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S P Markey

Publications and source records attributed to S P Markey.

At least 19 recordsLinked to original sources
PubMed1996

Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated.

Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immunodeficiency syndrome (murine AIDS) and an encephalopathy characterized by impaired spatial learning and memory. Because platelet-activating factor (PAF) has been implicated in the pathogenesis of HIV-associated dementia complex, brain PAF levels were measured in LP-BM5 MuLV-infected mice. PAF levels in cerebral cortex and hippocampus were significantly increased at 6 and 12 weeks after LP-BM5 MuLV inoculation, whereas significant increases in striatal and cerebellar PAF levels were observed only at 12 weeks after inoculation. Administration of the NMDA antagonist MK-801 significantly reduced the increased PAF levels in the cerebral cortex and hippocampus of LP-BM5 MuLV-infected mice. These results indicate that the LP-BM5 MuLV-induced increases in brain PAF levels are the results of NMDA receptor activation and are consistent with the hypothesis that elevated CNS PAF levels contribute to the behavioral deficits observed in LP-BM5 MuLV-infected mice.

AIDS Dementia Complex↗
PubMed1996

Platelet-activating factor in brain regions after transient ischemia in gerbils.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) has been reported to be an active mediator in ischemic brain damage on the basis of indirect pharmacological data from PAF antagonists. The direct measurement of PAF in neuronal tissues has not been reported previously in analogous animal models. We have examined regional brain PAF concentration changes during the reperfusion period after ischemia in gerbils to obtain direct evidence for the involvement of PAF with ischemic brain damage and reported gas chromatography/mass spectrometry (GC/MS) methods of PAF quantitative analysis in brain tissues. METHODS: After transient (10 minutes) ischemia followed by controlled periods (0 to 96 hours) of reperfusion and recovery, regional PAF concentrations were determined in gerbil brain tissue. Quantitative analysis of PAF in brain regions is performed using an electron-capture negative chemical ionization GC/MS method, modified for brain tissue. RESULTS: The level of PAF was increased significantly and maximally in hippocampus (211%), cortex (168%), and thalamus (169%) after 1 hour of reperfusion. In contrast, there were no significant changes of PAF in any brain region from 6 hours to 96 hours after reperfusion. CONCLUSIONS: PAF is increased in gerbil brain in response to ischemia at early stages of reperfusion. PAF increases could contribute to the onset and progress of ischemic neuropathology.

Animals↗
PubMed1995

Purification and identification of pituitary cytotropic factor.

It has been shown that the pituitary contains a cytotropic factor (CTF) that stimulates the secretion of catecholamines by dopaminergic neurons of the hypothalamus. In the present study, CTF was purified from rat pituitaries and found by means of mass spectrometric analysis to be adenosine. This finding was corroborated by the observations that CTF behaves identically to adenosine when subjected to liquid chromatography, is inactivated and converted to inosine by adenosine deaminase, and is qualitatively and quantitatively indistinguishable from adenosine in its biological activity. It is concluded that pituitary adenosine is a trophic factor for hypothalamic dopaminergic neurons.

Adenosine↗
PubMed1995

Pentafluorobenzylation method for quantification of acidic tryptophan metabolites using electron capture negative ion mass spectrometry.

An improved pentafluorobenzylation method was developed for derivatization of L-tryptophan and its acidic metabolites (L-kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, 3-hydroxyanthranilic acid, picolinic acid, quinolinic acid) present at trace levels in aqueous samples. This method employs lyophilization of aqueous samples in the presence of excess tetrabutylammonium hydrogen sulfate, followed by base-catalyzed anhydrous pentafluorobenzylation. A comparison with other published methods shows the advantage of this modification for the derivatization of kynurenine metabolites. The derivatives were analyzed by gas chromatography/electron capture negative ion mass spectrometry (GC/ECNI-MS) or liquid chromatography/particle beam/ECNI-MS (LC/ECNI-MS). The detection limits for injected standards are in the femtogram range by GC/ECNI-MS and in the low picogram range by LC/ECNI-MS. GC/ECNIMS is 3.6 (xanthurenic acid) to 66 (quinolinic acid) times more sensitive than LC/ECNI-MS. The simultaneous determination of two neuroactive metabolites, quinolinic and kynurenic acids, in culture medium is presented. The minimum measurable concentrations of these metabolites in 100 microL of culture medium are 0.11 nM for quinolinic acid and 0.21 nM for kynurenic acid.

Fluorobenzenes↗
PubMed1995

Metabolism of L-tryptophan to kynurenate and quinolinate in the central nervous system: effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate.

The metabolism of L-tryptophan to the neuroactive kynurenine pathway metabolites, L-kynurenine, kynurenate and quinolinate, and the effects of two inhibitors of quinolinate synthesis (6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate) were investigated by mass spectrometric assays in cultured cells and in vivo. Cell lines obtained from astrocytoma, neuroblastoma, macrophage/monocytes, lung, and liver metabolized L-[13C6]-tryptophan to L-[13C6]kynurenine and [13C6]kynurenate, particularly after indoleamine-2,3-dioxygenase induction by interferon-gamma. Kynurenine aminotransferase activity was measurable in all cell types examined but was unaffected by interferon-gamma. These results suggest that many cell types can be sources of kynurenate following immune activation. In vivo synthesis of L-[13C6]kynurenine and [13C6]kynurenate from L-[13C6]tryptophan was studied in the CSF of macaques infected with poliovirus, as a model of inflammatory neurologic disease. The effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate on the synthesis of kynurenate were different. 6-Chlorotryptophan attenuated formation of L-[13C6]kynurenine and [13C6]kynurenate and was converted to 4-chlorokynurenine and 7-chlorokynurenate. It may be an effective prodrug for the delivery of 7-chlorokynurenate, which is a potent antagonist of NMDA receptors. In contrast, 4-chloro-3-hydroxyanthranilate did not reduce accumulation of L-[13C6]kynurenine and [13C6]kynurenate. 6-Chlorotryptophan and 4-chloro-3-hydroxyanthranilate are useful tools to manipulate concentrations of quinolinate and kynurenate in the animal models of neurologic disease to evaluate physiological roles of these neuroactive metabolites.

3-Hydroxyanthranilic Acid↗
PubMed1994

6-Chloro-D,L-tryptophan, 4-chloro-3-hydroxyanthranilate and dexamethasone attenuate quinolinic acid accumulation in brain and blood following systemic immune activation.

Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of L-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-D,L-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-D,L-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma L-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism.

3-Hydroxyanthranilic Acid↗
PubMed1994

Parkinsonism induced by solvent abuse.

We report the first description of a patient with parkinsonism induced by solvent abuse. Our patient developed parkinsonism acutely, following heavy abuse of lacquer thinner. Her clinical deficits were indistinguishable from idiopathic parkinsonism (Parkinson's disease) and she responded to levodopa. Parkinsonism has persisted for more than 3 months. Brain computed tomography was normal. Positron emission tomographic studies showed normal fluorodopa uptake and reduced raclopride binding, indicating an unusual disturbance of striatal dopaminergic function. This patient suggests that organic solvents may cause parkinsonism in susceptible individuals.

Administration, Inhalation↗
PubMed1994

Quantification of L-tryptophan and L-kynurenine by liquid chromatography/electron capture negative ion chemical ionization mass spectrometry.

In a number of infectious and inflammatory diseases, stimulation of the immune system can lead to increased accumulation of tryptophan metabolites via induction of kynurenine pathway enzymes in extrahepatic tissues. We developed a liquid chromatographic/mass spectrometric (LC/MS) method suitable for tracing the disposition of 13C isotopomers of L-tryptophan and L-kynurenine in various cultured cell, tissue slice, and whole animal model systems used to investigate tryptophan flux through the kynurenine pathway. The method employs extractive derivatization of the analytes and their 2H internal standards with pentafluorobenzyl bromide in order to enhance the negative ion chemical ionization (NICI) mass spectrometric response. Normal-phase liquid chromatographic separation of derivatized analytes was optimized using a silica column with organic solvents, followed by particle beam transfer and NICI-MS. Standard curves were linear over the range 1-250 ng per sample. Particle beam and mass spectrometric operating parameters were optimized with direct flow injections of 1-(methylamino) anthraquinone, which is an ideal test compound for the evaluation of LC/NICI-MS. The developed method was used to quantify the conversion of (13C6)L-tryptophan to (13C6)L-kynurenine by human monocytes (THP-1) stimulated with interferon-gamma, lung and brain tissue slices obtained from gerbils immune-stimulated with pokeweed mitogen. The effect of whole body immune stimulation on the plasma levels of endogenous L-kynurenine in mice stimulated with interferon-gamma was also quantified.

