The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

OBJECTIVE\nTo develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE).\n\n\nMETHODS\nAn international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests.\n\n\nRESULTS\nCase definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed.\n\n\nCONCLUSION\nThe American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

http://diabetestype2.ca/diary/research/glutathione/immunocal/Glutathione-metabolism-in-brain.pdf

Metabolism and functions of glutathione in brain.

The cytology of the postmitotic migratory granule cell and its relationship to Bergmann glial processes was examined with Golgi staining and electron microscopy in the three cardinal planes in the developing cerebellar cortex of Macacus rhesus at various late fetal and early postnatal ages. After final mitosis the granule cell body transforms from a nearly round shape in the superficial zone of the external granular layer to a horizontal bipolar form with elongated processes oriented longitudinally to the folium, at the outer border of the molecular layer. Another descending process develops, and the cell soma becomes a pyramid flattened in the plane longitudinal to the folium. The nucleus moves into the descending process and the cell soma assumes a vertically oriented spindle shape while migrating among previously formed parallel fibers deeper in the molecular layer, and finally attains a round shape again when it lies deep to the Purkinje cell layer. During these transformations, the cell cytoplasm becomes more voluminous and contains a prominent Golgi apparatus, numerous free ribosomes, mitochondria, multivesicular and dense bodies, and fascicles of microtubules Longitudinally oriented microtubules concentrated in the vertical leading process disappear by the time the cell soma enters the granular layer. The slender trailing process loss most of its cytoplasmic organelles, acquires microtubules and together with the horizontal processes forms the characteristic T-shaped axon. The axon forms synapses with Purkinje and stellate cell dendrites at a time when other granule cells are still migrating among them.

During the entire course of their migration across the molecular layer, granule cells are directly apposed to vertically oriented Bergmann fibers belonging to the Golgi epithelial cells. The sequence of developmental stages indicates that Golgi epithelial cells are a type of protoplasmic astrocyte. The Bergmann fibers were present at all stages examined, and their constant apposition to granule cells suggests a role in the lartter's migration. Numerous electronluscent beady enlargements are seen along the fiber except at sites were the surface is in contact with migrating cells; probably these enlargements change position as the granule cells pass along the Bergmann fiber. Lamellate expansions also project from the main shaft of the glial fiber and envelop the synaptic sites on spines of Purkinje cell dendrites. These expansions seem more durable, and the young neuron appears to avoid collision with them by sprialling around the glial shaft during its descent to the granular layer. The neuron-glia relationship apparently provides the necessary conditions for the migration of the young granule cell. Especially at late developmental stages when the molecular layer is more than 250 μ wide and is densely packed with highly oriented cell processes that have already established synaptic connections.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cne.901410303

Neuron‐glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electonmicroscopic study in Macacus rhesus

Neuronal migration, with special reference to developing human brain: a review.

The electrostatic adsorption of poly-L-lysine molecules onto a vapor-deposited gold film modified with a carboxylic acid-terminated alkanethiol monolayer is monitored with the spectroscopic techniques of polarization-modulation Fourier transform infrared (PM-FTIR) spectroscopy and surface plasmon resonance (SPR). The PM-ITIR spectrum of a monolayer of poly-L-lysine (PL) adsorbed onto a self-assembled monolayer of 11-mercaptoundecanoic acid (MUA) indicates that the lysine residues and the MUA carboxylic acid moieties form ammonium-carboxylate ion pairs which electrostatically bind the polypeptide to the surface. The PL molecules can be desorbed from the surface by rinsing with a buffer solution at a pH that destroys the ion pairing (pH 12). Measurements of the shift in the SPR angle upon adsorption were used to determine the thicknesses of the adsorbed monolayers; the MUA and PL monolayers were found to be 17.0 and 10.5 A thick, respectively. These thickness results suggest that the poly-L-lysine monolayer adsorbs onto the packed MUA surface in an extended conformation with the PL backbone lying parallel to the surface. Subsequent exposure ofthe PL monolayer to a solution ofiron phthalocyanine tetracarboxylic acid (FePc) resulted in the adsorption of a third layer onto the surface. The ability of the adsorbed PL molecules to interact with FePc indicates the presence of free lysine residues available for interaction with molecules other than the MUA monolayer.

