Wednesday, February 01, 2006

Why tryptophan is bad for people who have chemical imbalances related to histamine and serotonin.

This post is a continuation, with all the fine print, and gory pathological detail, of a post that starts at GMO Pundit as follows:

By a strange twist of fate, GMO Pundit is ideally placed to alert readers to a real hazard - excessive tryptophan intake in the wrong circumstances - that is widely misunderstood in the community, and is a previously falsely diagnosed risk.

The main point of this posting is to help people avoid ill health - that is avoid generalised muscular pains (myalgia, called EMS) - that might be caused by ill-advised self-medication with tryptophan, or excessive intake of foods rich in tryptophan. Such intake is commonly taken because it is perceived to help overcome mental depression caused by chemical imbalances in the brain.



Pundit also wants to get over the message that false information itself can cause harm by the distractions it creates that become red-herrings obscuring which are effective and most important safety precautions to be taken.

go to Tryptophan Risk confusion for the continuation of this story over at GMO Pundit.
go to 1.20—High Doses of Tryptophan Cause EMS at Academics Review for a readable short update on how this issue has been mis-used by Jeffrey M Smith  (March 2010)



While over at GMO Pundit, when you get to a link that brings you back here for further details, just click it.




The following are extensive quotations of relevant biological science, starting with the recent major medical review article by Smith and Garrett that explains how there has been a paradigm shift on concepts telated to EMS and similar diseases.

Some points that falsify the conjecture thay GM technology causes EMS are coded in Red. Point supporting other factors cause EMS are in Blue. Further points are obtainable in the original paper and in the extra quotes at GMO Pundit

At the end is an extensive literature citation list on the topic.


A heretofore undisclosed crux of Eosinophilia-Myalgia Syndrome [EMS] : compromised histamine degradation.

M. J. Smith1 and R. H. Garrett2 Infl ammation Research 54 (2005) 435–450
1 Division of Natural Products, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway,
College Park, Maryland 20740-3835, USA, Fax: ++ 301 436 2644, e-mail: mitchell.smith@cfsan.fda.gov
2 Department of Biology, University of Virginia, Charlottesville, Virginia, 22904-4328, USA, Fax: ++ 434 982 5626, e-mail: rhg@virginia.edu

In contrast to early epidemiological evidence offering links between eosinophilia-myalgia syndrome (EMS) and microimpurities of L-tryptophan-containing dietary supplements (LTCDS), this account shows why reliance on a finite impurity from one manufacturer is both unnecessary and insufficient to explain the etiology of EMS. Excessive histamine activity has induced blood eosinophilia and myalgia (Greek:mys, muscle + algos, pain). Termination of the multiple actions of histamine is dependent on particular amine oxidases and histamine-N-methyltransferase. Histamine metabolism is rapid when these degradative reactions are operative. The latent effects of incurred histamine can be potentiated and aggravating when these mechanisms are impaired. Overloads of tryptophan supplements cause – among other relevant side-effects – an increased formation of formate and indolyl metabolites, several of which inhibit the degradation of histamine. Moreover, (non-EMS) subjects with hypothalamic-pituitary-adrenal (HPA) axis dysregulation have also manifested greatly increased sensitivities to incurred tryptophan and histamine. A final common pathway for syndromes characterized by eosinophilia with myalgia is now evident.

Conclusions
A scientific tenet is undermined when the manifestations of a malady or outbreak are attributed – without ascertainable evidence – to a singular cause. Because a wide variety of agents and conditions can induce metabolic aberrations inextricably linked to compromised histamine degradation, reliance on a finite impurity as “the etiologic agent” [11, 34–36] is both unnecessary and insufficient to account for the key features of EMS.
At a minimum, over 20,000 consumers were seriously afflicted by eosinophilia with myalgia in the 1980s, and nearly 400 direct deaths have been recorded [2, 317].41 Above all, a wide spectrum of primary data converges at the etiologic junction where compromised histamine degradation, abnormal eosinophil counts and myopathy overlap — whereby histamine disequilibrium appears to be a final common pathway for syndromes characterized by eosinophilia with myalgia. Sattler and Lorenz [318] have outlined a “histaminosis” model of disease susceptibility based on histamine and incurred inhibitors of SSAO.
Processes that bring hazards, maladies and outbreaks to professional and public attention can create misperceptions about their root causes and true incidences. Misdiagnosis of histamine intoxication is common [118] and compromised histamine degradation is even less perceptible. Apprehensions that EMS-like disorders will continue to surface among unsuspected subpopulations are well-founded in light of several mechanisms (disclosed above) that greatly increase a subject’s sensitivities to incurred tryptophan and histamine.