Animals↗
PubMed1993

Kynurenine 3-hydroxylase in brain: species activity differences and effect of gerbil cerebral ischemia.

We have developed a rapid and highly sensitive assay for brain kynurenine 3-hydroxylase activity. The present study determined some characteristics and species differences of kynurenine 3-hydroxylase activity in brain and evaluated the response of this enzyme to cerebral ischemia. The kynurenine 3-hydroxylase assay is based on the conversion of L-kynurenine to 3-hydroxykynurenine in vitro and the quantification of 3-hydroxykynurenine by high-performance liquid chromatography. Kynurenine 3-hydroxylase activity was detected in human, macaque, rat, mouse, and gerbil brain. Regional gerbil brain activities ranged from 20 to 50 nmol/g/h, while kynurenine 3-hydroxylase activities in other species were one order of magnitude lower. Kynurenine 3-hydroxylase was also detected in lung, kidney, spleen, intestine, and liver of gerbils, with activities larger than in brain. Delayed increases in the activity of kynurenine 3-hydroxylase occur in several brain regions following transient ischemia in gerbils. These changes are particularly marked in regions that showed the most extensive brain damage (hippocampus and striatum). Kynurenine 3-hydroxylase may have an important role in determining the flux of kynurenine in brain.

Animals↗
PubMed1993

L-deprenyl confers specific protection against MPTP-induced Parkinson's disease-like movement disorder in the goldfish.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the goldfish causes a reversible, Parkinson's disease-like syndrome which includes loss of noradrenaline and dopamine from the brain, accumulation of the toxic metabolite 1-methyl-4-phenylpyridinium species (MPP+), and substantial reduction in movement. L-Deprenyl, a selective monoamine oxidase-B inhibitor, protects the goldfish from loss of movement, but clorgyline, a selective monoamine oxidase-A inhibitor, has no such protective action. L-Deprenyl and clorgyline primarily inhibit goldfish brain monoamine oxidase-B and monoamine oxidase-A, respectively. The mechanism by which MPTP causes reduced movement in goldfish is to cause an increase in resting time. Otherwise normal average velocity occurred during periods of movement. L-Deprenyl protection results in entirely 'normal' levels of resting time and average velocity during times of movement. Equivalent observations regarding l-deprenyl and clorgyline have been made in primate models of MPTP toxicity, and l-deprenyl is used for treatment of Parkinson's disease in humans. Therefore it is suggested that the evolutionarily equivalent subcortical circuitry and neural density of the goldfish brain may provide a useful model upon which to search for drugs relevant to human Parkinson's disease.

Animals↗
PubMed1993

A mechanism for increased quinolinic acid formation following acute systemic immune stimulation.

