18 results on '"Brooks, B. R."'
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2. Interaction of DNA with Bifunctional Aldehydes.
- Author
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Brooks, B. R. and Klamerth, O. L.
- Subjects
- *
DNA , *ALDEHYDES , *ORGANIC compounds , *SUGARS , *ENZYMES , *RADIATION chemistry - Abstract
The bifunctional aldehydes glyoxal and malondialdehyde, known to be toxic products of the radiolysis of sugar and other food constituents, interact with DNA in vitro and in vivo as demonstrated by thermal denaturation profiles, chromatographic behavior, and incomplete degradation of the reaction product by deoxyribonuclease. After irradiation of DNA in diluted radioactive glucose solution followed by incubation at slightly acid pH, the radioactivity is found in the core of the enzymic digest only. Attempts to locate the binding site proved that the radiolytic compound is associated preferentially with the guanine and cytidine moiety of the DNA core. [ABSTRACT FROM AUTHOR]
- Published
- 1968
- Full Text
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3. Molecular dynamics simulations of human rhinovirus and an antiviral compound.
- Author
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Speelman B, Brooks BR, and Post CB
- Subjects
- Antiviral Agents chemistry, Biophysical Phenomena, Biophysics, Calcium chemistry, Capsid chemistry, Capsid drug effects, Humans, In Vitro Techniques, Isoxazoles chemistry, Macromolecular Substances, Models, Molecular, Protein Conformation, Protein Structure, Quaternary, Thermodynamics, Antiviral Agents pharmacology, Isoxazoles pharmacology, Rhinovirus chemistry, Rhinovirus drug effects
- Abstract
The human rhinovirus 14 (HRV14) protomer, with or without the antiviral compound WIN 52084s, was simulated using molecular dynamics and rotational symmetry boundary conditions to model the effect of the entire icosahedral capsid. The protein asymmetrical unit, comprising four capsid proteins (VP1, VP2, VP3, and VP4) and two calcium ions, was solvated both on the exterior and the interior to fill the inside of the capsid. The stability of the simulations of this large system (~800 residues and 6,650 water molecules) is comparable to more conventional globular protein simulations. The influence of the antiviral compound on compressibility and positional fluctuations is reported. The compressibility, estimated from the density fluctuations in the region of the binding pocket, was found to be greater with WIN 52084s bound than without the drug, substantiating previous computations on reduced viral systems. An increase in compressibility correlates with an entropically more favorable system. In contrast to the increase in density fluctuations and compressibility, the positional fluctuations decreased dramatically for the external loops of VP1 and the N-terminus of VP3 when WIN 52084s is bound. Most of these VP1 and VP3 loops are found near the fivefold axis, a region whose mobility was not considered in reduced systems, but can be observed with this simulation of the full viral protomer. Altered loop flexibility is consistent with changes in proteolytic sensitivity observed experimentally. Moreover, decreased flexibility in these intraprotomeric loops is noteworthy since the externalization of VP4, part of VP1, and RNA during the uncoating process is thought to involve areas near the fivefold axis. Both the decrease in positional fluctuations at the fivefold axis and the increase in compressibility near the WIN pocket are discussed in relationship to the antiviral activity of stabilizing the virus against uncoating.
- Published
- 2001
- Full Text
- View/download PDF
4. Synthesis of virus-specific high-mobility DNA after temperature upshift of SC-1 cells chronically infected with moloney murine leukemia virus mutant ts1.