Characterization of poly-L-lysine adsorption onto alkanethiol-modified gold surfaces with polarization-modulation Fourier transform infrared spectroscopy and surface plasmon resonance measurements

The glutathione S-transferases (GSTs) constitute a family of cytosolic isoenzymes and a structurally unrelated microsomal enzyme that is involved in the detoxication of electrophilic xenobiotics. These enzymes also participate in the intracellular binding and transport of a broad range of lipophilic compounds including bilirubin, and hormones such as the glucocorticoids and thyroid hormones. The present investigation demonstrates that GSTs are present in neurons of the brainstem, forebrain, and cerebellum. An isoenzyme-specific distribution of GSTs was found in cytoplasm, nuclei, and nucleoli. The regional and cellular distribution of cytosolic GSTs in the brain was studied by immunohistochemistry, spectrophotometric enzyme assay, and reverse-phase HPLC. Polyclonal antibody against microsomal GST was strongly reactive with Purkinje cells throughout the cerebellar cortex, and with neurons in the brainstem and hippocampus. Nuclei of Purkinje cells and of neurons in the brainstem, hippocampus, and cerebral cortex were immunopositive for alpha-class GST 1-1 (YaYa), whereas alpha-class GST 2-2 (YcYc) antibody was consistently immunoreactive with the nucleolus, but not with the nucleus or soma. All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels. Reverse-phase HPLC indicated that there were also substantial regional differences in the pattern of alpha-, mu-, and pi-class GST subunit expression. For example, the thalamus/hypothalamus had the highest GST activity and greatest concentration of total GST protein and mu-class GST subunit 6 (Yb3), whereas the brainstem had the greatest concentration of pi-class GST subunit (Yp). This regional variation in GST expression may be reflective of regional differences in cell populations. In cerebellar cortex, the concentration of mu-class GST subunit 4 (Yb2) was greatest in the flocculus and lowest in the vermis. This is of clinical interest because the pattern of expression of mu-class GST subunit 4 (Yb2) in the cerebellum coincides with the known regional susceptibility of this structure to degeneration after exposure to toxic or metabolic insults. The vermis is most susceptible to these insults, whereas the lateral lobes and flocculus are most resistant.(ABSTRACT TRUNCATED AT 400 WORDS)

https://www.jneurosci.org/content/jneuro/13/5/2013.full.pdf

Glutathione S-transferase isoenzymes in rat brain neurons and glia

Autoimmune basis for visual paraneoplastic syndrome in patients with small-cell lung carcinoma

Monolayers of the polypeptide poly(L-lysine) (PL) are used to control the specific adsorption of proteins onto gold surfaces. A PL monolayer modified with biotin is electrostatically adsorbed onto a vapor-deposited gold film that has been coated with a self-assembled monolayer of the alkanethiol 11-mercaptoundecanoic acid (MUA). The immobilized biotin moieties act as specific adsorption sites for the protein avidin. Adsorption of the biopolymers onto the gold surface is monitored with a combination of surface plasmon resonance (SPR) and fluorescence measurements. By varying the percent biotinylation of the lysine residues on the PL prior to deposition, the surface coverage of avidin can be controlled to create either full or partial monolayers. The thickness of a full monolayer of avidin is 41 A, as determined by the SPR measurements. At high surface coverages of avidin, an excess of biotin sites is required to overcome steric hindrance. The PL monolayer and any adsorbed avidin can be easily rinsed from the surface with a low or high pH solution. This removal allows for quantitation of the adsorbed molecules by fluorescence measurements in solution rather than on the gold surface. In this manner, fluorescein-labeled PL and avidin are used to determine absolute surface coverages of 4 x 10 14 lysine residues cm -2 for the PL monolayer and 3 x 10 12 avidin molecules cm -2 for the full avidin monolayer. SPR imaging experiments are employed to verify that UV photopatterning of the MUA/PL bilayers can be used to spatially direct the adsorption of avidin onto the gold surface. The polylysine attachment methodology will be beneficial in the fabrication of adsorption biosensors.

Control of the Specific Adsorption of Proteins onto Gold Surfaces with Poly(L-lysine) Monolayers

Clinical, magnetic resonance imaging (MRI), and serologic studies were performed on 11 patients with diffuse central nervous system (CNS) systemic lupus erythematosus and 8 patients with focal CNS lupus. MRI of patients with diffuse clinical disease showed symmetrically distributed areas of increased signal intensity in the subcortical white matter; these resolved after treatment with high-dose methylprednisolone. These patients' sera contained elevated levels of antineurofilament antibodies. Patients with focal CNS lupus had areas of increased signal intensity and atrophic changes in regions corresponding to the major cerebral vessels. These MRI abnormalities did not improve after treatment with high-dose steroids. The sera of patients with focal CNS lupus had elevated levels of cardiolipin and lupus anticoagulant but normal levels of antineurofilament antibody. Our findings suggest that results of a combined clinical, MRI, and serologic evaluation of patients with CNS lupus may predict the response of patients to high-dose steroid therapy.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780340408

Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers

Steven Kornguth

Papers

Characterization of poly-L-lysine adsorption onto alkanethiol-modified gold surfaces with polarization-modulation Fourier transform infrared spectroscopy and surface plasmon resonance measurements

Glutathione S-transferase isoenzymes in rat brain neurons and glia

Autoimmune basis for visual paraneoplastic syndrome in patients with small-cell lung carcinoma

Control of the Specific Adsorption of Proteins onto Gold Surfaces with Poly(L-lysine) Monolayers

Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers