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Biomedical subjects

R Terry

Publications and source records attributed to R Terry.

At least 19 recordsLinked to original sources

Localization of amyloid precursor protein in GAP43-immunoreactive aberrant sprouting neurites in Alzheimer's disease.

Previous in vitro studies have suggested that amyloid precursor protein (APP) could be involved in cell surface adhesion, neuritic growth and survival of hippocampal neurons. In the present study, involvement of APP in aberrant sprouting in Alzheimer's disease (AD) was studied by comparing immunolabeling patterns of anti-APP and anti-growth-associated protein 43 (anti-GAP43). Confocal laser imaging of frontal cortex sections double-immunolabeled for APP and GAP43 showed an increase, in AD, of presynaptic boutons immunostained with anti-GAP43 that contained anti-APP immunoreactivity. The neuritic plaques in AD cases presented intense anti-GAP43 immunoreactive abnormal neurites colocalized with anti-APP. Three-dimensional reconstruction of the plaques showed that anti-APP was colocalized with anti-GAP43 in 57.5% of the aberrant sprouting neurites. We conclude that co-expression of APP with GAP43 in the plaque might be involved in the aberrant sprouting response observed in AD.

Aged

Predicting early adolescent disorder from childhood aggression and peer rejection.

Two large cohorts of Black 3rd-grade children from low-income families were followed into early adolescence. Adjustment at the end of the 1st year of middle school was assessed by teacher and parent ratings and by adolescent self-reports. Childhood peer social status predicted parent-reported externalized and internalized disorder and self-reported internalized disorder. Childhood aggression predicted self-reported externalized and internalized disorder and parent-reported externalized disorder. Teacher ratings of school adjustment were predicted by aggression, rejection, and sex of the child. Consensus judgments of poor adjustment were predicted by both aggression and peer rejection, with sex moderating the effect of peer rejection. Both childhood aggression and peer rejection appear to be significant predictors of adolescent disorder, with each making a predictive contribution uniquely its own.

Adolescent

Hippocampal grafts into the intact brain induce epileptic patterns.

Spontaneous hippocampal EEG activity and evoked field potentials were investigated in intact rats and in animals with fetal hippocampal grafts. Pieces of hippocampal grafts, derived from 15- to 16-day-old fetuses, were used to prepare cell suspensions and grafted directly into the intact hippocampus. Control animals received suspension grafts of the cerebellum derived from fetuses of identical age. Host hippocampal electrical patterns were monitored with chronic single electrodes or with a 16-microelectrode probe from 7 to 10 months after grafting. In contrast to previously reported high survival rates of fetal grafts in studies with damage to the host brain prior to grafting, survival of both hippocampal (60%) and cerebellar grafts (20%) was very poor in the intact hippocampus. In animals with cerebellar transplants or without surviving grafted neurons the electrical activity of the host hippocampus was indistinguishable from normal controls. In rats with hippocampal grafts short duration, large amplitude EEG spikes (up to 10 mV) were recorded, predominantly during immobility. When the EEG spikes (putative interictal spikes) were of large amplitude and contained population spikes, test evoked responses delivered to the perforant path were suppressed after the spontaneous events. In contrast, evoked responses were facilitated by interictal spikes without population spikes. The threshold of electrically induced afterdischarges did not differ significantly between groups of intact rats and animals with or without hippocampal grafts. However, in three rats with hippocampal grafts the evoked afterdischarges were associated with behavioral seizures. In two of these rats spontaneously occurring seizures were also observed. Synaptophysin-immunoreactivity demonstrated growth of the host mossy fibers into the graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase

Late onset dementia with argyrophilic grains and subcortical tangles or atypical progressive supranuclear palsy?