- Author
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Szurek PF and Brooks BR
- Subjects
- Animals, Cell Line, DNA, Viral chemistry, Electrophoresis, Agar Gel, Fibroblasts virology, In Situ Hybridization, Mice, Moloney murine leukemia virus physiology, Mutation, Paralysis, Retroviridae Infections virology, Spinal Cord metabolism, Spinal Cord pathology, Spinal Cord virology, Temperature, Time Factors, Tumor Virus Infections virology, DNA, Viral biosynthesis, Moloney murine leukemia virus genetics
- Abstract
Premature termination products of reverse transcription that consist physically of viral minus-sense single-stranded DNA that is shorter than one long terminal repeat and partial DNA duplexes are dramatically increased in the central nervous system (CNS) of FVB/N mice that are infected by ts1, a temperature-sensitive mutant of Moloney murine leukemia virus. Due to their migration in agarose gels, these incomplete physical forms of DNA have been designated high-mobility (HM) DNA. In non-CNS tissues, the level of HM DNA is either low or not detectable. In order to determine the conditions that are necessary for the synthesis of HM DNA in vivo, we have characterized the physical forms of HM DNA that were synthesized in vitro in chronically infected SC-1 cells after temperature upshift. At the permissive temperature of 34 degrees C, the chronically infected SC-1 cells did not synthesize HM DNA. After temperature upshift of the cultured cells from 34 to 37 degrees C, the chronically infected SC-1 cells developed extremely high levels of HM DNA. Following temperature downshift of the cultured cells from 37 to 34 degrees C, a decrease in the level of HM DNA and an increase in the level of unintegrated linear proviral DNA occurred simultaneously. These results suggested that the accumulation of HM DNA both in vitro and in vivo may be the result of superinfection.
- Published
- 2000
- Full Text
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5. ts1-Induced spongiform encephalomyelopathy: physical forms of high-mobility DNA in spinal cord tissues of paralyzed mice are products of premature termination of reverse transcription.
- Author
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Szurek PF and Brooks BR
- Subjects
- Animals, Cell Line, Central Nervous System Diseases pathology, DNA analysis, DNA Probes, DNA, Antisense, DNA, Viral chemistry, Mice, Mutation, Paralysis pathology, Paralysis virology, Repetitive Sequences, Nucleic Acid, Retroviridae Infections pathology, Tumor Virus Infections pathology, Central Nervous System Diseases virology, DNA, Viral analysis, Moloney murine leukemia virus genetics, Retroviridae Infections virology, Transcription, Genetic, Tumor Virus Infections virology
- Abstract
ts1 is a temperature-sensitive mutant of Moloney murine leukemia virus that causes hind-limb paralysis in mice. In tissues of the central nervous systems of paralyzed moribund FVB/N mice, a major component of the unintegrated viral DNA of ts1 consists of highly mobile physical forms of viral-specific DNA (HM DNA). Previous studies with ecotropic virus-specific polarity probes showed that the gp70-coding region of the env gene in the HM DNA was minus-sense single-stranded DNA. The physical forms of the HM DNA have now been characterized in more detail with additional ecotropic virus-specific probes that hybridized to the p15E-coding region of the env gene and two locations within the U3 region of the long terminal repeat. Two major classes of HM DNA were found: class I molecules consist of short minus-sense single-stranded DNA; class II molecules are partial DNA duplexes that are longer than the class I molecules. The two classes of HM DNA molecules are intermediate products of reverse transcription of the viral RNA of ts1. Since tissues that are infected with cytopathic retroviruses may contain high levels of unintegrated viral DNA, the HM DNA may have a role in inducing neurodegeneration in the central nervous systems of mice that are infected with ts1.
- Published
- 1996
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6. Hydrated myoglobin's anharmonic fluctuations are not primarily due to dihedral transitions.
- Author
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Steinbach PJ and Brooks BR
- Subjects
- Biophysical Phenomena, Biophysics, Computer Simulation, Motion, Temperature, Water, Myoglobin chemistry
- Abstract
To characterize the functionally important anharmonic motions of proteins, simulations of carboxymyoglobin (MbCO) dynamics have been performed during which dihedral transitions were prohibited. Comparison of torsionally restrained and unrestrained protein dynamics simulated at three levels of hydration and at temperatures ranging from 100 to 400 K suggests that hydration "catalyzes" protein mobility by facilitating collective anharmonic motions that do not require dihedral transitions. When dihedral transitions were prohibited, dehydrated MbCO, to a good approximation, exhibited only harmonic fluctuations, whereas hydrated MbCO exhibited both harmonic and anharmonic motions. The fluctuation of helix centers of mass also remained highly anharmonic in the torsionally restrained hydrated system. Atomic mean-square fluctuation at 300 K was reduced upon prohibition of dihedral transitions by only 28% and 10% for MbCO hydrated by 350 and 3830 water molecules, respectively.
