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Removal Characteristics of Immunoadsorption with the Tryptophan-Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis.

Autoimmune neurological diseases are often treated by immunoadsorption using a conventional plasma separator and tryptophan-immobilized column (IA). However, there is only one case report on treatment with immunoadsorption using a selective plasma separator and tryptophan-immobilized column (SeIA) in clinical practice. This study aimed to investigate the removal characteristics of antibodies against acetylcholine receptors (AChRAb), immunoglobulin G, fibrinogen, and factor XIII (FXIII) in IA and SeIA in four patients with myasthenia gravis. A total of 19 sessions of immunoadsorption were perfo…

Investigation of the aryl hydrocarbon receptor and the intrinsic tumoral component of the kynurenine pathway of tryptophan metabolism in primary brain tumors.

INTRODUCTION: There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. METHODS: We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptop…

Генетическая трансформация C. trachomatis Ocular Isolate с функциональным триптофаном Синтасе Operon Conferers a Indole-Safety Phenotype.

Хламидиотрахоматис является главной причиной предотвратимой слепоты и наиболее часто встречающейся бактериальной инфекции, передающей половым путем. Различные штаммы связаны с окулярными или врожденными инфекциями, и предложенным механизмом, который может объяснить этот тканевой тропизм, является активный биосинтезный путь триптофана, кодируемый геномным опероном ТрпРБА в врожденных штаммах. Здесь мы описываем генетические исследования по дополнению, которые необходимы для подтверждения роли триптофановой синтазы в контексте окулярного C. trachomatis геномного фона. Окулярный штамм A2497 был п

Совпадение в аннотации оригинала
Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Different strains are associated with ocular or urogenital infections, and a proposed mechanism that may explain this tissue tropism is the active tryptophan biosynthesis pathway encoded by the genomic trpRBA operon in urogenital …

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study.

BACKGROUND: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). METHODS: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP pati…

Photooxidation of Tryptophan and Tyrosine Residues in Human Serum Albumin Sensitized by Pterin: A Model for Globular Protein Photodamage in Skin.

Human serum albumin (HSA) is the most abundant protein in the circulatory system. Oxidized albumin was identified in the skin of patients su … howed that Ptr is able to photoinduce oxidation of the protein in at least two amino acid residues: tryptophan (Trp) and tyrosine (Tyr). HSA undergoes oligomerization, yielding protein structures whose molecular weight increases with irradiation time. The protein cross-linking, due to the formation of dimers of Tyr, does not significantly affect the secondar …

Serum tryptophan and kynurenine concentrations as parameters for indoleamine 2,3-dioxygenase activity in patients with endometrial, ovarian, and vulvar cancer.

OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is involved in immune escape of cancers. Indoleamine 2,3-dioxygenase catalyzes the initial rate-limiting step in the degradation of the essential amino acid tryptophan. In this study, we investigated cancer-induced IDO activity in sera of endometrial, ovarian, and vulvar cancer patients. METHODS: Concentrations of tryptophan and kynurenine were determined in pretreatment serum samples of patients with endometrial (n = 41), ovarian (n = 28), and vulvar cancer (n = 40) and compared to 19 healthy female con…

Role of serotonin transporter inhibition in the regulation of tryptophan hydroxylase in brainstem raphe nuclei: time course and regional specificity.

Drugs that selectively inhibit the serotonin transporter (SERT) are widely prescribed for treatment of depression and a range of anxiety disorders. We studied the time course of changes in tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague-Dawley rats received daily meals of rice pudding either alone (n=9) or mixed with citalopram 5 mg/kg/day (n=27). Rats were sacrificed after 24 h, 7 days or 28 days of treatment. Sections of dorsal raphe nucleus (DRN), median raphe nucleus (…

A case report of the efficient reduction of calcium channel antibodies by tryptophan ligand immunoadsorption in a patient with Lambert-Eaton syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular transmission disease caused by autoantibodies directed against voltage-gated calcium channels (VGCC). We report on a patient with LEMS and a cerebellar syndrome associated with lymphatic proliferation in the thymus. As thymectomy and immunosuppressive therapy failed to efficiently reduce clinical symptoms and VGCC antibody titer, we performed immunoadsorption using a tryptophan-ligand column for the first time. Repeated treatments resulted in a considerable decrease in antibody levels and a marked subjective and objective amelioration…

Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders.

Decision making, choosing the best option from the possible outcomes, is impaired in many psychiatric conditions including affective disorders. We tested the hypothesis that variations in serotonergic genes (TPH2, TPH1, SLC6A4, HTR1A), which influence serotonin availability, affect choice behavior in a probabilistic gambling task. A population cohort (N=1035) completed a paper-and-pencil gambling task, filled out personality and symptom questionnaires and gave consent for the use of their DNA in a genetic association study. A subgroup of subjects (N=69) also completed a computer version of the

Dynamic physiological and molecular changes in gastric ulcer healing achieved by melatonin and its precursor L-tryptophan in rats.

Following induction of gastric ulcer in rats by serosal application of acetic acid, local mucosal necrosis ensues accompanied by a reduction in mucosal microcirculation and by almost immediate expression of inducible nitric oxide (NO) synthase (iNOS) and proinflammatory cytokines. Daily application of melatonin (20 mg/kg) or l-tryptophan (100 mg/kg) accelerates ulcer healing by affecting the cyclooxygenase-2 (COX-2)-prostaglandin (PG) system with excessive production of protective PG, especially in later period of ulcer healing. Furthermore, expression of hypoxia inducible factor, vascular-end…

Randomized clinical assay for hepatic grafts preservation with University of Wisconsin or histidine-tryptophan-ketoglutarate solutions in liver transplantation.