Most clinically demented elderly patients are found at autopsy to have Alzheimer's disease, multi-infarct dementia, Parkinson's disease, Pick's disease, or Creutzfeldt-Jakob disease. We studied 5 patients clinically characterized by late onset dementia whose brains showed no pathological evidence of Alzheimer's disease, or any other specific neuropathological diagnosis. We found argyrophilic grains, coiled bodies, abundant Alz-50-positive and thioflavine S-negative neurofibrillary tangles, and neuropil threads in the hippocampus, entorhinal cortex, locus ceruleus, substantia nigra, subthalamic nucleus, and inferior olives. Ultrastructurally, the grains, threads, and tangles were composed of straight tubulofilamentous structures, 25 nm in diameter, similar to those found in patients with progressive supranuclear palsy but different from the paired helical filaments of patients with Alzheimer's disease. These findings suggest that the late onset dementia with argyrophilic grains syndrome is also characterized by the presence of tangles and threads with the topographical distribution of progressive supranuclear palsy.

Aged

Neocortical damage during HIV infection.

Clinical and pathological evidence of subcortical central nervous system (CNS) damage is observed commonly in patients with human immunodeficiency virus (HIV) encephalitis. Whether other CNS regions are also affected has not been well studied. We report neocortical damage in patients with HIV encephalitis. Using quantitative techniques, we demonstrate statistically significant thinning of the neocortex, with a loss of large cortical neurons. Qualitative and quantitative assessments of neocortical neuropil reveal a loss of synaptic density and vacuolation of dendritic processes. Failure to demonstrate an association of these changes with the presence of HIV antigens suggests that neocortical damage may be an indirect effect of HIV infection of the CNS.

AIDS Dementia Complex

Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in Alzheimer's disease.

Both protein kinases and phosphoprotein phosphatases are important components of signal transduction systems in cells. Recent studies in Alzheimer's disease (AD) have shown abnormal protein phosphorylation in the cortex suggesting an alteration in these enzymes. In the present study, an antibody against CD45 was used to analyze the status of this protein phosphotyrosine phosphatase in AD. We studied and quantified the immunohistochemical and immunochemical distribution of this integral membrane protein in control and AD brain. We found that anti-CD45 immunostained the great majority of microglia, both resting and activated. These cells were Ricinus communis agglutinin I positive and glial fibrillary acidic protein and neurofilament negative. The AD frontal cortex showed a 35% (P less than 0.01) increase in the number of anti-CD45 immunoreactive microglia as compared with controls. These results were consistent with the immunoblot quantification of CD45 immunoreactivity following native gel electrophoresis. In AD, 30% of the CD45-immunostained microglia were clustered in the neuritic plaques (about six per plaque) while the remaining 70% were scattered in the neuropil. The AD hippocampus showed an increase in CD45-immunoreactive microglia in the molecular layer of the dentate gyrus. At the ultrastructural level, CD45 immunoreactivity was localized exclusively to the plasma membrane of the microglia. The presence of the anti-CD45 immunoreactivity in microglia suggests the possibility that they may require the presence of CD45 as a cell surface receptor which may regulate cell function through modulation of intracellular signaling.

Aged

Patterns of aberrant sprouting in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by extensive synaptic and neuronal loss and by plaque formation in the cortex, but the mechanisms responsible for synaptic plasticity in the neocortex are still not completely understood. To analyze the sprouting response in AD cortex, we compared the patterns of GAP-43 with synaptophysin immunoreactivity. In AD, GAP-43 immunohistochemistry revealed extensive sprouting in the hippocampal molecular layer, stratum polymorphous, CA1 region, and prosubiculum. These regions presented abundant anti-GAP-43-immunoreactive coiled fibers and dystrophic neurites in association with plaques. Some of these sprouting structures were colocalized with anti-synapto-physin- and anti-neurofilament-positive neurites. The AD neocortex was characterized by an overall decrease in GAP-43 immunoreactivity accompanied by sprouting neurites in the areas of synaptic pathology. We conclude that GAP-43 might be involved in the mechanisms of synaptic plasticity in the AD cortex, as well as in the process of aberrant sprouting in the neuritic plaques.

Aged

The role of aggression in peer relations: an analysis of aggression episodes in boys' play groups.

