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D A Matthews

Publications and source records attributed to D A Matthews.

123 records · Page 7Linked to original sources
PubMed1976

An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration.

Synapses in the rat dentate gyrus are rapidly lost after removal of the primary input from the entorhinal cortex. In this paper we describe the extent and time course of degeneration and in the subsequent paper the nature of the reinnervation processes. They synapses of entorhinal afferents are remarkably concentrated in their zone of termination. Unilateral removal of the rat entorhinal cortex results in the loss of about 86% of all synapses in the outer three-fourths of the molecular layer of the epsilateral dentate gyrus. Entorhinal synapses are all asymmetric (Gray type I) and terminate on dendritic spines. Analysis of the degeneration reaction provides a means to examine the characteristics of the loss of a relatively homogeneous afferent on a single cell type. The morphological characteristics of the the degenerating terminals showed some heterogeneity; both the electron lucent and electron dense types of degenerating terminals were identified. The electron lucent type was observed only at short survival times. The time course of the loss of degenerating terminals was resolvable into two components, each of which followed first order decay kinetics. Thus degenerating entorhinal terminals behaved as a population which disappeared randomly at a rate dependent on the fraction of terminals present at any time. The loss of degenerating terminals was accompanied by the loss of postsynaptic sites. At short survival times the majority of postsynaptic sites (defined by the presence of a postsynaptic density) had disappeared. There was also a loss of complex spines and some shrinkage of the molecular layer.

Animals↗
PubMed1976

An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts.

Intact synapses in the denervated area of the rat dentate gyrus are reduced to 14% of those normally present 2-4 days following a unilateral entorhinal lesion. By 160-240 days after lesion, the former entorhinal terminal zone is repopulated with new synapses. In all, there is more than a 5-fold increase in the density of intact synapses in the denervated zone between 2 and 240 days post-lesion, and the denervated zone of the molecular layer is restored to 80% of control values. The synapses are Gray type I and are formed on simple and complex spines which closely resemble those normally present. A few boutons have an abnormally large number of synaptic junctions. Reinnervation seems to progress at differential rates. Synapses are rapidly regained up to 30 days after operation, but thereafter the reacquisition of synaptic connections is much slower. Reinnervation is more rapid in the portion of the denervated zone nearest the granule cells, where the maximal densities are attained within 30 days. The time course of reinnervation differed from that of degeneration. A portion of the new synapses in the reinnervated molecular layer appear to arise by the assembly of new synaptic junctions. Over time, the number of post-synaptic contact sites along a given length of dendritic surface recovers, suggesting the formation of new synaptic sites. Our data indicate that granule cells retain a capacity even into adulthood to manufacture, position and assemble postsynaptic components of a synapse and, in concert with reactive afferents, form normal-appearing synapses.

Animals↗
PubMed1975

X-ray crystallographic study of boronic acid adducts with subtilisin BPN' (Novo). A model for the catalytic transition state.

We have studied the structures of adducts formed between subtilisin BPN' and both benzeneboronic acid and 2-phenylethaneboronic acid by x-ray diffraction techniques. Electron density and difference maps at 2.5 A resolution were computed with phases calculated from a partially refined structure of the native enzyme (R = 0.23 at 2.0 A). Both adducts contain a covalent bond between Ogamma of the catalytic Ser-221 and the inhibitor boron atom. The boron atom is coordinated tetrahedrally, with one of the two additional boronic acid oxygen atoms lying in the "oxyanion hole" and the other at the leaving group site identified in previous studies (ROBERTUS, J.D., Kraut, J. ALDEN, R.A., and BIRKTOFT, J.J. (1972) Biochemistry 11, 4293-4303). Moreover, the previously postulated structure of the tetrahedral intermediate for substrate hydrolysis is isosteric with these boronic acid adducts, which can therefore be considered good models for the transition state complex (KOEHLER, K.K., and LIENHARD, G.E. (1972) Biochemistry 10, 2477-2483). These observations further support the suggestion that an important contribution to stabilization of this transition state complex, relative to both the Michaelis complex and the acyl intermediate, occurs as a consequence of hydrogen bond donation to the substrate carbonyl oxygen atom from the side chain amido group of Asn-155 and from the backbone amido group of Ser-221.

Binding Sites↗
PubMed1973

Synaptic rearrangement in the dentate gyrus: histochemical evidence of adjustments after lesions in immature and adult rats.

In immature animals, ablation of the entorhinal cortex elicited a rapid intensification of acetylcholinesterase (EC 3.1.1.7) staining in the outer one-quarter of the molecular layer of the dentate gyrus. Subsequent lesions of the septum eliminated this acetylcholinesterase intensification. Electron-microscopic histochemical analysis demonstrated a 30-fold increase in the number of acetylcholinesterase-positive synaptic endings in the intensification zone. The acetylcholinesterase augmentation thus appears attributable, in part at least, to an increase in the number of acetylcholinesterase-rich synaptic endings established by septo-hippocampal fibers. Observations in a comparative study of immature and adult rats point to the animal's developmental state as a major determinant of differences in these lesion-induced neuronal adjustments.