- Published
- 1996
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7. Development of physical forms of unintegrated retroviral DNA in mouse spinal cord tissue during ts1-induced spongiform encephalomyelopathy: elevated levels of a novel single-stranded form in paralyzed mice.
- Author
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Szurek PF and Brooks BR
- Subjects
- Animals, Base Sequence, Brain virology, Cell Line, Chromosomes, DNA, Viral genetics, Kinetics, Mice, Molecular Sequence Data, Moloney murine leukemia virus genetics, Nucleic Acid Hybridization, Recombination, Genetic, Virus Integration, DNA, Single-Stranded metabolism, DNA, Viral metabolism, Moloney murine leukemia virus physiology, Paralysis virology, Prion Diseases virology, Spinal Cord virology
- Abstract
ts1 is a murine leukemia virus that causes rapidly evolving hindlimb paralysis in susceptible strains of mice. Following perinatal infection, three physical forms of unintegrated viral DNA were detected in the spinal cord by Southern blot hybridization. Linear and supercoiled closed-circle viral double-stranded DNAs were detected in both the central nervous system and non-central nervous system tissues. An elevated level of a novel minus-sense single-stranded form of viral DNA, which had a very high mobility in agarose gels, was correlated with the onset of symptoms of paralysis. As the severity of paralysis progressed, the level of this single-stranded form increased rapidly, with the highest level in the spinal cords of moribund mice. Since the virulence of a number of cytopathic retroviruses has been associated with the presence of increased amounts of unintegrated viral DNA in the tissues of the infected hosts, this novel form of highly mobile unintegrated single-stranded DNA may have a role in the neuropathogenesis of ts1.
- Published
- 1995
- Full Text
- View/download PDF
8. Protein hydration elucidated by molecular dynamics simulation.
- Author
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Steinbach PJ and Brooks BR
- Subjects
- Computer Simulation, Hydrogen Bonding, Models, Molecular, Software, Thermodynamics, Water, X-Ray Diffraction, Myoglobin chemistry, Protein Conformation, Proteins chemistry
- Abstract
Molecular dynamics (MD) simulation covering a wide range of hydration indicate that myoglobin is fully hydrated by 350 water molecules, in agreement with experiment. These waters, originally placed uniformly about the protein, form clusters that hydrate every charged group throughout the entire simulation. Some atoms in charged groups are hydrated by two water layers while 37% of the protein surface remains uncovered. The locations of the 350 waters are consistent with those of crystallographic waters resolved by x-ray and neutron diffraction. Hydration by 350 waters at 300 K stabilizes the conformation of carboxymyoglobin measured by x-ray diffraction throughout the entire protein, halves the rate of torsional transitions, and promotes alternative conformations for surface atoms. The glass transition observed experimentally in hydrated myoglobin near 220 K is also seen in the simulations and correlates with an increase in the number of dihedral angles undergoing transitions. The anharmonic protein motion above 220 K is enhanced by protein hydration.
- Published
- 1993
- Full Text
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9. Correlation of specific virus-astrocyte interactions and cytopathic effects induced by ts1, a neurovirulent mutant of Moloney murine leukemia virus.