J Neural Transm Suppl. 1990;32:291-314.
Intestinal diamine oxidases and enteral-induced histaminosis: studies on three prognostic variables in an epidemiological model.Sattler J, Lorenz W.
The danger of luminal histamine administered orally or formed in the intestinal fluid by bacteria has long been neglected. However, the demonstration of blocking intestinal diamine oxidase (DAO) by a variety of common drugs has revived the discussion and has created a new disease concept: enteral-induced histaminosis. In an animal model the three central prognostic variables of this disease concept (large amounts of histamine in food to make the individual ill, blocking of DAO by commonly used drugs, and the relationship between increased plasma histamine levels and disease manifestation by exogenous histamine application) were tested with randomized trials in vivo and biochemical tests in vitro using semipurified enzymes from pig and man. In the first trials authentic histamine in quantities similar to that in normal amounts of food or cheese bought from a supermarket produced life-threatening reactions if the DAO was inhibited by pretreatment with aminoguanidine. In the second series of experiments in vitro a numerous commonly used drugs was shown to inhibit both the porcine and human enzyme. Some of the inhibitors were really strong, such as dihydralazine, chloroquine, pentamidine, cycloserine, clavulanic acid, dobutamine, pancuronium and others. The type of inhibition was sometimes competitive as in the case of dihydralazine and pancuronium, sometimes non competitive (e.g. pentamidine) which may be important for long-term treatment.
In the third group of experiments a relationship between the dose of i.v. injected histamine and the elevation in plasma histamine levels and clinical symptoms in pigs was demonstrated. Hence, elevated plasma histamine in pigs acts as a pathogenetic factor for the disease manifestation. It is concluded that after modelling enteral-induced histaminosis in an animal the trias of variables shown in this study should be consequently investigated in man.


According to certain epidemiologists, “the available evidence provides a strong basis for concluding consumption of products containing tryptophan manufactured by Showa Denko caused the 1989 epidemic of EMS in the United States” [12]. Some medical dictionaries [13], websites2 and many investigators have favored such hypotheses, e. g., “Conclusions. The outbreak of EMS in 1989 resulted from the ingestion of a chemical constituent that was associated with specific tryptophan-manufacturing conditions at one company” [14]. With respect to studies offering links between EMS and tryptophan-manufacturing conditions at Showa Denko K.K., one epidemiological study emphasized: “the company used a fermentation process involving Bacillus amyloliquefaciens to manufacture tryptophan. In December 1988, the company introduced a new strain of B. amyloliquefaciens that increased the synthesis of serine and 5-phosphoribosyl-1-pyrophosphate, which are intermediates in the biosynthesis of tryptophan. This new strain (Strain V) was used for the manufacture of tryptophan after December 25, 1988” [14].

Innumerable investigations worldwide have attempted to resolve the precise cause(s) of eosinophilia with myalgia.3 As yet, few molecular breakthroughs have emerged. Pervasive hypothesis, two alleged (and partially interrelated) cofactors – namely, genetic engineering and a microimpurity/ies of dietary supplements [15] – are both unnecessary and insufficient explanations of enigmatic (multifactorial)4 chains of causality underlying a majority of official EMS cases.
Numerous etiologic incongruities [16–19]

[16] Blauvelt A, Falanga V. Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Arch Dermatol 1991; 127: 1159–66.
[17] Spry CJF. Eosinophils: A Comprehensive Review, and Guide to the Scientifi c and Medical Literature. Oxford, U.K.: Oxford University Press, 1988: 1–484.
[18] Goronzy JJ, Weyand CM. Eosinophilia, myopathy, and neuropathy in a patient with repeated use of L-tryptophan. Klin Wochenschr 1990; 68: 735–8.
[19] Kaufman LD. Neuromuscular manifestations of the L-tryptophanassociated eosinophilia-myalgia syndrome. Curr Opin Rheumatol 1990; 2: 896–900.



– including two reports of L-tryptophan-induced eosinophilia with myalgia in 1986 [20–22] – underscore why a paradigm shift was advisable.

[20] Strongwater SL, Woda BA, Yood RA, Rybak ME, Sargent J, De-
Girolami U et al. Eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Analysis of four patients and implications for differential diagnosis and pathogenesis. Arch Intern Med 1990; 150: 2178–86.

[21] Lakhanpal S, Duffy J, Engel AG. Eosinophilia associated with perimyositis and pneumonitis. Mayo Clin Proc 1988; 63: 37–41.
[22] Martin RW, Duffy J, Engel AG, Lie JT, Bowles CA, Moyer TP et al. The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology. Ann Intern Med 1990; 113:124–34


According to several analytical surveys, incriminated tryptophan met Pharmacopeia criteria (DAB 9) for products intended for medicinal purposes in Germany [23]. LTCDS [Diet with tryptophan supplement] incriminated in the U.S. were Pharmacopoeia grade also [11]; aside from one internally incongruent outlier about inorganic impurities [24], no known data undercut widespread evidence that other incriminated case lots had ananalytical purity of 98.5%5 or higher [5, 7, 25–27]. Analysis of other incriminated case lots disclosed purities of 99.6%, which meet Japanese Pharmacopoeia specifications [28–30].
Thus, the quantities of adulterants in incriminated LTCDS remained exceedingly low – 650 ppm for the most prevalent (confirmed) impurity [31] – according to virtually all ascertainable evidence.

Additional counterevidence from Waller, Wood, Breckenridge and Rawlins, (published by the London Department of Health and Social Security) disclosed at least 3 official6 EMS cases in the United Kingdom that were associated with a Merck pharmaceutical product containing L-tryptophan (Optimax)7 [32]. An analogous survey in Ireland disclosed 5 cases of eosinophilia linked to Optimax [33]. These little known landmarks do not comport with hypotheses that “the etiologic agent” [11, 34–36] of L-tryptophan-induced EMS is a finite microimpurity/ies of LTCDS manufactured by Showa Denko K.K.

As the proceedings of a symposium devoted to EMS amply illustrate (J Rheumatol 1996; 23 (Suppl 46): 1–110), epidemiological data implicating finite microimpurities from one manufacturer are controversial and understandably so. One should be mindful of six incontestable facts that collectively undercut unifactorial explanations of an epidemiologic spike [37, 38] in recorded cases of eosinophilia with myalgia in the late 1980s: the stringent surveillance criteria devised for case-control studies were never meant to be employed as diagnostic criteria [11]; a U.S. Food and Drug Administration (FDA) nationwide recall and import alert in November 1989 for LTCDS in which L-tryptophan is the sole or major component [39]; a preceding “sharp upturn” [40] in nationwide consumption of L-tryptophan supplements [41, 42]; an inconsistent incidence among subjects who consumed L-tryptophan from common bottles [43]; a relatively low yet telling apparent incidence (vis-à-vis stringent criteria compounded by host susceptibility; see the penultimate Section) [44]; and lastly, analytical determinations of blood cell counts remain unmonitored in most medical checkups.


Aust N Z J Psychiatry. 1988 Mar;22(1):83-97. L-tryptophan: a rational anti-depressant and a natural hypnotic? Boman B.
L-tryptophan is an essential amino acid which is the metabolic precursor of serotonin. Because of the evidence that serotonin deficiency may be an aetiological factor in some sorts of affective disorder and that serotonin is important in the biochemistry of sleep, L-tryptophan has been suggested as a "rational" anti-depressant and as a "natural" hypnotic. This paper reviews the
biochemistry and pharmacology of L-tryptophan as well as the literature of the clinical trials that have been conducted with it and suggests that, by itself, L-tryptophan may be useful in mild cases of depression accompanied by endogenous features and cases of bipolar disorder resistant to standard treatments. It also potentiates the monoamine oxidase inhibitors and possibly the serotonergic tricyclic drugs. L-tryptophan may improve the depressed mood of Parkinsonian patients and has a clinically useful hypnotic action. There is evidence it may be useful in organic mental disorders induced by levodopa. Dosage schedules, contraindications and complications are discussed.


primarily because of implied benefits that might be accrued if certain indoleamines were to be augmented; cf. the serotonin hypothesis of affective disorders [102].

Dis Nerv Syst. 1977 Aug;38(8):646-53. The indoleamine hypothesis of depression: an overview and pilot study. Zarcone VP Jr, Berger PA, Brodie KH, Sack R, Barchas JD.

This paper reviews the evidence for a specific indoleamine deficiency in depression and the attempts to correct this suspected deficiency with serotonin precursors. It also presents the clinical and biochemical data on six patients with depression treated with L-5-HTP in a nonrandom, double-blind protocol. The oral administration of L5-HTP was associated with a rise in CSF5-HIAA, but only two of six patients studied had any decrease in depression ratings. 5-HTP was also shown to decrease urinary excretion of 17 hydroxycorticosteroids in twodepressed patients and three normal controls suggesting an interrelationship between serotonin metabolism and the pituitary adrenal system. This leads to the suggestion that in a postulated subgroup of depressed patients with pituitary adrenal hyperactivity and evidence of serotonin deficiency, L5-HTP deserves a further trial as an experimental treatment.


According to several epidemiologists, host susceptibility bias (among other little-known shortcomings) [46, 264, 303, 311–316] undercut the few case-control studies on EMS performed; hence, statistical (epidemiological) underpinnings purportedly supporting a contaminant theory’s primacy as well.

[46] Shapiro S. Epidemiologic studies of the association of L-tryptophan with the eosinophilia-myalgia syndrome: a critique. JRheumatol Suppl 1996; 46: 44–58; discussion 58–9.
In 1989 and 1990, 2 reports of a new disease labeled the eosinophilia-myalgia syndrome (EMS) and attributed to L-tryptophan (LT) were published. In subsequent studies a putative contaminant was implicated. In this review the following studies are considered: the initial 2 reports of the overall association, one report of an association between LT and eosinophilic fasciitis, and one report describing the scale of the apparent epidemic of LT induced EMS. Of the 2 initial studies, one included previously reported exposed cases, failed to rule out the possibility that early symptoms of EMS could have caused LT use rather than the reverse, and failed to adhere to the methods, as published. The 2nd study has not been published in a peer reviewed journal. The study of eosinophilic fasciitis was subject to information bias and misclassification of the timing of LT use. The apparent epidemic could have been an artefact of waxing and waning enthusiasm for reporting exposed cases to an EMS registry, corresponding with the timing and the amount of publicity given to the topic. The questionable validity of these studies considerably weakens the claim that LT or a contaminant caused EMS.


[264] Daniels SR, Hudson JI, Horwitz RI. Epidemiology of potential association between L-tryptophan ingestion and eosinophilia-myalgia syndrome. J Clin Epidemiol 1995; 48: 1413–27; discussion 1429–40.

This article examines the methodology of the epidemiological studies of the association between L-tryptophan and eosinophilia-myalgia syndrome (EMS) and evaluates the validity of the conclusions from these studies. In the initial case-control studies of L-tryptophantryptophan and EMS there were a variety of methodological problems, including different sources and different exclusion criteria for cases and controls, which could have resulted in selection bias, as well as problems with information bias and confounding. The studies of manufacturer and brand also had similar potential for bias. The L-tryptophan-EMS association is based on two small studies that had important methodological inadequacies. Subsequent studies of brand of L-tryptophan also contained errors in design, which may have produced biased results and call the conclusions into question. The cause of eosinophilia-myalgia syndrome remains unknown.

[303] Shapiro S. L-tryptophan and eosinophilia-myalgia syndrome.Lancet 1994; 344: 817–9.

[311] Spitzer WO, Haggerty JL, Berkson L, Davis W, Palmer W, Tamblyn R et al. Continuing occurrence of eosinophilia myalgia syndrome in Canada. Br J Rheumatol 1995; 34: 246–51.

Eosinophilia myalgia syndrome (EMS), was defined by the Centers for Disease Control (CDC) as eosinophilia > 1000 mm3 and incapacitating myalgia without infection or neoplasm. Studies suggested that use of L-tryptophan (L-T), was a risk factor. We conducted a pharmacoepidemiological survey in Canada where access to L-T is limited. Using the active surveillance method, a 100% sample of potentially involved specialists and a 15% sample of family physicians from Ontario and Quebec were surveyed regarding treatment of patients with severe myalgia within the past year. Follow-up amplified clinical and laboratory information. Overall response rates were 61.4%. Thirty-eight per cent of respondents reported at least one patient. Of 6423 patients assessed, 19 'definite' and 25 'possible' EMS cases were identified. Information from physicians did not suggest use of L-T in patients with definite or possible EMS. It was considered that the cases found an underestimate of the incidence of EMS. Its continuing occurrence in Canada brings causal interpretations of earlier studies into question.

[312] Spitzer WO, Haggerty JL, Berkson L, Davis W, Palmer W, Tamblyn R et al. Analysis of Centers for Disease Control and Prevention criteria for the eosinophilia-myalgia syndrome in a geographically defi ned population. J Rheumatol Suppl 1996; 46: 73–9; discussion 79–80. 1: J Rheumatol Suppl. 1996 Oct;46:73-9; discussion 79-80.

OBJECTIVE: To test whether individuals can be identified in a geographically defined population who would meet criteria for the eosinophilia-myalgia syndrome (EMS) established by the US Centers for Disease Control and Prevention (CDC), i.e, (1) eosinophil count > 1 x 10(9)/l, (2) myalgia severe enough to limit usual activities of daily living, and (3) no evidence of infection or neoplasm that could explain the first 2 findings. METHODS: To discover the number of individuals who would meet CDC criteria, the population was exhaustively searched using methods adapted from active pharmacoepidemiologic surveillance.
Medical consultants and primary care practitioners were questioned as many as 5 times in a search for patients with severe myalgia. A predetermined protocol was used to screen those patients who appeared to meet CDC criteria for EMS using active surveillance methods. The study population was limited to Quebec and Ontario (combined population 18,980,000) with special attention to the period July 1, 1992, to June 30, 1993. RESULTS: The prevalence of severe incapacitating myalgia was 43 per 100,000 persons, including 19 individuals with eosinophilia > 1 x 10(9)/l, who met CDC criteria for EMS. None of these individuals were reported to have taken L-tryptophan (LT). CONCLUSION: The CDC criteria for EMS are met by individuals in the general population who have never been exposed to LT.

[313] Hudson JI, Pope HG Jr, Daniels SR, Horwitz RI. Eosinophiliamyalgia
syndrome or fibromyalgia with eosinophilia? JAMA
1993; 269: 3108–9.

[314] Shapiro S. Comment. J Rheumatol Suppl 1996; 23: 89–91.

[315] Shapiro S. L-tryptophan and eosinophilia-myalgia syndrome.
Lancet 1994; 343: 1035–7.
[316] Horwitz RI, Daniels SR. Bias or biology: evaluating the epidemiologic
studies of L-tryptophan and the eosinophilia-myalgia
syndrome. J Rheumatol Suppl 1996; 46: 60–72.

Department of Medicine and Epidemiology, Yale University School of Medicine, New
Haven, Connecticut 06520-8056, USA.

When investigating the cause of a chronic disease, epidemiologists are forced to substitute observational, nonexperimental methods such as cohort or case-control studies for the scientifically preferred "gold standard," the randomized controlled trial. Because neither cohort nor case-control studies are done under experimental conditions, the results may not accurately reflect those that would be found in a randomized experiment. Before the results of epidemiologic research can be used for inference regarding a cause of disease, it is necessary to examine the design and conduct of such studies to ensure their results could not have been distorted by potential sources of bias. We evaluate the epidemiologic studies of the relationship between intake of L-tryptophan (LT) and the occurrence of eosinophilia-myalgia syndrome (EMS) from information provided in the published reports and underlying data and documentation of the studies obtained from the US Centers for Disease Control and state health departments. We reviewed separately the initial 2 studies that examined the link between LT and the risk for EMS and the subsequent studies that focused on the specific manufacturing process or chemical constitutents of LT that might have been responsible for EMS. The 2 initial studies compared cases of EMS with controls who were asymptomatic. The investigators concluded that ingestion of LT was associated with the occurrence of EMS. However, these studies contained methodologic problems, including diagnostic bias, publicity, recall and reporting bias, bias in the inclusion and exclusion of cases and controls, inequalities between cases and controls in the indications for the use of LT, and failure to ensure that the exposure to LT preceded the onset of symptoms of EMS. These potential biases make it difficult to use the data derived from these investigations to justify a causal inference. Subsequent studies were conducted under the assumption that there was a valid association between ingestion of LT and the occurrence of EMS. These studies focused on tracing back LT to the manufacturer. These studies also had a variety of methodologic shortcomings, including problems in the assembly of study subjects leading to the selected samples of cases and controls, the lack of information on the brand and lot of LT for many subjects, multiple brand use, differences in the timing of exposure between cases and controls, the difficulty of the process of tracing LT products to the appropriate manufacturer, inconsistent classification of symptoms depending on brand of LT used, and inconsistencies in the traceback procedures between cases and controls. In light of these analyses, it appears that the cause of EMS has not been definitively identified. The search for the cause of EMS should continue without the underlying assumption that LT or some contaminant is responsible.


( Many thanks to R Roush, A. Apel, and A. Avery for the original reference heads-up)

The Full Monty on tryptophan EMS references
A heretofore undisclosed crux of Eosinophilia-Myalgia Syndrome: compromised histamine degradation
M. J. Smith and R. H. Garrett Inflamm. res. 54 (2005) 435–450

Collected other references (from above review) provide the Full Monty on tryptophan and EMS:

