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R R Johnson

Publications and source records attributed to R R Johnson.

At least 19 recordsLinked to original sources
PubMed1997

A polysynaptic feedback circuit in rat visual cortex.

Feedback connections from extrastriate cortex to primary visual cortex (V1) in the primate may provide "top-down" information that plays a role in visual attention and object recognition. Our work in a rodent model of corticocortical circuitry demonstrates that feedback pathways synapse preferentially with pyramidal cells in V1 () and favor excitation over inhibition in cortical microcircuits (). To investigate the polysynaptic circuits activated by feedback inputs, we studied chains of neurons postsynaptic to feedback connections using a combination of axonal tract tracing and anterograde degeneration. This approach enabled independent labeling of local collaterals of forward-projecting neurons in V1 and feedback connections from extrastriate lateromedial (LM) visual area to V1. Postsynaptic targets were identified in the electron microscope after retrograde transport of biotinylated dextran amine (BDA) to identify dendrites of forward-projecting neurons (i.e., from V1 to LM) and postembedding immunogold labeling to identify GABAergic interneurons. The results show that feedback connections provide strong monosynaptic input to forward-projecting neurons in V1. These neurons in turn make local connections that preferentially form synapses with other pyramidal cells ( approximately 97%), many of which were identified as forward-projecting neurons. This indicates that feedback pathways provide input directly to neurons which make the reciprocal forward connection, and that feedback-recipient forward-projecting neurons are strongly interconnected. The function of these excitatory networks within V1 may be to amplify feedback activity and provide a circuit for modulation of striate cortical activity by top-down influences.

Animals↗
PubMed1997

Breast care consultation center: role of the pathologist in a multidisciplinary center.

The Breast Care Consultation Center (BCCC) is a multidisciplinary center providing, in a single setting, a complete outpatient facility for women who have been diagnosed with or suspected of having breast cancer. A team of specialists are available to provide comprehensive, diagnostic (radiologist, surgeon, and pathologist), therapeutic (surgeon, radiotherapist, and medical oncologist), and support options. The pathologist, as a member of the diagnostic team, evaluates the material obtained or received at the BCCC. These include fine-needle aspirations (FNAs) obtained on-site as well as previously prepared cytohistological specimens. The pathologist renders the diagnosis following examination of the material and consultation with the multidisciplinary team. Thus, this approach is conducive for appropriate and accurate diagnosis where all data are available. In addition, the pathologist discusses the findings of each patient in the multidisciplinary conference. One thousand four hundred eighteen patients were evaluated at Magee-Womens Hospital BCCC from February 1992 through December 1994, during which time 366 FNAs were performed. The accuracy for positive diagnosis was 100%. Six negative cases had cancer on histology; these were due to sampling error (the lesion was missed). A multidisciplinary team is ideal for the evaluation of breast lesions that are suspicious for malignancy as it provides one-stop shopping and same-day diagnosis and therapeutic decisions.

Aged↗
PubMed1997

The neurovascular complications of cocaine.

BACKGROUND: Cocaine use has been temporally associated with neurovascular complications, including the rupture of intracerebral aneurysms. The purpose of the current study was to determine the type of neurovascular complications associated with cocaine use in our patient population, the temporal relationship between cocaine use and their onset, and whether cocaine users with subarachnoid hemorrhage (SAH) presented with smaller aneurysms at an earlier age than a control group of noncocaine users with SAH. METHODS: Thirty-three patients who presented to the Detroit Medical Center with neurovascular sequelae associated with cocaine use were identified. All patients were chronic cocaine users who related a history of recent use confirmed by a drug screen. Cocaine users with SAH were compared to a control group of 44 patients with SAH who presented without evidence of cocaine use. RESULTS: Sixteen patients presented with SAH. Twelve patients subsequently underwent four-vessel cerebral arteriogram revealing 14 aneurysms; six patients presented with intracerebral hemorrhage (ICH) and seven patients with evidence of ischemic stroke. Eighteen (54.5%) patients noted onset of their symptoms while using cocaine, 87.9% noted onset within 6 hours of use. Delayed presentation occurred predominantly in patients who suffered ischemic strokes. The average age of patients who used cocaine and presented with SAH secondary to a ruptured intracerebral aneurysm was 32.8 years with an average aneurysm diameter of 4.9 mm versus an average age of 52.2 years with an average aneurysm diameter of approximately 11.0 mm in noncocaine users. Population differences were statistically significant at the p < 0.05 level. Mortality was 27.3% for patients who presented with neurovascular sequelae of their cocaine use, with 77.8% of deaths occurring in patients who presented with SAH. CONCLUSIONS: Chronic cocaine use appears to predispose patients who harbor incidental neurovascular anomalies to present at an earlier point in their natural history than similar non-cocaine users.

Adult↗
PubMed1997

Intestinal absorption of trace amounts of aluminium in rats studied with 26aluminium and accelerator mass spectrometry.

1. Until recently studies of intestinal aluminium absorption used pharmacological amounts of stable 27Al. 2. To examine the intestinal absorption of trace amounts of different chemical compounds of aluminium, in the present study we have employed the long half-life isotope of aluminium, 26Al, and accelerator mass spectrometry. Trace amounts of 26Al (2.7-12.1 ng) as the hydroxide, citrate, citrate plus 1 mmol/kg sodium citrate, or maltolate respectively, were administered to four groups of rats (n = 9 per group) by gavage. Blood and urine samples were collected for 5 h and the 26Al content (as a percentage of the administered dose) determined by accelerator mass spectrometry. 3. The 5 h urinary 26Al excretion amounted to 0.1 +/- 0.02, 0.7 +/- 0.2, 5.1 +/- 1.5 and 0.1 +/- 0.1% of administered dose in the four groups respectively. There was a strong positive correlation between peak plasma 26Al (r = 0.98) and urinary 26Al excretion in individual animals (P < 0.001). 4. We conclude that the fractional intestinal absorption of trace oral doses of aluminium hydroxide is at least 0.1% (compared with the previous estimate of 0.01% using large 27Al oral loads). Absorption of aluminium citrate given alone is significantly greater (0.7%) and is further increased to 5% by the accompanying sodium citrate, consistent with an enhancing effect of added citrate upon mucosal aluminium permeability. Aluminium maltolate absorption approximates that of aluminium hydroxide (0.1%).

Aluminum↗
PubMed1996

Regional and laminar differences in synaptic localization of NMDA receptor subunit NR1 splice variants in rat visual cortex and hippocampus.

Changes in N-methyl-D-aspartate (NMDA) receptor expression may represent a molecular substrate for differences in synaptic plasticity between early postnatal and adult brains (Fox and Zahs [1994] Curr. Opinion Neurobiol. 4:112-119). We have, therefore, examined the regional and laminar distribution of NR1, the essential subunit of the NMDA receptor, in two regions in which synaptic plasticity has been most thoroughly studied: primary visual cortex and hippocampus. To study NR1 expression at the light and electron microscopic levels we have used a new antiserum (NR1-C1; Sheng et al. [1994] Nature 368:144-147) directed against a differentially spliced C-terminal exon ("C1"). The most striking result was that the pattern of NR1-C1 labeling in the adult was more restricted than that of previously published NR1-specific antibodies. Specifically, NR1-C1 did not label cells in the CA3, dentate gyrus or subicular regions of the hippocampus or in layer 4 of the visual cortex. Quantitative ultrastructural analysis revealed that these differences were paralleled by differential expression of NR1-C1 at synapses. In sharp contrast to the pattern in the adult, NR1-C1 immunoreactivity was distributed more widely in the developing brain. At postnatal day 11, NR1-C1 splice variants were expressed in all layers of the visual cortex and in all regions of the hippocampus. The transient expression of NR1-C1 splice variants in layer 4 of visual cortex suggests that NR1-C1 may play a role in determining the critical period for binocular plasticity. Continued expression of NR1-C1 in upper and lower layers of the adult cortex and in CA1 of the hippocampus may provide a substrate for plasticity in corticocortical connections and Schaffer collateral synapses beyond the critical period. In addition to abundant postsynaptic staining, NR1-C1 immunoreactivity was found in a large number of axon terminals in the dorsal subiculum, but in very few terminals in visual cortex. This strongly suggests that presynaptic NMDA receptors play a major role in neuronal processing of hippocampal output through the subiculum, but play a relatively minor role in visual processing.

Alternative Splicing↗
PubMed1996

Microcircuitry of forward and feedback connections within rat visual cortex.

Visual cortex in mammals is composed of many distinct areas that are linked by reciprocal connections to form a multilevel hierarchy. Ascending information is sent via forward connections from lower to higher areas and is thought to contribute to the emergence of increasingly complex receptive field properties at higher levels. Descending signals are transmitted via feedback connections from higher to lower areas and are believed to provide information about the context in which a stimulus appears, to contribute to modulation of visual responses by attention, and to play a role in memory processes. To determine whether forward and feedback pathways in rat visual cortex constitute distinct intracortical circuits, we have studied the distribution of reciprocal corticocortical inputs to pyramidal cells and gamma-aminobutyric acid (GABA)ergic interneurons. For this purpose, we chose forward and feedback connections between primary visual cortex and the secondary extrastriate lateromedial (LM) area as a model system. Pathways were traced with the axonal marker phaseolus vulgaris-leucoagglutinin. Labeled terminals were identified in the electron microscope, and GABA immunocytochemistry was used to identify the postsynaptic dendritic shafts of GABAergic interneurons. In both pathways, inputs to pyramidal cells were directed preferentially to dendritic spines and not to shafts. In the forward pathway, 90% of labeled inputs were distributed to pyramidal cells and 10% to interneurons. This proportion was similar to that of nearby unlabeled connections in the neuropil, indicating that forward connections are not selective for pyramidal cells or interneurons. In sharp contrast, feedback connections were significantly different from the unlabeled connections and supplied almost exclusively pyramidal cells (98%). Feedback inputs to GABAergic neurons were five times weaker (2%) relative to the forward direction. These structural differences suggest that disynaptic GABAergic inhibition is much stronger in forward than in feedback pathways. Recent physiological experiments have confirmed this prediction (Shao et al. [1995] Soc. Neurosci. Abstr., 21:1274) and we, therefore, conclude that relatively small anatomical differences in the microcircuitry can have important functional consequences. It remains an open question whether generally reciprocal interareal circuits at all levels of the cortical hierarchy are organized in similar fashion.

Animals↗
PubMed1996

Trans-activation of a cell housekeeping gene promoter by the IE1 gene product of baculoviruses.

Protein IE1 is the product of a baculovirus gene, ie1, that is activated immediately upon entrance of the viral genome into the cell nucleus. This protein was previously shown to be a trans-regulator of viral genes whose products are required for initiation of the infectious cycle including viral DNA replication. To test whether the IE1 protein is also capable of trans-regulating nuclear genes of the host in vitro and in vivo, we transfected the ie1 gene of Bombyx mori nuclear polyhedrosis virus (BmNPV) into silkworm Bm5 tissue culture cells together with expression cassettes directing expression of chloramphenicol acetyl transferase or juvenile hormone esterase under the control of the cytoplasmic actin A3 gene promoter of B. mori. Cotransfection with the ie1 gene resulted in a dramatic increase in the amount of the two enzymes expressed in the transfected cells. The increased enzyme activities correlate with an increased accumulation of the corresponding mRNAs, and the latter is caused by an increase in the rate of transcription directed by the cytoplasmic actin gene promoter. The chromosomal cytoplasmic actin gene of Bm5 cells is also upregulated upon transfection of the cells with the ie1 gene. However, infection of cells with BmNPV does not cause an increase in the level of expression of the endogenous cytoplasmic actin gene. Thus, the effect of IE1 on the transcriptional properties of the cytoplasmic actin gene vary depending on whether IE1 is expressed in isolation or in the context of a viral infection. The trans-activating effects of BmNPV ie1 gene expression on the silkmoth actin promoter are also evident in Spodoptera frugiperda Sf21 and Choristoneura fumiferana Cf1 tissue culture cells. Finally, the ie1 gene of Autographa californica nuclear polyhedrosis virus can substitute for its BmNPV counterpart in all cell lines tested.

Actins↗
PubMed1996

No continuous relationship between Veterans Affairs hospital coronary artery bypass grafting surgical volume and operative mortality.

BACKGROUND: The purpose of this study was to determine whether risk-adjusted coronary artery bypass grafting mortality rates are significantly related to coronary artery bypass grafting surgical procedure volume within the Department of Veterans Affairs hospital system. METHODS: From April 1987 to September 1992, expected mortality rates were calculated for 23,986 coronary artery bypass grafting procedures performed at 44 different Veterans Affairs hospitals. RESULTS: This study found a statistically significant relationship between annual hospital coronary artery bypass grafting volume and observed mortality rates (p < 0.02). However, no statistically significant relationship between coronary artery bypass grafting volume and risk-adjusted operative mortality was found (p = 0.10). Using analysis of variance on hospital-level data, hospitals with 100 or less cases per year have higher observed to expected mortality ratios than hospitals performing more than 100 cases per year (p = 0.03). Using Poisson regression models, however, a volume threshold could not be found. CONCLUSIONS: These findings are consistent with the current Veterans Affairs policy requirements to periodically review quality at low-volume hospitals.

Analysis of Variance↗
PubMed1995

Characterization of cDNA clones for differentially expressed genes in embryos of dormant and nondormant Avena fatua L. caryopses.

The molecular regulation of seed dormancy was investigated using differential display to visualize and isolate cDNAs representing differentially expressed genes during early imbibition of dormant and nondormant Avena fatua L. embryos. Of about 3000 cDNA bands examined, 5 cDNAs hybridized with mRNAs exhibiting dormancy-associated expression patterns during the first 48 h of inhibition, while many more nondormancy-associated cDNAs were observed. Dormancy-associated clone AFD1 hybridized with a 1.5 kb mRNA barely detectable in dry dormant and nondormant embryos that became more abundant in dormant embryos after 24 h of imbibition. Clone AFD2 hybridized with two mRNAs, a 1.3 kb message constitutively expressed in dormant and nondormant embryos and a 0.9 kb message present at higher levels in dormant embryos after 3 h of imbibition. Nondormancy-associated clones AFN1, AFN2 and AFN3 hybridized with 1.5 kb, 1.7 kb and 1.1 kb mRNAs, respectively, that were more abundant in nondormant embryos during imbibition. Expression patterns of some mRNAs in dormant embryos induced to germinate by GA3 treatment were different than water controls, but were not identical to those observed in nondormant embryos. DNA sequence analysis revealed 76% sequence identity between clone AFN3 and a Citrus sinensis glutathione peroxidase-like cDNA, while significant sequence similarities with known genes were not found for other clones. Southern hybridization analyses showed that all clones represent low (1 to 4) copy number genes.

Blotting, Northern↗
PubMed1995

Identification of Eimeria bovis merozoite cDNAs using differential mRNA display.

Differences in gene expression between Eimeria bovis sporozoites and first-generation merozoites were analyzed using the technique of differential mRNA display. Approx. 5% of the sequences detected in first-generation merozoites appear to be unique relative to sporozoites. Several of the bands corresponding to merozoite-specific gene expression were isolated and cloned. Northern blot analysis revealed that the cDNA fragments DMZ-7, DMZ-8 and NMZ-6 hybridized to mRNAs expressed at > 50-fold higher levels in merozoites relative to sporozoites. A fourth cDNA fragment, NMZ-4, hybridized to a mRNA expressed at 3-fold higher levels in merozoites. Further characterization demonstrated that expression of DMZ-8 in E. bovis-infected bovine cells begins as early as 12 h after sporozoite invasion and continues throughout the entire 14 days of first-generation schizogony. Sequence analysis of each of the four merozoite cDNAs failed to identify any significant similarity to any entries in the GenBank database, suggesting that these developmentally regulated genes may be unique to coccidian parasites.

Animals↗
PubMed1995

Computational properties of self-reproducing growing automata.