Mechanisms for increased levels of quinolinic acid (QUIN) following systemic immune stimulation were investigated. In gerbils, systemic administration of pokeweed mitogen (PWM) increased plasma and cerebrospinal fluid QUIN levels, while plasma kynurenic acid levels were decreased and cerebrospinal fluid kynurenic acid levels were unchanged. PWM also increased the QUIN concentrations of brain and systemic tissues. In slices of spleen, lung, liver, duodenum, and kidney, PWM caused marked increases in [13C6]QUIN formation from L-[13C6]tryptophan (but not from [13C6]anthranilic acid). PWM also increased QUIN excretion in the urine and enhanced the formation and excretion of [13C6]QUIN following an intraperitoneal injection of L-[13C6]tryptophan. Indoleamine-2,3-dioxygenase activity was increased in the brain, kidney, lung, spleen, and duodenum while hepatic L-tryptophan-2,3-dioxygenase activity was reduced, data consistent with in vitro L-kynurenine formation from L-tryptophan. Kynurenine-3-hydroxylase activity was increased in the duodenum, lung, and spleen, but not in the brain, kidney, or liver. Kynureninase activity was increased in the brain, lung, and duodenum, but not in the spleen, kidney, or liver. 3-Hydroxyanthranilate-3,4-dioxygenase activity was unchanged in the brain, lung, and liver. No change in kynurenine aminotransferase activity was observed in the brain or lung, while liver kynurenine aminotransferase activity was reduced. We conclude that increased activities of kynurenine pathway enzymes in various tissues following systemic immune stimulation, in conjunction with macrophage infiltration of the affected tissue, provide a mechanism to account for increased concentrations of QUIN.

Animals↗
PubMed1993

4-Chloro-3-hydroxyanthranilate, 6-chlorotryptophan and norharmane attenuate quinolinic acid formation by interferon-gamma-stimulated monocytes (THP-1 cells).

Accumulation of quinolinic acid and L-kynurenine occurs in the brain and/or blood following immune activation, and may derive from L-tryptophan following induction of indoleamine 2,3-dioxygenase and other kynurenine-pathway enzymes. In the present study a survey of various cell lines derived from either brain or systemic tissues showed that, while all cells examined responded to interferon-gamma by increased conversion of L-[13C6]tryptophan into L-kynurenine (human: B-lymphocytes, neuroblastoma, glioblastoma, lung, liver, kidney; rat brain: microglia, astrocytes and oligodendrocytes), only macrophage-derived cells (peripheral-blood mononuclear cells; THP-1, U-937) and certain liver cells (SKHep1) synthesized [13C6]quinolinic acid. Tumour necrosis factor-alpha enhanced the effects of interferon-gamma in THP-1 cells. Norharmane, 6-chloro-DL-tryptophan and 4-chloro-3-hydroxyanthranilate attenuated quinolinic acid formation by THP-1 cells with IC50 values of 51 microM, 58 microM and 0.11 microM respectively. Norharmane and 6-chloro-DL-tryptophan attenuated L-kynurenine formation with IC50 values of 43 microM and 51 microM respectively, whereas 4-chloro-3-hydroxyanthranilate had no effect on L-kynurenine accumulation. The reductions in L-kynurenine and quinolinic acid formation are consistent with the reports that norharmane is an inhibitor of indoleamine 2,3-dioxygenase, 6-chloro-DL-tryptophan is metabolized through the kynurenine pathway, and 4-chloro-3-hydroxyanthranilate is an inhibitor of 3-hydroxyanthranilate 3,4-dioxygenase. These results suggest that many tissues may contribute to the production of L-kynurenine following indoleamine 2,3-dioxygenase induction and immune activation. Quinolinic acid may be directly synthesized from L-tryptophan in both macrophages and certain types of liver cells, although uptake of quinolinic acid precursors from blood may contribute to quinolinic acid synthesis in cells that cannot convert L-kynurenine into quinolinic acid.

3-Hydroxyanthranilic Acid↗
PubMed1993

A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate.