References
[1] Toxic Epidemic Syndrome Study Group. Toxic epidemic syndrome,
Spain, 1981. Toxic Epidemic Syndrome Study Group.
Lancet 1982; 2: 697–702.
[2] Shulman LE. The eosinophilia-myalgia syndrome associated with
ingestion of L-tryptophan. Arthritis Rheum 1990; 33: 913–7.
[3] Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR,
Bjornson BH. NIH conference. The idiopathic hypereosinophilic
syndrome. Clinical, pathophysiologic, and therapeutic considerations.
Ann Intern Med 1982; 97: 78–92.
[4] Spry CJ. The hypereosinophilic syndrome: clinical features, laboratory
fi ndings and treatment. Allergy 1982; 37: 539–51.
[5] Hertzman PA, Falk H, Kilbourne EM, Page S, Shulman LE. The
eosinophilia-myalgia syndrome: the Los Alamos Conference. J
Rheumatol 1991; 18: 867–73.
[6] Anonymous commentary. Eosinophilia-Myalgia Syndrome-New
Mexico. MMWR Morb Mortal Wkly Rep 1989; 38: 765–7.
[7] Raphals P. Disease puzzle nears solution. Science 1990; 249: 619.
[8] Anonymous commentary. Toxic Oil Syndrome and Eosinophilia-
Myalgia Syndrome: Pursuing Parallels in Pathogenesis. Report
on a WHO Meeting,Washington, DC, May 8–10, 1991. WHO Regional
Offi ce for Europe, Copenhagen: EUR/HFA target 22, 1991:
1–22.
[9] D’Arcy PF. L-Tryptophan: eosinophilia-myalgia syndrome. Adverse
Drug React Toxicol Rev 1995; 14: 37–43.
[10] Ahmad SR, Clauw D. USA: EMS and L-Tryptophan. Lancet 1991;
338: 1512.
[11] Kaufman LD, Philen RM. Tryptophan. Current status and future
trends for oral administration. Drug Saf 1993; 8: 89–98.
[12] Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced
by Showa Denko and epidemic eosinophilia-myalgia syndrome.
J Rheumatol Suppl 1996; 46: 81–8; discussion 89–91.
[13] Anonymous Commentary. Taber’s Cyclopedic Medical Dictionary.
Philadelphia: F. A. Davis, 1993: 1–2590.
[14] Belongia EA, Hedberg CW, Gleich GJ, White KE, Mayeno AN,
Loegering DA et al. An investigation of the cause of the eosinophilia-
myalgia syndrome associated with tryptophan use. N Engl
J Med 1990; 323: 357–65.
[15] Aldhous P. Biotechnology. Yellow light on L-tryptophan. Nature
1991; 353: 490.
[16] Blauvelt A, Falanga V. Idiopathic and L-tryptophan-associated
eosinophilic fasciitis before and after L-tryptophan contamination.
Arch Dermatol 1991; 127: 1159–66.
[17] Spry CJF. Eosinophils: A Comprehensive Review, and Guide to the
Scientifi c and Medical Literature. Oxford, U.K.: Oxford University
Press, 1988: 1–484.
[18] Goronzy JJ, Weyand CM. Eosinophilia, myopathy, and neuropathy
in a patient with repeated use of L-tryptophan. Klin Wochenschr
1990; 68: 735–8.
[19] Kaufman LD. Neuromuscular manifestations of the L-tryptophanassociated
eosinophilia-myalgia syndrome. Curr Opin Rheumatol
1990; 2: 896–900.
[20] Strongwater SL, Woda BA, Yood RA, Rybak ME, Sargent J, De-
Girolami U et al. Eosinophilia-myalgia syndrome associated with
L-tryptophan ingestion. Analysis of four patients and implications
for differential diagnosis and pathogenesis. Arch Intern Med 1990;
150: 2178–86.
[21] Lakhanpal S, Duffy J, Engel AG. Eosinophilia associated with
perimyositis and pneumonitis. Mayo Clin Proc 1988; 63: 37–41.
[22] Martin RW, Duffy J, Engel AG, Lie JT, Bowles CA, Moyer TP et
al. The clinical spectrum of the eosinophilia-myalgia syndrome
associated with L-tryptophan ingestion. Clinical features in 20 patients
and aspects of pathophysiology. Ann Intern Med 1990; 113:
124–34.
[23] Jork H, Ganz J. Opportunities and limitations of modern TLC/
HPTLC in the quality control of L-tryptophan. L-Tryptophan Current
Prospects in Medicine and Drug Safety. Berlin: de Gruyter,
1994: 338–49.
[24] Caston JC, Roufs JB, Forgarty CM, Applebaum ML, Smith WP
Jr., Littlefi eld RH. Treatment of refractory eosinophilia-myalgia
syndrome associated with the ingestion of L-tryptophan containing
products. Adv Ther 1990; 7: 206–28.
[25] Simat T, van Wickern B, Eulitz K, Steinhart EH. Contaminants in