- Author
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Shikova E, Lin YC, Saha K, Brooks BR, and Wong PK
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- Animals, Astrocytes ultrastructure, Cell Compartmentation, Cells, Cultured, Cytopathogenic Effect, Viral, Diencephalon cytology, Endoplasmic Reticulum metabolism, Endothelium, Vascular cytology, Endothelium, Vascular microbiology, Golgi Apparatus metabolism, Mice, Mice, Inbred Strains, Moloney murine leukemia virus genetics, Mutation, Protein Precursors blood, Protein Processing, Post-Translational, Viral Envelope Proteins blood, Virulence, Astrocytes microbiology, Moloney murine leukemia virus pathogenicity
- Abstract
ts1 is a highly neuropathogenic and lymphocytopathic mutant of Moloney murine leukemia virus TB (MoMuLV-TB). We previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-->Ile, in precursor envelope protein gPr80env. This Val-25-->Ile substitution apparently renders gPr80env inefficient for transport from the endoplasmic reticulum to the Golgi apparatus. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to the accumulation of gPr80env in the endoplasmic reticulum. Since endothelial and glial cells are targets of ts1 infection in the central nervous system, we established primary endothelial and astrocyte cultures to investigate the mechanism of cell killing caused by ts1. A continuous cell line, TB, was used as a control. Our results showed that both ts1 and MoMuLV-TB replicated and induced a cytopathic effect in astrocyte cultures, albeit to different degrees; ts1 appeared to be more lethal than MoMuLV-TB. On the other hand, ts1 and MoMuLV-TB infections of endothelial or TB cells were not cytopathic. The cytopathic effect in infected astrocytes correlated with the inefficiency of gPr80env transport and the intracellular accumulation of gPr80env as well as aberrant virus particles.
- Published
- 1993
- Full Text
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10. Metabolism-based transformation of myoglobin to an oxidase by BrCCl3 and molecular modeling of the oxidase form.
- Author
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Osawa Y, Darbyshire JF, Steinbach PJ, and Brooks BR
- Subjects
- Animals, Dihydrolipoamide Dehydrogenase metabolism, Heme chemistry, In Vitro Techniques, Metmyoglobin metabolism, Models, Molecular, Myoglobin chemistry, Myoglobin drug effects, NAD metabolism, Oxidation-Reduction, Oxygen Consumption, Protein Structure, Tertiary, Structure-Activity Relationship, Whales, Bromotrichloromethane pharmacology, Myoglobin metabolism, Oxidoreductases metabolism
- Abstract
The stoichiometric reductive debromination of BrCCl3 to a trichloromethyl radical by myoglobin caused the prosthetic heme to become covalently cross-linked to the protein moiety and transformed myoglobin from an oxygen storage protein to an oxidase. This was shown in experiments in which oxygen consumption was measured during redox cycling of the altered myoglobin in the presence of ascorbate or an enzymatic reducing system containing diaphorase and NADH. Redox cycling eventually led to loss of the protein-bound heme adduct and oxidase activity of myoglobin. We have used molecular modeling and the known structure of the protein-bound heme adduct to identify probable mechanisms for transformation of myoglobin to an oxidase. Based on these modeling studies, the most likely structure of the experimentally observed adduct involves ligation to the heme iron of the epsilon-nitrogen atom of histidine 97 and/or that of histidine 64. The model structures revealed access of solvent to the heme active site, which could facilitate oxygen reduction. The transformation of myoglobins and perhaps other hemoproteins to oxidases may have toxicological importance in causing the tissue damage resulting from exposure to various xenobiotics and endogenous chemicals as well as explaining how hemoproteins are inactivated during catalysis.
- Published
- 1993
11. Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB.