University of Wisconsin (UW) solution has been the standard for preservation of liver transplantation grafts since 1989. However, some studies demonstrated that histidine-tryptophan-ketoglutarate (HTK) solution is also effective. The purpose of this study was to compare the efficacy of both solutions in liver transplantation. From January 2003 to August 2004 the livers of deceased donors were randomized into HTK and UW groups. The 102 studied patients included 65 (63.7%) in the UW group and 37 (36.3%) in the HTK group. Sex, race, hemodynamic state, use of adrenergic drugs, and presence of stea…

Tryptophan depletion does not modify response to CCK-4 challenge in patients with panic disorder after treatment with citalopram.

RATIONALE: Data by [Bell et al. J Psychopharmacol (2002) 16:5-14] suggest that a decrease in 5-HT neurotransmission predisposes to panic attacks and that the antipanic effect of SSRIs depends upon the availability of 5-HT in the brain. OBJECTIVES: Our aim was to assess the effect of acute tryptophan depletion (TD) on cholecystokinin-tetrapeptide (CCK-4)- induced symptoms in patients with panic disorder (PD) who had responded to a 10-week treatment with a selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram. MATERIALS AND METHODS: A total of 18 patients (6 males and 12 females, me…

The effects of a branched chain amino acid mixture supplemented with tryptophan on biochemical indices of neurotransmitter function and decision-making.

RATIONALE: We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function. OBJECTIVES: To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP. METHODS: We studied 32 healthy volunteers who were randomly…

Specific modification of two tryptophans within the nuclear-encoded subunits of bovine cytochrome c oxidase by hydrogen peroxide.

Hydrogen peroxide does more than react with the binuclear center of oxidized bovine cytochrome c oxidase and generate the well-characterized … trospray ionization mass spectrometry. In each case, the increased mass is caused by oxidation of a tryptophan (Trp19 within subunit VIIc and Trp48 within subunit IV), almost certainly due to formation of hydroxytryptophan. We conclude that hydrogen peroxide-induced oxidation of tryptophan and cardiolipin proceeds via the binuclear center since both modifica …

Role of the 5' untranslated region (UTR) in the tissue-specific regulation of rat tryptophan hydroxylase gene expression by stress.

There are tissue specific discrepancies in expression of tryptophan hydroxylase (TPH) between the pineal gland and brainstem. TPH mRNA levels in the pineal are much higher than in the brainstem, however, the two tissues contain comparable protein levels. This discrepancy could result from different translation efficiency of two of the TPH mRNA isoforms. Using PCR-based methods, we analyzed the relative expression, in pineal and brainstem, of two TPH mRNA isoforms differing in the length of their untranslated region (5'UTR). The levels of the TPHalpha were found to be 960-fold more abundant tha…

Replacing tryptophan-128 of T4 endonuclease V with a serine residue results in decreased enzymatic activity in vitro and in vivo.

Endonuclease V of bacteriophage T4 possesses two enzymatic activities, a DNA N-glycosylase specific for cyclobutane pyrimidine dimers (CBPD) and an associated apurinic/apyrimidinic (AP) lyase. Extensive structural and functional studies of endonuclease V have revealed that specific amino acids are associated with these two activities. Controversy still exists regarding the role of the aromatic amino acid stretch close to the carboxyl terminus, in particular the tryptophan at position 128. We have expressed wild-type and mutant W128S endonuclease V in Escherichia coli from an inducible tac prom…

Eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Analysis of four patients and implications for differential diagnosis and pathogenesis.

Four patients fulfilling the case definition for eosinophilia-myalgia syndrome are described, including one whose disease began in 1986. Each displayed a variety of symptoms: one suffered principally from myalgia and recovered spontaneously on discontinuation of L-tryptophan therapy; one exhibited progressive sclerodermiform skin changes, neuropathy, and myopathy; a third had prominent neuromuscular disease and sclerodermiform skin changes; and the fourth experienced profound weight loss, an axonal polyneuropathy, and perivascular lymphoid infiltrates simulating a lymphoma. Evidence of T-cell …

Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms.

We investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4-6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower trytophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-gamma and th…

Effects of carbohydrate and protein administration on rat tryptophan and 5-hydroxytryptamine: differential effects on the brain, intestine, pineal, and pancreas.

We compared the acute effects of intragastric administration of protein and carbohydrate on tryptophan and 5-hydroxytryptamine (5HT) in rat brain, pineal, intestine, and pancreas. Protein decreased and carbohydrate increased brain indoles relative to water-infused controls. These effects were due to competition between the large neutral amino acids for entry into the brain. This competition does not exist in the pineal. The macronutrients had no effect on pineal tryptophan metabolism. In the intestine, protein resulted in higher tryptophan levels as compared to controls, owing to absorption of…

Desipramine treatment in normal subjects. Effects on neuroendocrine responses to tryptophan and on platelet serotonin (5-HT)-related receptors.

Normal subjects took the tricyclic antidepressant, desipramine hydrochloride, for 16 days. Following treatment there was an increase in the number of specific binding sites on the platelet for both tritiated imipramine and tritiated LSD, the latter site probably representing a platelet serotonin (5-HT) receptor. During desipramine treatment the prolactin response to tryptophan (L-tryptophan) was enhanced, and this enhancement correlated with the increase in platelet LSD binding. The results confirm previous observations that desipramine administration increases certain 5-HT-mediated neuroendoc…