biotechnologically manufactured L-tryptophan. J Chromatogr B
Biomed Appl 1996; 685: 41–51.
[26] Varga J, Uitto J, Jimenez SA. The cause and pathogenesis of
the eosinophilia-myalgia syndrome. Ann Intern Med 1992; 116:
140–7.
[27] Bridgen P. L-Tryptophan-Health Problems, Production and Regulatory
Status: Proceedings of a Congressional Research Service
(CRS) Seminar. CRS Report for Congress, 91–758 SPR. Washington,
DC: Congressional Research Service, Oct. 15, 1991: 1–44.
[28] Chiba S, Miyagawa K, Tanaka T, Moriya K, Takahashi K, Hirai H
et al. Tryptophan-associated eosinophilia-myalgia syndrome and
pancreatitis. Lancet 1990; 336: 121.
[29] Newton P. High performance liquid chromatography and the mystery
of L-tryptophan. LC•GC 1990; 9: 208–13.
[30] Broide DH. Eosinophilia-myalgia syndrome. West J Med 1991;
154: 459.
[31] Simat TJ, Kleeberg KK, Muller B, Sierts A. Synthesis, formation,
and occurrence of contaminants in biotechnologically manufactured
L-tryptophan. Adv Exp Med Biol 1999; 467: 469–80.
[32] Waller P, Wood S, Breckenridge A, Rawlins M. Eosinophiliamyalgia
syndrome associated with prescribed L-tryptophan in the
United Kingdom. Health Trends 1991; 23: 53–5.
[33] McKeon P, Swanwick G, Manley P. L-tryptophan and the eosinophilia-
myalgia syndrome: a clinical and laboratory study. Acta
Psychiatr Scand 1994; 90: 451–4.
[34] Belongia EA, Mayeno AN, Osterholm MT. The eosinophilia-myalgia
syndrome and tryptophan. Annu Rev Nutr 1992; 12: 235–56.
[35] Kamb ML, Jones JL, Kilbourne EM, Falk H. [Reply to] Eosinophilia-
Myalgia Syndrome or Fibromyalgia with Eosinophilia?
JAMA 1993; 269: 3108–9.
[36] Back EE, Henning KJ, Kallenbach LR, Brix KA, Gunn RA, Melius
JM. Risk factors for developing eosinophilia myalgia syndrome
among L-tryptophan users in New York. J Rheumatol 1993; 20:
666–72.
[37] Anonymous commentary. Update: eosinophilia-myalgia syndrome
associated with ingestion of L-tryptophan-United States, as of
January 9, 1990. MMWR Morb Mortal Wkly Rep 1990; 39: 14–5.
[38] Swygert LA, Maes EF, Sewell LE, Miller L, Falk H, Kilbourne
EM. Eosinophilia-myalgia syndrome. Results of national surveillance.
JAMA 1990; 264: 1698–703.
[39] Anonymous commentary. Eosinophilia-myalgia syndrome and Ltryptophan-
containing products-New Mexico, Minnesota, Oregon,
and New York, 1989. MMWR Morb Mortal Wkly Rep 1989; 38:
785–8.
[40] Fuller RW. Role of serotonin in therapy of depression and related
disorders. J Clin Psychiatry 1991; 52 Suppl: 52–7.
[41] Duffy J. The lessons of eosinophilia-myalgia syndrome. Hosp
Pract (Off Ed) 1992; 27: 65–9, 73–80, 83–90.
[42] Simat T, Steinhart H, Kochen W. The Tryptophan Case an Overview.
L-Tryptophan Current Prospects in Medicine and Drug
Safety. Berlin: de Gruyter, 1994: 3–15.
[43] Hertzman PA. The eosinophilia-myalgia syndrome: opportunities
realized and missed. J Rheumatol 1996; 23: 1679–81.
[44] Carr L, Ruther E, Berg PA, Lehnert H. Eosinophilia-myalgia
syndrome in Germany: an epidemiologic review. Mayo Clin Proc
1994; 69: 620–5.
[45] Horton R. The refi guration of medical thought. Lancet 2000; 356:
2–4.
[46] Shapiro S. Epidemiologic studies of the association of L-tryptophan
with the eosinophilia-myalgia syndrome: a critique. J
Rheumatol Suppl 1996; 46: 44–58; discussion 58–9.
[47] Taylor S. Histamine food poisoning: toxicology and clinical aspects.
CRC Crit Rev Toxicol 1986; 17: 91–128.
[48] Walz LeBlanc BA, Inman RD. Eosinophilia-myalgia syndrome-old
questions for a new syndrome. J Rheumatol 1990; 17: 1435–8.
[49] Taylor MR. Regulation of Dietary Supplements. Federal Register
1993; 58: 33690–700.
[50] Kaufman LD. The eosinophilia-myalgia syndrome and related disorders.
Recenti Prog Med 1991; 82: 286–90.
[51] Smith SA, Roelofs RI, Gertner E. Microangiopathy in the eosinophilia-
myalgia syndrome. J Rheumatol 1990; 17: 1544–50.
[52] Smith SA. Pathology of the microangiography and immunohistochemistry
of the infl ammatory infi ltrate in eosinophilia-myalgia