Quinolinic acid (QUIN), kynurenic acid (KYNA) and L-kynurenine (L-KYN) are neuroactive kynurenine pathway metabolites that accumulate in inflammatory neurological diseases. These increases were attributed to the induction of indoleamine-2,3-dioxygenase (IDO), the enzyme that converts L-tryptophan into L-KYN. Direct conversion of L-tryptophan into QUIN by brain tissue occurs in conditions of CNS inflammation, but not by normal brain tissue. To investigate whether increased activity of enzymes distal to IDO may determine L-KYN conversion to QUIN, rhesus macaques were inoculated with poliovirus directly into the spinal cord, as a model of focal inflammatory neurological disease (FASEB J. 6, 2977-2989, 1992). Induction of spinal cord IDO (35.9-fold) accompanied smaller, but proportional increases in kynurenine-3-hydroxylase (2.4-fold) and kynureninase (2.3-fold) activities, which were correlated to CSF and tissue QUIN levels, as well as to measures of inflammatory lesions. 3-Hydroxyanthranilate-3,4-dioxygenase activity was unchanged. Cerebrospinal fluid KYNA levels increased in proportion to both IDO activity and L-KYN accumulation, though kynurenine aminotransferase activity was unaffected. Cerebrospinal fluid neopterin, a marker of macrophage and immune activation, accumulated in proportion to the responsive enzymes and metabolites. The cell types involved in producing QUIN were investigated in vitro. Human foetal brain cultures consisting of astrocytes and neurons converted large quantities of [13C6]L-tryptophan into L-KYN when stimulated by gamma-interferon, but very little [13C6]QUIN was formed unless macrophages (THP-1 cells) were first added to the cultures (to model a key component of brain inflammation). [13C6]L-Tryptophan was converted into [13C6]QUIN by either gamma-interferon stimulated macrophages, or following intracisternal administration into poliovirus-infected macaques. Inhibitors of the kynurenine pathway, 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilic acid, attenuated [13C6]QUIN formation by macrophages, and when co-infused with [13C6]L-tryptophan into poliovirus-infected macaques. These results suggest roles for increased activities of IDO, kynurenine-3-hydroxylase and kynureninase in accelerating the synthesis of QUIN, L-KYN and KYNA in conditions of brain inflammation. Macrophage infiltrates, and perhaps microglia, are important sources of QUIN, whereas constitutive brain cells and macrophages are sources of L-KYN. Drugs that inhibit kynurenine pathway enzymes attenuate QUIN formation in the CNS, and provide tools to examine the consequences of reduced QUIN accumulation.

3-Hydroxyanthranilic Acid↗
PubMed1993

Quinolinic acid in the cerebrospinal fluid of children with symptomatic human immunodeficiency virus type 1 disease: relationships to clinical status and therapeutic response.

Quinolinic acid (QUIN) is a neurotoxin implicated in the neurologic deficits associated with human immunodeficiency virus type 1 (HIV-1) infection. Forty children with symptomatic HIV-1 disease had elevated (P < .001) cerebrospinal fluid (CSF) QUIN levels (55.8 +/- 8.9 nM) compared with controls (14.9 +/- 3.0 nM). Age-adjusted CSF QUIN concentrations in HIV-1-infected children were predicted by the general index of mental abilities (GIMA, from an age-appropriate intelligence test; r = -0.45, P < .01). Zidovudine therapy reduced CSF QUIN from 64.1 +/- 16.3 to 19.7 +/- 5.2 nM (P < .01; N = 16) and increased GIMA from 76.8 +/- 5.2 to 87.2 +/- 6.3 (P < .001). Encephalopathic HIV-1-infected patients had higher CSF QUIN levels than patients without encephalopathy (79.6 +/- 16.1 vs. 32.7 +/- 6.7 nM, P < .01). CSF QUIN concentrations were also higher (P < .001) in patients who died < or = 3 years after their baseline assessment, compared with those who were still alive. These results warrant further investigation of CSF QUIN in HIV-infected children as a mediator of neurologic dysfunction and a supplemental marker of neurologic disease, particularly when combined with measures of neurocognitive functioning.

AIDS Dementia Complex↗
PubMed1993

Mechanism of delayed increases in kynurenine pathway metabolism in damaged brain regions following transient cerebral ischemia.

