Understanding the psychosocial challenges of older adulthood.
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Biomedical subjects
Publications and source records attributed to C A Miller.
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This study documents the light-microscopic and ultrastructural characteristics of ganglion cell degeneration in the retinas of patients with Alzheimer's disease (AD). The results show degeneration in the retinal ganglion cells (RGCs) characterized by a vacuolated, 'frothy' appearance of the cytoplasm. The degeneration is unique in AD because of the absence of neurofibrillary tangles within the RGCs, or of neuritic plaques or amyloid angiopathy in the retinas or optic nerves of any of the cases examined. These results suggest that neuronal degeneration in the ganglion cell layer (GCL) should be added to the constellation of neuropathologic changes found in patients with Alzheimer's disease.
Deoxyhemoglobin S fibers associate into bundles, or fascicles, that subsequently crystallize by a process of alignment and fusion. We have used electron microscopy to study the formation of fascicles and the changes in fiber packing that occur during the conversion of fascicles to crystals. The first event in crystallization involves fibers forming fascicles that are initially small and poorly ordered but, with time, become progressively larger and more highly ordered. After six to eight hours, the fibers in a fascicle form a crystalline lattice. The three-dimensional unit cell parameters of this lattice are a = 1300 A, b = 365 A, and c = 210 A (the a axis is parallel to the fiber axis). Fibers have an elliptical cross-section whose major and minor axes are 250 A and 185 A, respectively. When projected on to the unit cell vectors, these dimensions are 210 A and 155 A, so the unit cell dimension of 365 A implies that there are two fibers per unit cell. Theoretically, fibers could pair so that each member of the unit cell is oriented in the same direction (parallel) or opposite directions (antiparallel). Fourier transforms of electron micrographs (or models) cannot distinguish between these alternatives, since the two arrangements produce very similar intensity distributions. The orientation of the fibers was determined from cross-sections of the fascicles in which the fibers are seen end-on. In this view the images of the fibers are rotationally blurred because the fibers twist 30 degrees to 40 degrees about their helical axis through the 300 A to 400 A thick section. We have been able to remove the rotational blur from each of the fibers in the unit cell using the procedures described by Carragher et al. The deblurred images of the two fibers in the unit cell are related by mirror symmetry. This relationship means that the fibers are antiparallel. These observations suggest that crystallization of fibers in fascicles is mediated by assembly of the fibers into antiparallel pairs that contain equal numbers of double strands running in each direction.
Monoclonal antibodies (MAbs) are useful for the identification of nervous system antigens localized to neuronal subpopulations. We have examined the transport of the corresponding antigens of four such MAbs in guinea pig retinal ganglion-cell axons. Determination of the axonal transport rate of radiolabeled antigens allowed their assignment to one of the three major anterograde axonal transport rate components, each of which is through to convey a subcellular structural system in the axon. Antigens identified by three of the MAbs were found to be transported in slow component b of axonal transport, the component thought to convey the cytoplasmic matrix, and an antigen identified by the fourth MAb was found in slow component a, similarly thought to contain the linear cytoskeletal elements. Assignment of these antigens to the different rate components suggests that they may be associated with a particular structural system in neurons. Additionally, in cases where more than one nervous system cell type may express a particular antigen, the identity of the neuronal form of the antigen has been confirmed by its axonal transport. The roles that these antigens may play in the nervous system during normal axonal function and during neuropathogenesis can now be further examined.
Although the use of shunts for carotid artery surgery remains controversial, the hemodynamics of the shunts currently available have not been carefully evaluated in vivo. We developed an animal model using contralateral carotid artery ligation, which produced ipsilateral carotid blood flows (640 +/- 44 ml/min) and internal carotid stump pressures (52 +/- 4 mm Hg) over a range commonly seen in carotid artery surgery. Seven shunts were tested and included Javid; 10F and 8F Brener; and 14F, 12F, 10F, and 8F Argyle shunts. The hemodynamic features evaluated for each shunt included maximum shunt flow, the pressure gradients occurring across each shunt, the increase in cerebral perfusion pressure over occlusion pressure associated with shunt placement, and the distal pressure pulse waveform. The larger diameter shunts were consistently better than the smaller diameter shunts. The correlation between shunt flow and the increase in distal pressure produced by shunt placement was high (r = 0.98, p less than 0.05), confirming that high flow rates maintained high perfusion pressure. By relating maximum shunt flow and the pressure gradient to the change in the pressure pulse contour for each shunt, it could be demonstrated that at the larger diameters, straight shunts displayed superior hemodynamic characteristics compared with tapered shunts, whereas at smaller diameters, tapered shunts were superior.