- Author
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Wong PK, Szurek PF, Floyd E, Saha K, and Brooks BR
- Subjects
- Animals, Atrophy, B-Lymphocytes pathology, Base Sequence, Cell Death, Cell Line, Chimera, Cloning, Molecular, Corticosterone blood, DNA, Viral genetics, Genome, Viral, Mice, Molecular Sequence Data, Moloney murine leukemia virus immunology, Moloney murine leukemia virus pathogenicity, Mutation, Paralysis blood, Paralysis pathology, Plasmids, T-Lymphocytes pathology, Virulence genetics, B-Lymphocytes microbiology, Moloney murine leukemia virus genetics, Paralysis microbiology, Repetitive Sequences, Nucleic Acid, T-Lymphocytes microbiology, Thymus Gland pathology
- Abstract
The ts1 mutant of Moloney murine leukemia virus TB causes degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. To investigate the pathogenesis of the thymic atrophy caused by ts1, we constructed a chimeric virus, ts1-Cas(NS), in which a major portion of the U3 region of the long terminal repeat of ts1, a T-lymphotropic and neurovirulent murine leukemia virus, was replaced by the corresponding U3 region of Cas-Br-E, a B-lymphotropic and neurovirulent murine leukemia virus. In FVB/N mice, ts1-Cas(NS) induced paralytic and wasting disease with incidence, severity, and latency similar to that induced by ts1, but it failed to cause thymic atrophy as severe as that observed in ts1-infected mice. Furthermore, thymocytes cultured from ts1-Cas(NS)-infected mice died at a much slower rate than those of ts1-infected mice. The U3 substitution in ts1-Cas(NS) specifically diminished the ability of the virus to replicate in the thymus, whereas viral replication in the spinal cord was not significantly affected; thus, neurovirulence was not changed. The correlation of reduced thymic atrophy with decreased thymic viral titers and the decreased ability of ts1-Cas(NS) to cause thymocyte death in mice suggest strongly that the marked thymic atrophy in ts1-infected mice is not an indirect effect occurring secondary to neurodegenerative and wasting disease but is a direct cytopathic effect of high-level viral replication in the thymus.
- Published
- 1991
- Full Text
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12. Solution conformations of the B-loop fragments of human transforming growth factor alpha and epidermal growth factor by 1H nuclear magnetic resonance and restrained molecular dynamics.
- Author
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Han KH, Syi JL, Brooks BR, and Ferretti JA
- Subjects
- Computer Simulation, Humans, Hydrogen, Magnetic Resonance Spectroscopy methods, Models, Molecular, Protein Conformation, Solutions, Thermodynamics, Epidermal Growth Factor, Transforming Growth Factors
- Abstract
A restrained molecular dynamics simulation approach that explicitly includes the effect of the surrounding solvent molecules is applied to the NMR determination of the conformations of the B-loop fragments of human transforming growth factor alpha and epidermal growth factor. Backbone interproton distance restraints are obtained by using two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY). The simulations are carried out both in "vacuum" and in "water." The results are discussed in terms of the energetics, agreement with the NMR distances, and the flexibility of the peptides.
- Published
- 1990
- Full Text
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13. Absorption mode two-dimensional NOE spectroscopy of exchangeable protons in oligonucleotides.
- Author
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Sklenár V, Brooks BR, Zon G, and Bax A
- Subjects
- Amines, Chemical Phenomena, Chemistry, Physical, Imines, Magnetic Resonance Spectroscopy, Protons, Water, Oligodeoxyribonucleotides
- Abstract
A new NMR method is described for the generation of absorption mode two-dimensional NOE spectra of oligonucleotides in H2O solution. The method yields spectra that are free of baseline distortions with excellent suppression of the intense H2O resonance. The method is demonstrated for a sample of the dodecamer d(CGCGAATTCGCG)2. All exchangeable base protons are identified and a number of new types of NOE connectivities are observed.
- Published
- 1987
- Full Text
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14. Demonstration of thyrotropin-releasing hormone immunoreactivity in neurons of the mouse spinal dorsal horn.
- Author
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Coffield JA, Miletic V, Zimmermann E, Hoffert MJ, and Brooks BR
- Subjects
- Animals, Immunoenzyme Techniques, Mice, Neurons immunology, Neurons metabolism, Spinal Cord immunology, Thyrotropin-Releasing Hormone immunology, Spinal Cord metabolism, Thyrotropin-Releasing Hormone metabolism
- Abstract
Thyrotropin-releasing hormone-like immunoreactivity was demonstrated in neurons within the superficial laminae (I, II, III) of the mouse spinal dorsal horn by light-microscopic peroxidase immunocytochemistry. The immunoreactivity was distributed in a narrow dorsoventral band that enclosed the substantia gelatinosa (lamina II), with a higher concentration along the lamina II/III border. At present, the functional significance of these neurons is unknown. Their existence within the substantia gelatinosa suggests a role in sensory information processing.