Delayed increases in the levels of an endogenous N-methyl-D-aspartate receptor agonist, quinolinic acid (QUIN), have been demonstrated following transient ischemia in the gerbil and were postulated to be secondary to induction of indoleamine-2,3-dioxygenase (IDO) and other enzymes of the L-tryptophan-kynurenine pathway. In the present study, proportional increases in IDO activity and QUIN concentrations were found 4 days after 10 min of cerebral ischemia, with both responses in hippocampus > striatum > cerebral cortex > thalamus. These increases paralleled the severity of local brain injury and inflammation. IDO activity and QUIN concentrations were unchanged in the cerebellum of postischemic gerbils, which is consistent with the preservation of blood flow and resultant absence of pathology in this region. Blood QUIN and L-kynurenine concentrations were not affected by ischemia. Brain tissue QUIN levels at 4 days postischemia exceeded blood concentrations, minimizing a role for breakdown of the blood-brain barrier. Marked increases in the activity of kynureninase, kynurenine 3-hydroxylase, and 3-hydroxyanthranilate-3,4-dioxygenase were also detected in hippocampus but not in cerebellum on day 4 of recirculation. In vivo synthesis of [13C6]QUIN was demonstrated, using mass spectrometry, in hippocampus but not in cerebellum of 4-day postischemic animals 1 h after intracisternal administration of L-[13C6]tryptophan. However, accumulation of QUIN was demonstrated in both cerebellum and hippocampus of control gerbils following an intracisternal injection of 3-hydroxyanthranilic acid, which verifies the availability of precursor to both regions when administered intracisternally. Notably, although IDO activity and QUIN concentrations were unchanged in the cerebellum of ischemic gerbils, both IDO activity and QUIN content were increased in cerebellum to approximately the same degree as in hippocampus, striatum, cerebral cortex, and thalamus 24 h after immune stimulation by systemic pokeweed mitogen administration, demonstrating that the cerebellum can increase IDO activity and QUIN content in response to immune activation. No changes in kynurenic acid concentrations in either hippocampus, cerebellum, or cerebrospinal fluid were observed in the postischemic gerbils compared with controls, in accordance with the unaffected activity of kynurenine aminotransferase activity. Collectively, these results support roles for IDO, kynureninase, kynurenine 3-hydroxylase, and 3-hydroxyanthranilate-3,4-dioxygenase in accelerating the conversion of L-tryptophan and other substrates to QUIN in damaged brain regions following transient cerebral ischemia. Immunocytochemical results demonstrated the presence of macrophage infiltrates in hippocampus and other brain regions that parallel the extent of these biochemical changes.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxyanthranilic Acid↗
PubMed1993

Kynurenine pathway enzymes in brain: responses to ischemic brain injury versus systemic immune activation.

Accumulation of L-kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of L-[13C6]tryptophan to [13C6]-QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine-2,3-dioxygenase may determine whether L-kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3-hydroxy-3,4-dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine-2,3-dioxygenase and kynurenine-3-hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of QUIN, [13C6]anthranilic acid, was not converted to [13C6]QUIN in the hippocampus of either normal or 4-day post-ischemic gerbils. Gerbil macrophages stimulated by endotoxin in vitro converted L-[13C6]tryptophan to [13C6]QUIN. Kinetic analysis of kynurenine-3-hydroxylase activity in the cerebral cortex of postischemic gerbils showed that Vmax increased, without changes in Km. Systemic administration of pokeweed mitogen increased indoleamine-2,3-dioxygenase and kynureninase activities in the brain without significant changes in kynurenine-3-hydroxylase or 3-hydroxyanthranilate-3,4-dioxygenase activities. Increases in kynurenine-3-hydroxylase activity, in conjunction with induction of indoleamine-2,3-dioxygenase, kynureninase, and 3-hydroxyanthranilate-3,4-dioxygenase in macrophage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert L-[13C6]tryptophan to [13C6]QUIN.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1992

Organic ion imaging using tandem mass spectrometry.

A triple-quadrupole mass spectrometer has been interfaced with a wide-angle secondary ion microprobe. The combination permits acquisition of data necessary to determine the distribution of targeted organic analytes even in the presence of overwhelming isobaric interference. Micrographs generated from secondary ion intensity alone are compared to those generated using secondary ionization with tandem mass spectrometry (MS/MS), both for image reference and to show the improvement in image quality that can be attained when MS/MS is employed. Inhomogeneous mixtures of glycerol, KCl, and asparagine on 1-cm-diameter aluminum targets were used to demonstrate the instrument's selectivity. Secondary ions generated from samples of this system include isobaric 133Cs+ implanted from the primary ion beam, the 41K(+)-glycerol adduct, and protonated asparagine.

Asparagine↗