In an effort to determine whether the population of patients undergoing isolated coronary artery bypass grafting and the outcome of these operations have changed, we analyzed the records of two patient populations from our institution. Interventional cardiology techniques (angioplasty, thrombolysis) were not used at our institution before 1982. The records of 736 patients (group 1) who underwent isolated coronary artery bypass grafting from January 1975 to July 1981 were reviewed and compared with a group of 603 patients (group 2) who underwent operation from July 1985 to December 1987. The techniques of operation and myocardial preservation were virtually identical during the two periods. During the group 2 analysis period, 343 angioplasty procedures were performed. The patients in group 2 were significantly older, had increased preoperative New York Heart Association classification, had sustained more previous myocardial infarctions, and had more associated morbid medical conditions. There was a threefold increase in patients seen for reoperative revascularization procedures and a fourfold increase in emergency operations. Overall mortality, although not significantly different, did increase slightly from 2.69% in group 1 to 3.83% in group 2. Mortality after elective procedures remained essentially unchanged (2.05% for group 1 and 1.90% for group 2).
Low cardiac output after heart surgery occurs more frequently in infants than in adults. This study was designed to determine whether this finding could be explained by a greater susceptibility of the immature heart to ischemia. An isolated working heart model was used to compare myocardial recovery in sets of hearts from six immature (2 weeks, 500 g) and six mature (20 weeks, 2 kg) rabbits after 10, 20, and 30 min of ischemia at 37 degrees C. Mean aortic pressure (MAP), aortic flow (AF), heart rate (HR), left atrial pressure (LAP), and ATP and glycogen levels were measured before and after ischemia. Hemodynamic results are expressed as the percentage recovery of preischemic values. ATP and glycogen are reported as micrograms per gram dry weight. After each period of ischemia, the immature hearts had superior recovery of AF (95 +/- 7.0, 72 +/- 8.8, 70 +/- 7.5 vs 58 +/- 7.1, 34 +/- 15.5, 13 +/- 9.1, P less than 0.05). After 10 min of ischemia, recovery of MAP was not different (97 +/- 1.5 vs 100 +/- 3.5), but after 20 and 30 min of ischemia, the immature hearts had better recovery of MAP (108 +/- 10.8, 98 +/- 5.4 vs 64 +/- 10.8, 48 +/- 6.0, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
A select group of non-histone proteins becomes complexed to DNA after Chinese hamster ovary (CHO) cells are treated with potassium chromate. The most abundant complexed protein has a mol. wt of approximately 45 kd and is thought to be actin. An antiserum to the chromate-induced DNA-protein complexes (DPCs) was prepared to facilitate the study of these complexes. Rather than detecting the predominant silver-stained proteins of DPCs described in an earlier study, this antiserum reacts primarily with an acidic 95-kd protein (p95) that does not silver stain. The antiserum can be used routinely to assay for the induction of p95-DNA complexes produced by chromate and perhaps by other carcinogens. Immunofluorescent staining of CHO cells and immunoblotting of cell fractions show the reactive antigens are within the cell nucleus. Blotting experiments with the antiserum indicate the chromate-induced p95-DNA complex dissociates in the presence of 2-mercaptoethanol, suggesting similarity to the DPCs formed by carcinogenic platinum compounds. A reduced species of chromium (probably Cr3+) may form DPCs by binding to the nitrogen, oxygen or sulfur atoms of proteins and DNA. These results illustrate the usefulness of immunological detection methods to study specific DNA-protein interactions induced by carcinogens. The possible relevance of DPCs in the carcinogenic process is discussed.
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Public health nurses and other professional and paraprofessional workers have engaged in prenatal home visiting for many decades. Yet, the extent to which this and other prenatal interventions influence maternal behavior is largely unknown. This study was undertaken to collect and categorize perceptions of experts in the organization and delivery of prenatal care about the value of selected strategies for encouraging participation in care, for education, and for changing behavior, with special emphasis on home visiting. The survey sample consisted of 151 experts who were identified by directors of maternal and child health programs in 48 of the 50 states. One hundred eighteen of the experts, almost half of whom were nurses, responded to the survey. The findings suggest important discrepancies between respondents' perceptions about the effectiveness of some prenatal strategies and the actual extent of their use in practice. In addition, the results raise questions about the appropriate mix of type of home visitor and purpose of visit. These questions should form the basis for subsequent investigations.
Monoclonal antibody 44.1, an immunocytochemical marker for neurons, identified heterotopically located, multipolar neurons deep within the spinal cord white matter of patients with amyotrophic lateral sclerosis. Displaced neurons were most numerous in the ventral outflow and lateral corticospinal tract regions of all cord levels. These changes may be the result of aberrant neuronal migration during spinal cord development.
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1. Assessment of older adults with behavior problems considers factors contributing to the behavior; potential psychosocial interventions; patient characteristics influencing medication action; and medication characteristics influencing therapeutic and adverse effects. 2. Anxiety, agitation, and other behavioral problems in demented patients might arise from their inability to verbally express complaints such as pain and discomfort. 3. Although constant blood levels of medication are most effective for ongoing management of behavior problems, as needed doses can be used to establish the optimal dosing schedule. 4. Medications in low doses can be used to improve the patient's response to psychosocial interventions for behaviors such as anxiety, agitation, depression, and sleep disorders; but they should not be used as the only intervention.
The proteins cross-linked to the DNA of cultured Chinese hamster ovary cells after exposure to cis-diamminedichloroplatinum(II) (cis-Pt), chromate, and formaldehyde were compared by two-dimensional (2D) gel electrophoresis, immunoblotting, and centrifugal assays that measured cross-link stability. Chromate and cis-Pt cross-linked seven of the same nonhistone proteins, such as actin, to DNA. In contrast, formaldehyde selectively formed histone-DNA cross-links. Immunoblotting experiments showed that all three chemicals cross-linked a 97-kDa nuclear protein to the DNA despite their different chemical reactivity with DNA and proteins. The chromate- and cis-Pt-induced cross-links were disrupted by thiourea, 2-mercaptoethanol, and EDTA, indicating that the metal could be chemically displaced from the cross-links. The formaldehyde-induced complexes required degradation with DNase 1 for the resolution of histones on 2D gels and were not chemically labile like the metal-induced cross-links. The agents and methodology used here could be applied to the study of additional nuclear proteins that bind or reside near the DNA.
Monoclonal antibody probes were used to identify antigenic cross reactivities among neuronal subpopulations and to dissect the human nervous system at several levels of organization. Six monoclonal antibodies, prepared with immunogens from Drosophila melanogaster or human nervous tissue, were used to localize antigens immunocytochemically in normal adult human neocortex, hippocampus, cerebellum, spinal cord, and retina. Four of the six antibodies were neural specific in their reactivity and each stained a unique combination of neurons. The antibodies reacted with at least three subpopulations of cerebral cortical neurons, including discrete populations of pyramidal and nonpyramidal cells. Components of a widely distributed functional system within the spinal cord and cerebellum were labelled by one antibody, which reacted with neurons in the nucleus dorsalis of Clarke, deep cerebellar nuclei, and Purkinje cells. At the single-cell level, three of the monoclonals differentially labelled the photoreceptor cell outer segment, inner segment, and perikaryon. Three of the six antibodies were reactive with specific protein bands on immunoblots of tissue homogenates. This monoclonal antibody panel provides a novel and potentially useful method of analysis of the organization of the normal and diseased human nervous system.
Potassium chromate induced the formation of DNA-protein complexes in cultured Chinese hamster ovary cells. The DNA-protein complexes were isolated by ultracentrifugal sedimentation in the presence of 2% sodium dodecyl sulfate (SDS) and 5 M urea. Two-dimensional SDS-polyacrylamide gel electrophoresis analysis of the chromate-induced DNA-protein complexes revealed that two acidic proteins of 53 and 45 kDa and a basic protein of 54 kDa were selectively complexed to the DNA. Numerous other proteins also became associated with the DNA to a lesser degree as the chromate concentration was increased. Nuclease digestion was not a prerequisite for the resolution of the protein component of the DNA-protein complexes using two-dimensional gel electrophoresis. Ultracentrifugal analysis of the DNA-protein complexes in the presence of proteinase K, nucleases, or a chelating agent demonstrated that protein aggregation was not responsible for the increased protein recovery in chromate-treated samples and that the complexes were disrupted by EDTA. These data suggest that the selectively complexed proteins were associated with the DNA through strong interactions that may be mediated by the trivalent form of chromium.
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