Acetylcholinesterase↗
PubMedDate not supplied

Religious commitment and health status: a review of the research and implications for family medicine.

The empirical literature from epidemiological and clinical studies regarding the relationship between religious factors (eg, frequency of religious attendance, private religious involvement, and relying on one's religious beliefs as a source of strength and coping) and physical and mental health status in the areas of prevention, coping, and recovery was reviewed. Empirical studies from the published literature that contained at least 1 measure of subjects' religious commitment and at least 1 measure of their physical or mental health status were used. In particular, studies that examined the role of religious commitment or religious involvement in the prevention of illness, coping with illnesses that have already arisen, and recovery from illness were highlighted. A large proportion of published empirical data suggest that religious commitment may play a beneficial role in preventing mental and physical illness, improving how people cope with mental and physical illness, and facilitating recovery from illness. However, much still remains to be investigated with improved studies that are specially designed to investigate the connection between religious involvement and health status. Nevertheless, the available data suggest that practitioners who make several small changes in how patients' religious commitments are broached in clinical practice may enhance health care outcomes.

Adaptation, Psychological↗
PubMedDate not supplied

Medical subspecialty training and interest in cost containment education.

To investigate academic physicians' interest in learning methods to reduce health care costs, we asked the faculty and housestaff of a university-based department of internal medicine to rate their interest in 30 potential topics for medical grand rounds, a traditional forum for continuing medical education. The 30 topics were equally divided among clinical, research and cost-containment categories. The 29 housestaff and the 41 subspecialty faculty members clearly favored clinical and research topics over cost-containment topics (p less than 0.001). On the other hand, the nine general internists considered the cost-containment topics as attractive as the clinical and research topics and ranked them higher than did both the subspecialists (p less than 0.001) and the house-staff (p less than 0.05). Efforts to alter costs in academic medical centers may be hampered by the relative disinterest in cost-containment education among house officers and subspecialists, who are responsible for most of the health care delivery in this setting.

Attitude of Health Personnel↗
PubMedDate not supplied

A new instrument for patients' ratings of physician performance in the hospital setting.

A new instrument to elicit patients' appraisals of physician performance has been developed from a previously-derived taxonomy of desired physician attitudes and behavior. The instrument allows patients to give ratings for their physicians' discrete, observable items of behavior, and also for complex, multidimensional attributes. When the instrument was administered to 131 randomly chosen medical inpatients, the results showed that technical competence and interpersonal (or humanistic) qualities were equally valued, and that physicians received high ratings for most features of performance. Except for less satisfaction in younger patients, clinical and demographic characteristics had little impact on the ratings. The performance characteristics of the instrument appear satisfactory, and its potential applications and proposals for further research are discussed.

Clinical Competence↗
PubMedDate not supplied

Depression among patients with a chief complaint of chronic fatigue.

The prevalence of mood disorders among patients with chronic fatigue was examined in a group of 100 adults who had experienced fatigue symptoms for an average of 13 years. Patients received a comprehensive history, physical and laboratory evaluation and completed the National Institute of Mental Health Diagnostic Interview Schedule and the Beck Depression Inventory (BDI). Among 44 patients with depressive illness, the onset of their first depressive episode was strongly associated with and preceded the onset of chronic fatigue. The BDI, fatigue history, demographic factors, and findings from the physical examination and laboratory had only modest success in discriminating those patients with depressive illness from other patients. We conclude that depressive illness is an important precursor of chronic fatigue.

Adult↗
PubMedDate not supplied

Responses of Onondaga Lake, New York, to early stages of rehabilitation: unanticipated ecosystem feedbacks.

Responses of polluted Onondaga Lake, New York, to early stages of a phased program to rehabilitate the lake from the effects of domestic waste inputs are documented. The analysis is based on more than 10 years of paired monitoring of the effluent (total ammonia and total phosphorus) of a wastewater treatment plant (WWTP) that discharges to the lake as well as the lake itself (including total ammonia, nitrite, total and dissolved forms of phosphorus, plankton biomass and composition, Secchi disc transparency, and zebra mussel density). Major reductions in total ammonia and total phosphorus loading relative to the preceding decade are reported for the WWTP for the November 1998 through October 1999 interval. Dramatic and, in some cases, unanticipated changes in the lake's water quality and biota in response to the reductions in loading are documented for the April to October interval of 1999 including: (1) major decreases in total ammonia concentrations and improved status with respect to ammonia toxicity standards, (2) development of dense populations of zebra mussels, (3) decreases in fall concentrations of nitrite and improved status with respect to the related toxicity standard, (4) decreases in total phosphorus and total dissolved phosphorus concentrations, and (5) a severe Microcystis (phytoplankton) bloom that caused nuisance conditions and poor clarity. The zebra mussel invasion is attributed to the reductions in total ammonia concentrations to below toxic levels. The Microcystis bloom was probably related to the abrupt increase in the zebra mussel population. Additional reductions in phosphorus loading from the WWTP will be required to limit phytoplankton production and avoid the potential for continued nuisance conditions. Potential complications in resolving lake responses to future reductions in loading associated with the zebra mussel invasion are considered.

Animals↗