- Published
- 1986
15. Murine neurotropic retrovirus spongiform polioencephalomyelopathy: acceleration of disease by virus inoculum concentration.
- Author
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Brooks BR, Swarz JR, Narayan O, and Johnson RT
- Subjects
- Animals, Brain Stem microbiology, Mice, Mice, Inbred BALB C, Spinal Cord microbiology, Time Factors, Central Nervous System Diseases microbiology, Retroviridae growth & development, Virus Diseases microbiology
- Abstract
A 10-fold reduction in the incubation period of murine neurotropic retrovirus spongiform polioencephalomyelopathy was effected by a 1,000-fold concentration of the cloned virus inoculum.
- Published
- 1979
- Full Text
- View/download PDF
16. Theoretically determined three-dimensional structure for the repeating tetrapeptide unit of the circumsporozoite coat protein of the malaria parasite Plasmodium falciparum.
- Author
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Brooks BR, Pastor RW, and Carson FW
- Subjects
- Animals, Chemical Phenomena, Chemistry, Physical, Computer Simulation, Models, Molecular, Protein Conformation, Antigens, Protozoan, Antigens, Surface, Plasmodium falciparum immunology, Protozoan Proteins
- Abstract
A model for the three-dimensional structure of the repeating Asn-Pro-Asn-Ala tetrapeptide of the immunodominant circumsporozoite protein of Plasmodium falciparum has been developed. A trial structure in the form of a type I beta turn with asparagine side chains hydrogen-bonded to the backbone peptide linkages was used as a starting point. A repeating oligomer of this trial structure was modeled using energy minimization and molecular dynamics computer simulations in conjunction with image boundary conditions. The most stable structure generated is a right-handed 12(38) helix, which is unlike any previously identified protein secondary structure. The helix has 12 residues per turn, corresponding to an angle of twist of 120 degrees per tetrapeptide unit, and a pitch of 4.95 A, corresponding to a rise of 1.65 A per tetrapeptide unit. It is highly stabilized by extensive hydrogen bonding, with each tetrapeptide unit acting as an acceptor for five hydrogen bonds and as a donor for five hydrogen bonds to residues in adjacent turns as well as having four weak internal hydrogen bonds. A number of nearly isoenergetic variations on the most stable structure that still retained the basic 12(38) helical motif were also discovered. The implications of these structures for vaccine development are discussed.
- Published
- 1987
- Full Text
- View/download PDF
17. Acute posterior multifocal placoid pigment epitheliopathy associated with cerebral vasculitis.
- Author
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Weinstein JM, Bresnick GH, Bell CL, Roschmann RA, Brooks BR, and Strother CM
- Subjects
- Adult, Humans, Male, Retinal Diseases diagnosis, Vasculitis diagnosis, Brain blood supply, Pigment Epithelium of Eye, Retinal Diseases complications, Vasculitis complications
- Abstract
Acute multifocal posterior placoid pigment epitheliopathy (APMPPE) is an unusual self-limited retinal disorder that has been associated with various systemic complications. To our knowledge, three prior cases associated with cerebral vasculitis have been described. This article describes a patient with APMPPE and angiographically documented cerebral vasculitis who was notable because of (a) the presence of two different cerebral ischemic events, occurring 1 month apart, and (b) the long latency (3 months) between the onset of ocular symptoms and the second cerebral ischemic event. Recognition of the association between APMPPE and cerebral vasculitis may permit early treatment of CNS involvement and prevention of morbidity.
- Published
- 1988
18. Aggression.
- Author
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Brooks BR
- Subjects
- Humans, Nurse-Patient Relations, Aggression, Psychiatric Nursing
- Published
- 1967
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