergic markers following bilateral, NBM lesions persists for at least several months, or longer.

Animals↗
PubMed1986

Heat shock induced changes in the gene expression of terminally differentiating avian red blood cells.

Reticulocytes, purified from the blood of quail and chickens recovering from anaemia, respond to heat shock by the new and (or) enhanced synthesis of heat-shock protein (HSPs) with relative molecular masses of greater than 400,000, 90,000, 70,000, and 26,000 (quail) or 24,000 (chicken) and the depressed synthesis of many proteins normally produced at a control temperature. The synthesis of these HSPs is noncoordinate since the expression of each protein depends upon the particular temperature and duration of the time at that temperature. Separation of proteins from quail reticulocytes into Triton X-100 soluble and insoluble fractions demonstrates that the 70,000 and 26,000 Da HSPs are found in both fractions, whereas the greater than 400,000 and 90,000 Da HSPs are located only in the detergent-soluble fraction. Triton X-100 fractionation also reveals that there are three isoelectric variants of the 70,000 Da HSP and that they are constitutively synthesized and selectively partitioned between cellular compartments. Heat shock induced synthesis of the 90,000, 70,000, and 26,000 Da quail HSPs is prevented by actinomycin D, while enhanced synthesis of the greater than 400,000 Da HSP is unaffected by this inhibitor. These results demonstrate that nucleated, terminally differentiating avian red blood cells are capable of responding to heat stress by rapid changes in their highly restricted "program" of gene expression.

Anemia↗
PubMed1985

Selective memory loss following nucleus basalis lesions: long term behavioral recovery despite persistent cholinergic deficiencies.

Rats were trained for several months to perform a radial arm maze task and then given either sham or ibotenic acid lesions of the nucleus basalis magnocellularis (NBM), the primary cholinergic projection to the neocortex. The lesion produced a profound and apparently selective disturbance in memory for recent events. Further testing revealed that although the memory deficit persisted for several weeks, a gradual but complete recovery eventually occurred. Moreover, when these functionally recovered rats were later tested on a passive avoidance task that is normally sensitive to lesions of the NBM, no deficit was found. Thus, the post-lesion recovery of function generalized to a different memory test, upon which no post-lesion practice had been given. Post-mortem determinations revealed that the lesions caused marked neurodegeneration of the NBM, and decreases in both cortical choline acetyltransferase activity and high affinity choline uptake, but had no effect on density of muscarinic receptors. No evidence of neuronal recovery or neurochemical compensatory changes in the cholinergic system was found in the cortical projection areas, lesion site, or in parallel cholinergic systems terminating in the hippocampus or olfactory bulb. These results support the idea that the cortically-projecting cholinergic cells of the NBM normally play an important role in mediating recent memory. However, they also demonstrate that any simple relationship between the function of this brain region and the mediation of recent memory is unlikely. Finally, the results of this study direct attention toward issues related to the mechanisms involved with the recovery of function, and the extent to which degeneration of this brain area may contribute directly to the severe disturbance of cognitive function associated with certain neurodegenerative diseases (e.g., Alzheimer's, Pick's and Parkinson's disease).

Alzheimer Disease↗
PubMed1985

Hippocampal muscarinic receptor loss following trimethyl tin administration.

The effects of trimethyl tin on passive and active avoidance behavior, hippocampal muscarinic receptors and hippocampal cell destruction were examined in male rats. The animals were intubated with 18 mumoles/kg (3.5 mg/kg) of TMT hydrochloride or vehicle. When tested two weeks later treated animals exhibited marked deficits in retention of passive avoidance and extinction of active avoidance tasks. Receptor binding analysis, using 3H-QNB, revealed a significant decrease (21%) in muscarinic receptor density in the hippocampus. Histological examination of the hippocampus revealed a concomitant loss in pyramidal cells in these animals. These results suggest that muscarinic receptors reside on the hippocampal pyramidal cells and that these cells and receptors may be involved in retention of passive avoidance behavior.

Animals↗
PubMed1985

Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: amelioration of passive avoidance deficits without changes in psychomotor task performance.

A series of studies was conducted to evaluate the effects of phosphatidylserine (PS) in aged Fischer 344 rats. No effects were observed in any of four psychomotor tasks in which aged rats normally show deficits, nor on measures of shock sensitivity. However, significant dose-related effects on retention of passive avoidance were observed when PS was given both 30 min prior to training and retention. Further, in a second experiment similar positive effects were observed when PS was given only 30 min prior to training, as well as only 5 min following training. These results suggest that one effect of PS may include an ability to enhance neural events involved in the encoding or consolidation of new information into memory.

Age Factors↗
PubMed1985

Synthesis of heat shock proteins in quail red blood cells following brief, physiologically relevant increases in whole body temperature.

Cultured RBCs from quail respond to thermal stress (heat shock) by a rapid and dramatic change in gene expression. This change in gene expression includes the new and/or enhanced non-coordinate synthesis of a small group of heat shock polypeptides (HSPs) having molecular masses of 90,000, 70,000 and 26,000. RBCs obtained from hyperthermic quail exhibit a change in gene expression similar to that observed in RBCs heat-shocked in vitro. Since in vitro studies have linked the synthesis of HSPs in heat-stressed cells with thermotolerance, the similar change in gene expression in RBCs from hyperthermic quail suggests that, here too, this cellular response may be an important homeostatic mechanism by which avian RBCs cope with and/or survive hyperthermic conditions.

Animals↗
PubMed1983

Chronic administration of cholinergic agents: effects on behavior and calmodulin.

Rats were implanted subcutaneously with Alza pumps and 0.9% saline, physostigmine, or scopolamine were continuously infused for 15 days. Twenty-four hours after removal of the pumps all animals were trained on a single trail passive avoidance task. Twenty-four hours after training they were tested for retention. Following behavioral testing, animals were sacrificed, brain regions dissected, frozen and stored (-20 degrees C) for calmodulin determinations. Animals which had previously received chronic infusions of scopolamine performed significantly better than controls, while those which previously received chronic infusions of physostigmine performed significantly worse during the retention test. No significant differences in calmodulin levels (soluble or particulate) were detected across brain regions or drug groups. These results indicate that continuous chronic infusion of drugs which can facilitate or inhibit CNS cholinergic activity can induce performance changes on a learning task opposite to those resulting following the acute administration of these same drugs.

Animals↗
PubMed1983

Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat.

The nucleus basalis magnocellularis (NBM) is the name given to a group of cholinesterase-reactive neurons in the ventromedial corner of the globus pallidus of the rat. This cell group appears to be the major extrinsic source of cortical acetylcholine and is believed to be homologous to the nucleus basalis of Meynert in primates. The excitotoxin ibotenic acid (2.4 micrograms/0.4 microliter) was infused bilaterally into the ventromedial globus pallidus. These lesions depleted frontal cortical choline acetyltransferase (CAT) by a third. Neurotoxic lesions of the dorsolateral globus pallidus did not affect cortical CAT activity. Neither lesion affected the rats' performance on a battery of psychomotor tasks or on tests of shock sensitivity. Rats with NBM lesions were mildly impaired in the acquisition of a one-way active avoidance response, but did not differ from the other groups on extinction of the task. The NBM lesioned rats exhibited a severe deficit in the retention of a passive avoidance response. This effect was visible both 24 hours and one hour after training. Experimental controls suggested that the poor performance of the NBM lesioned rats involves a deficit in learning and/or memory of the training trial. Lesions of the dorsolateral globus pallidus also produced an impairment of passive avoidance retention, but this impairment was not as severe as that following NBM lesions. These results are discussed as they relate to the behavioral role of cholinergic innervation of the cortex, and the development of animal models for disorders involving cortical cholinergic deficiencies, including senile dementia of the Alzheimer's type.

Acetylcholine↗
PubMed1983

Comparison of the effects of heat shock and metal-ion stress on gene expression in cells undergoing myogenesis.

Subjecting 9-day-old quail embryos to an elevated temperature in ovo causes limb, breast, and brain tissues to shift their patterns of protein synthesis from the production of a broad spectrum of different proteins to the new and (or) enhanced synthesis of a small number of heat-shock proteins (HSPs). The HSPs synthesized by undifferentiated breast tissue in ovo (relative masses (Mrs) 88 000, 82 000, 64 000, and 25 000) are similar to those synthesized by explanted breast tissue or by primary cultures of breast myoblasts heat-shocked in culture. Heat-shocked, 120-hour-old myotube cultures synthesize HSPs similar to those detected in heat-shocked myoblasts except that myotubes also exhibit enhanced synthesis of a 55 000 dalton polypeptide and little or no synthesis of a 25 000 dalton HSP; the failure to thermally induce a 25 000 dalton polypeptide in myotubes is related to the fused nature of these cells rather than to their state of differentiation. Myoblasts, as well as myotubes, cultured in the presence of elevated amounts of arsenite, copper, or zinc also synthesize new and (or) enhanced amounts of polypeptides with isoelectric points and immunochemical properties similar to the 25 000 and 64 000 dalton HSPs. However, elevated levels of these metal ions fail to stimulate new and (or) enhanced synthesis of other HSP-like proteins. These results demonstrate that, although the protein synthetic response of myogenic cells to chemical and thermal stress may be similar in some respects, a number of the synthetic responses are clearly different.

Animals↗
PubMed1983

The acquisition of thermal tolerance in larvae of calpodes ethlius (lepidoptera) and the in situ and in vitro synthesis of heat-shock proteins.

Larvae of Calpodes ethlius (Lepidoptera) reared at 22 degrees C die after 1 h at 45 degrees C, but they acquire the ability to tolerate 1 h at 45 degrees C if they are first exposed to 37 degrees C for 1 or 2 h. Incubation of intact larvae at 37 degrees C for 1 h induces the new and (or) enhanced synthesis of a similar family of polypeptides (relative masses (MrS) approximately 22 000) in all tissues examined (silk gland, fat body, wing discs, central nervous system, and muscle). When these same tissues are cultured at 37 degrees C for 1 h, the new and (or) enhanced synthesis of at least 5 polypeptides (MrS approximately 95 000, 81 000, 74 000, 26 000, and 22 000) is evident. The more dramatic response elicited from cultured tissues by heat shock results, presumably, from the added stress of dissection. The new and (or) enhanced synthesis of polypeptides with MrS of approximately 22 000 by tissues of intact larvae, incubated at 37 degrees C for 1 h, may be related to the acquisition of thermal tolerance by similarly treated larvae. These results suggest that the induced synthesis of these polypeptides is an integral part of a ubiquitous molecular mechanism involved in the development of thermal tolerance.

Adaptation, Physiological↗
PubMed1982

The cholinergic hypothesis of geriatric memory dysfunction.

Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.

Acetylcholine↗
PubMed1982

Neuropeptide effects on memory in aged monkeys.

The effects of several neuropeptides were evaluated using a non-human primate model of age-related memory impairments. Several doses of ACTH4-10, lysine vasopressin, arginine vasopressin, oxytocin and somatostatin were each tested in several aged monkeys. Because data from a large number of non-drug control sessions was collected before, during and after this study, it was possible to define the normal range of control performance for each monkey and statistically determine whether a change in performance under any single dose of drug reflected a significant change from the particular monkey's normal baseline performance. Although none of the neuropeptides produced consistent group effects, evaluations of individual subjects against their own baseline performance revealed reliable changes at certain doses. Arginine vasopressin appeared to produce the best overall effects with three of the five monkeys exhibiting reliable changes in performance from baseline. These same three monkeys also responded positively to the lysine form. Oxytocin impaired memory in three of the six aged monkeys tested over a wide range of doses. Three of six aged monkeys performed better under ACTH4-10 compared to baseline; however, in two of these cases only a single dose was effective. The performance of only one subject was improved under somatostatin, and this was at a single dose only. The data reported here provide evidence for neuropeptides producing behavioral improvement in non-human primates using an appetitive task, eliminating a popular criticism that the data in this literature has depended too heavily on the testing of rodents in shock-motivated tasks. Additionally, the improvements observed in this study involve a behavior that it naturally impaired by age and one which has many operational similarities and some empirical relevance to measures of recent memory in humans. However, these positive findings must be tempered by the lack of robust effects and high individual variation observed.

Adrenocorticotropic Hormone↗