Although aggression is frequently cited as a major cause of peer social rejection, no more than half of all aggressive children are rejected. Aggressive episode data from experimental play groups of 7- and 9-year-old black males were coded to examine whether qualitative aspects of aggressive behavior, as well as frequency of aggression, determine the relation between aggressiveness and peer rejection. Reactive aggression and bullying were related to peer status among 9-year-olds, but not 7-year-olds, whereas instrumental aggression was characteristic of highly aggressive, rejected boys at both ages. Qualitative features of aggressive interaction suggested a greater level of hostility toward peers and a tendency to violate norms for aggressive exchange among rejected, aggressive boys at both ages in contrast to other groups of boys. The descriptive data provide a distinctive picture of reactive, instrumental, and bullying aggression as well as differing social norms for target and aggressor behavior in each of these 3 types of aggression.

Age Factors

An implantable neurocybernetic prosthesis system.

The neurocybernetic prosthesis (Cyberonics, Inc.) is an implantable, multiprogrammable pulse generator that delivers constant current electrical signals to the vagus nerve for the purpose of reducing the frequency and/or severity of epileptic seizures. The device is implanted in a subcutaneous chest pocket just below the clavicle, similar to cardiac pacemaker placement. The stimulation signal is transmitted from the prosthesis to the vagus nerve through a stimulation lead. The prosthesis can be programmed using any IBM-compatible personal computer with programming software and a programming wand. The electrodes used in the first group of patients were found to break at an unacceptable rate. Design modifications appear to have resolved this problem.

Animals

Memory sources of REM and NREM dreams.

Sixteen male volunteers slept 4 nonconsecutive nights each in a sleep laboratory. They were awakened for one dream report per night. Awakenings were made, in counterbalanced order, from early-night and late-night rapid-eye movement (REM) and non-REM (NREM) sleep. Following dream reporting, subjects were asked to identify memory sources of their dream imagery. Two independent judges reliably rated mentation reports for temporal units and categorized memory sources as autobiographical episodes, abstract self-references, or semantic knowledge. We replicated earlier findings that semantic knowledge is more frequently mentioned as a dream source for REM than for NREM reports. However, with controls for length of reports, the REM-NREM difference disappeared, indicating that the stage difference in memory sources was not independent of stage difference in report lengths. There was a significant effect of time of night on source class, but only in REM sleep: Both without and with controls for report length, more semantic sources were cited for late than for early REM dreams.

Adult

Thalamic nuclei in Alzheimer disease: evidence against the cholinergic hypothesis of plaque formation.

Recent studies provide evidence for a significant cholinergic projection from the nucleus basalis of Meynert (NbM) to the reticular and mediodorsal thalamic nuclei. We examined the incidence and distribution of plaques in the thalamus in order to determine whether in Alzheimer's disease degenerating cholinergic processes from the NbM induce the emergence of plaques according to the cholinergic hypothesis. The present study shows that degeneration of NbM neurons does not induce plaques in the thalamic nuclei it innervates, and that plaques appear more frequently in other thalamic nuclei that do not receive projections from the NbM.

Alzheimer Disease

Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques.

Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy-eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age-matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plaques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (greater than 90 micron 2 in a cross-sectional area in cerebral cortex) as compared to age-matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve.

Aged

Properties of avian sarcoma-leukosis virus pp32-related pol-endonucleases produced in Escherichia coli.

The gag-pol precursor protein of the avian sarcoma-leukosis virus is processed into three known pol-encoded mature polypeptides; the 95- and 63-kilodalton (kDa) beta and alpha subunits, respectively, of reverse transcriptase and the 32-kDa pp32 protein. The pp32 protein possesses DNA endonuclease activity and is produced from the precursor by two proteolytic cleavage events, one of which removes 4.1 kDa of protein from the C terminus. A 36-kDa protein (p36pol) which retains this C-terminal segment is detectable in small quantities in virions. We have constructed Escherichia coli plasmid clones that express the C-terminal domains of pol corresponding to pp32 and p36. These proteins have been purified by column chromatographic methods to near homogeneity. No significant differences could be detected in the enzymatic properties of the bacterially produced p32pol and p36pol proteins. Both possess DNA endonuclease activity and, like the pp32 protein isolated from virions, can cleave near the junction of two tandem avian sarcoma-leukosis virus long terminal repeats in double-stranded supercoiled DNA substrates. In the presence of Mg2+, both p32pol and viral pp32 cleave either strand of DNA 2 nucleotides 5' to the junction.

Amino Acid Sequence

Nifedipine gastrointestinal therapeutic system in stable angina pectoris. Results of a multicenter open-label crossover comparison with standard nifedipine.

To compare the clinical efficacy and dose equivalency of standard nifedipine versus a new gastrointestinal therapeutic system (GITS) formulation of nifedipine, 98 patients with chronic stable angina pectoris participated in a 14-week, multicenter, open-label, crossover trial. All patients were administered nifedipine capsules for one month prior to study entry and continued receiving other antianginal, non-calcium blocker medications. Ninety-one patients (93 percent), 80 men and 11 women, mean age 62 +/- 1 years, completed the trial, which included two weeks receiving standard nifedipine followed by 12 weeks receiving nifedipine GITS starting at a dosage equal to the 24-hour total dose of nifedipine capsules and titrated upward as necessary. However, throughout the trial, mean nifedipine dosage was similar on nifedipine GITS compared with standard nifedipine. Angina frequency was significantly less with nifedipine GITS at Weeks 6, 10, and 14 (0.8 episodes/week) compared with baseline with standard nifedipine (1.3 episodes/week, p less than 0.05). Likewise, nitroglycerin consumption was also less at Weeks 6, 10, and 14, but only significantly less at Week 6 (nifedipine 1.2/week versus nifedipine GITS at six weeks, 0.7/week; p less than 0.05). Resting hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, were not significantly different with standard nifedipine versus nifedipine GITS during the 12-week study. Total incidences of side effects were similar for both treatments (standard nifedipine, 16; nifedipine GITS, 17). However, incidence of vasodilator side effects (flushing, dizziness, and light-headedness) was significantly less frequent with nifedipine GITS (standard nifedipine, 12; nifedipine GITS, six; p less than 0.05). Thus, results from this open-label, crossover trial suggest that nifedipine GITS dosing is similar to multidose standard nifedipine with equivalent 24-hour efficacy for nifedipine GITS.

Aged

Avian sarcoma and leukosis virus pol-endonuclease recognition of the tandem long terminal repeat junction: minimum site required for cleavage is also required for viral growth.

Integration of retroviral DNA is a site-specific reaction involving an endonuclease encoded by the viral pol gene (pol-endo). In vitro the pol-endo from avian sarcoma and leukosis viruses (ASLVs) cleaves both DNA strands near the U5-U3 junction of tandem long terminal repeats (LTR-LTR junction) in single-stranded and replicative form (RF)-I substrates. We have reported previously that the sequences that are required for cleavage of single-stranded substrates by the alpha beta form of the pol-endo differ for the plus and minus strands (G. Duyk, M. Longiaru, D. Cobrinik, R. Kowal, P. deHaseth, A. M. Skalka, and J. Leis, J. Virol. 56:589-599, 1985). This is not the case with RF-I substrates, in which a maximum of 22 base pairs of U5 and 8 base pairs of U3 were required for alpha beta pol-endo cleavage in each strand. Insertion of a palindromic octanucleotide (CATCGATG) at the LTR-LTR junction abolished cleavage in RF-I but not in single-stranded DNA substrates. Deletion of the four nucleotides (TTAA) at the junction prevented cleavage in the plus strand of RF-I DNA, but did not affect cleavage of single-stranded DNA. Furthermore, the alpha beta form of ASLV pol-endo did not recognize heterologous LTR-LTR junction sequences from the reticuloendotheliosis virus or Moloney murine leukemia virus in either substrate form, despite their sequence and structural similarities to the ASLV junction. These results support a role for a sequence-specific interaction between the ASLV pol-endo and the LTR-LTR junction domains that are required for cleavage. By using the infectious Rous sarcoma virus clone pATV8-K, we introduced a set of deletions into the U5 region that would be incorporated into the LTR-LTR junction on viral replication. In the unintegrated provirus, the deletions started 43 base pairs from the LTR-LTR junction and extended various lengths toward the junction. Results of transfection studies with these clones indicated that the U5 sequences that are required for virus production in vivo correspond to those that are required for cleavage of RF-I DNA in vitro.

Alpharetrovirus