Living organisms perform much better than computers at solving complex, irregular computational tasks, like search and adaptation. Key features of living organisms, identified in the paper as a basis for their success in solving complex problems, are: self-reproduction of cells, flexible framework, and modification. These key features of living organisms are abstracted into a computational model, called growing automata. Growing automata are suited for extremely large computational problems, such as search problems. Growing automata are representatives of soft machines. Soft machines can change their physical structure as opposed to hard machines which have fixed structure. An example of a soft machine is a living organism, an example of a hard machine is an electronic computer. The computational properties of soft and hard machines are analyzed and compared. An analysis of growing automata demonstrates their advantages, as well as their limitations as compared to hard machines.

Computer Simulation↗
PubMed1994

Complex interactions at a GC-rich domain regulate cell type-dependent activity of the ornithine decarboxylase promoter.

Regulation of ornithine decarboxylase (ODC) is critical to the control of cellular growth, differentiation, and carcinogenesis. A GC-rich region in the ODC promoter contains two overlapping protein binding sites that interact to regulate basal level expression in some cell types. A perfect binding motif for transcription factor Sp1 (CCCCGCCCC) is located at nucleotides -114 to -106 relative to the site of transcriptional initiation, binds strongly to purified Sp1 protein, and forms several complexes when incubated with nuclear extracts. Only one of these complexes is recognized by Sp1-specific antibody. A new protein-binding motif (GCCCCTCCCC, located at -110 to -100) partially overlaps with the Sp1 site and analyses by DNase I protection showed that a new protein ("NF-ODC1") and the Sp1-like proteins interact with the ODC promoter in a mutually exclusive manner. Mutation of the NF-ODC1 binding motif strongly enhanced ODC promoter strength in some cell types, but had little or no influence in others. The effect of mutating the Sp1 site also varied with cell type. These cell type specificities did not correlate with the levels of Sp1 and NF-ODC1 binding activities in nuclear extracts. These results show that regulation of the ODC promoter by the Sp1 family is cell type-specific and modulated by a negative effector that we have termed NF-ODC1.

Animals↗
PubMed1994

Evidence for excitatory amino acid neurotransmitters in forward and feedback corticocortical pathways within rat visual cortex.

It is a commonly accepted notion that cells which make projections between the multiple cortical areas found in the mammalian visual system are excitatory, but there is little direct evidence that this is the case. Here we demonstrate using retrograde tracing with D-[3H]aspartate that connections in the rat which project from lower to higher visual areas (i.e. forward) and those which project from higher to lower areas (i.e. feedback) may use excitatory amino acid neurotransmitters. Following injection into the primary visual cortex, clusters of retrogradely labelled cells were found in several extrastriate areas within the cytoarchitectonic subdivisions 18a ('areas' LM, AL, PX, FLX, RL, AX) and 18b ('area' MX), and in the retrosplenial cortex. In all of these areas D-[3H]aspartate-labelled cells were surrounded by diffuse label which may represent anterograde labelling of axon terminals. This suggests that both legs of reciprocal intracortical circuits have similar chemospecificity. To directly demonstrate excitatory amino acid localization in forward projections, D-[3H]aspartate was injected into extrastriate area LM. As expected, the results revealed retrogradely labelled neurons within area 17. Outside area 17, LM injections labelled neurons in AL, PX, FLX, RL, AX and MX. Taken in the context of the hierarchy of areas in rat cerebral cortex (Coogan and Burkhalter, J. Neurosci., 13, 3749-3772, 1993), these results show that D-[3H]aspartate labels: (1) forward connections from area 17 to LM, AL, PX, RL, AX and MX, (2) feedback connections from LM, AL, FLX, PX, RL, AX and MX to area 17, (3) feedback connections from AL, PX, RL, AX and MX to LM, and (4) lateral connections between FLX and LM. These findings strongly indicate that both forward and feedback connections as well as lateral connections at several different levels of the cortical hierarchy use excitatory amino acid neurotransmitters.

Animals↗
PubMed1994

Impact of mammary grafts on coronary bypass operative mortality and morbidity. Department of Veterans Affairs Cardiac Surgeons.

The internal mammary artery is frequently used as a coronary artery bypass graft conduit because of superior long-term patency. The purpose of this study was to determine if there was also an advantage to the internal mammary artery in terms of operative mortality and morbidity. The Department of Veterans Affairs Cardiac Surgery Database was reviewed for two separate time periods, April 1987 through March 1989 and October 1990 through September 1991. During these periods, 14,172 patients underwent coronary artery bypass grafting. Univariate and multivariate logistic regression analyses were used to determine preoperative variables predictive of operative mortality and morbidity, with the independent variable of use of the internal mammary artery added to previously determined indicators. The total group was analyzed in risk quartiles according to expected mortality. Univariate analysis revealed an operative mortality of 6.8% in the early period and 6.5% in the latter period for the saphenous vein groups compared with 3.7% and 3.2%, respectively, for the internal mammary artery groups (p = 0.000). Multivariate analysis revealed an odds ratio of operative death with use of the internal mammary artery graft versus use of vein grafts of 0.78 during the first period and 0.72 during the second period, reductions of 22% and 28%, respectively. There were 29% and 37% reductions in the odds of operative mortality in the highest-risk quartile group of patients using the internal mammary artery graft. The odds ratio of developing mediastinitis with one internal mammary artery graft was 1.84 (p < 0.01) in the first time period and 1.11 in the second time period (p = not significant). However, with multiple mammary bypass grafts, the odds ratios were 3.70 (p < 0.01) and 2.96 (p < 0.01) in the respective time periods. On the basis of this study, it is concluded that internal mammary artery grafts in addition to providing superior long-term patency also decreased operative mortality after adjustment for patient risk factors. Use of the mammary artery does not consistently increase operative complications with the exception of mediastinitis when both internal mammary arteries are employed.

Analysis of Variance↗
PubMed1994

The Veterans Affairs Continuous Improvement in Cardiac Surgery Study.

The Department of Veterans Affairs Cardiac Surgery Consultants Committee is responsible for reviewing the quality of cardiac surgical treatment at the 43 Veterans Affairs cardiac surgical centers where these procedures are performed. It does so by reviewing both the unadjusted and risk-adjusted operative mortality data and the incidence of perioperative complications. These data are reviewed by the committee semiannually, and the overall summary and hospital-specific data are shared with the individual cardiac surgical program directors. Paper audits and site visits are performed when indicated by increased unadjusted and risk-adjusted operative mortality. Constructive criticism is shared with the program director and medical center administration. The relative risk of death for numerous patient risk factors has been estimated, and is now used in prospective clinical decision making. During the 7-year period that risk-adjusted outcomes have been utilized, there has been an overall significant reduction in the observed-to-expected operative mortality ratio. Although many factors could have contributed to this, including continually improving surgical techniques, it is also likely that part of this improvement has occurred because of the continuous feedback of these quality improvement data to our cardiothoracic surgeons and cardiologists.

Cardiac Surgical Procedures↗
PubMed1994

Developmental regulation of an Eimeria bovis mRNA encoding refractile body-associated proteins.

Eimeria bovis antigens defined by the monoclonal antibody (mAb) 2.4 are associated with the refractile bodies of sporozoites and are found in the parasitophorous vacuole and host cell cytoplasm during schizogony. Screening of an E. bovis oocyst cDNA library with mAb 2.4 resulted in the identification of a single unique cDNA sequence (Eb-25/50). Comparison of the predicted protein sequence of Eb-25/50 revealed a high degree of identity to an Eimeria tenella refractile body protein and mAb 2.4 was found to cross-react with refractile bodies from Eimeria acervulina, demonstrating that these proteins are highly conserved among eimerian species. Measurements of Eb-25/50 mRNA showed that the multiple proteins recognized by mAb 2.4 are encoded by a single mRNA species whose kinetics of expression during sporulation and schizogony closely correlated with protein expression. Consistent with multiple Eb-25/50 proteins arising from a single polypeptide, results from a Southern analysis of E. bovis genomic DNA indicated that Eb-25/50 mRNA is derived from a single copy gene. The presence of Eb-25/50 proteins in the host cytoplasm during schizogony, the high degree of conservation of these proteins, and the apparent complex post-translational modification raises interesting questions about the biochemistry of these proteins during eimerian development.

Amino Acid Sequence↗