syndrome. L-Tryptophan Current Prospects in Medicine and Drug
Safety. Berlin: de Gruyter, 1994: 223–33.
[53] Sy WM, Bay R, Camera A. Hand images: normal and abnormal. J
Nucl Med 1977; 18: 419–24.
[54] Shulman LE. The eosinophilia-myalgia syndrome associated with
ingestion of L-tryptophan. Arthritis Rheum 1990; 33: 913–7.
[55] Claman HN. On scleroderma. Mast cells, endothelial cells, and
fi broblasts. JAMA 1989; 262: 1206–9.
[56] Sjoerdsma A, Udenfriend S, Keiser H, LeRoy EC. Hydroxyproline
and collagen metabolism. Clinical implications. Ann Intern Med
1965; 63: 672–94.
[57] Claman HN. Mast cells, T cells and abnormal fi brosis. Immunol
Today 1985; 6: 192–5.
[58] Abe M, Kurosawa M, Ishikawa O, Miyachi Y. Effect of mast cellderived
mediators and mast cell-related neutral proteases on human
dermal fi broblast proliferation and type I collagen production. J
Allergy Clin Immunol 2000; 106: S78–84.
[59] Athens JW. Eosinophils and basophils. Wintrobe’s Clinical Hematology.
Philadelphia: Lea & Febiger, 1993: 299–310.
[60] Archer GT. The function of the eosinophil. Bibl Haematol 1968;
29: 71–85.
[61] Sato E, Haniuda M, Numanami H, Ushiyama T, Tsukadaira A,
Takashi S et al. Histamine and serotonin stimulate eotaxin production
by a human lung fi broblast cell line. Int Arch Allergy Immunol
2002; 128 Suppl 1: 12–7.
[62] MacDonald RA, Robbins SL, Mallory GK. Dermal fi brosis following
subcutaneous injections of serotonin. Proc Soc Exp Biol Med
1958; 97: 334–7.
[63] Wize J, Wojtecka-Lukasik E, Maslinski S. Collagen-derived peptides
release mast cell histamine. Agents Actions 1986; 18: 262–5.
[64] Beaven MA. Histamine: its role in physiological and pathological
processes. Monogr Allergy 1978; 13: 1–113.
[65] Dabrowski R, Maslinski C, Gorski P. The effects of histamine liberators
and exogenous histamine on wound healing in rat. Agents
Actions 1975; 5: 311–4.
[66] Fernex M. The Mast-Cell System. Baltimore, MD: Williams &
Wilkins, 1968: 1–212.
[67] Costa JJ, Galli SJ, Wershil BK. Mast cells and basophils: Basic biology
and roles in gastrointestinal diseases. Food Hypersensitivity
and Adverse Reactions. New York: Marcel Dekker, 1999: 1–38.
[68] Kaufman LD, Seidman RJ, Phillips ME, Gruber BL. Cutaneous
manifestations of the L-tryptophan-associated eosinophilia-myalgia
syndrome: a spectrum of sclerodermatous skin disease. J Am
Acad Dermatol 1990; 23: 1063–9.
[69] Silver RM, Heyes MP, Maize JC, Quearry B, Vionnet-Fuasset M,
Sternberg EM. Scleroderma, fasciitis, and eosinophilia associated
with the ingestion of tryptophan. N Engl J Med 1990; 322:
874–81.
[70] Oursler JR, Farmer ER, Roubenoff R, Mogavero HS, Watson RM.
Cutaneous manifestations of the eosinophilia-myalgia syndrome.
Br J Dermatol 1992; 127: 138–46.
[71] Gruber BL, Kaufman LD. Ketotifen-induced remission in progressive
early diffuse scleroderma: evidence for the role of mast cells
in disease pathogenesis. Am J Med 1990; 89: 392–5.
[72] Dickman S. Tough mining. The challenge of searching the scientifi
c literature. PLoS Biology 2003; 1: 144–7.
[73] Swanson DR. A second example of mutually isolated medical literatures
related by implicit, unnoticed connections. J Am Soc Inf
Sci 1989; 40: 432–5.
[74] Swanson DR. Medical literature as a potential source of new
knowledge. Bull Med Libr Assoc 1990; 78: 29–37.
[75] Taylor R, McNeil JJ. Eosinophilia-myalgia syndrome: lessons for
public health researchers. Med J Aust 1993; 158: 51–5.
[76] Platt JR. Strong inference. Science 1964; 146: 347–53.
[77] Moon VH, Lieber MM, Kennedy PJ. Histamine and leukocytosis.
Arch Pathol 1935; 20: 209–15.
[78] Weiss S, Robb GP, Ellis LB. The systemic effects of histamine in
man. Arch Int Med 1932; 360–96.
[79] Code CF, Hurn MM, Mitchell RG. Histamine in human disease.
Mayo Clin Proc 1964; 39: 715–37.
[80] Vaughn J. The function of the eosinophile leukocyte. Blood 1953;
8: 1–15.
[81] Poluektova LY, Khan MM. Protein kinase A inhibitors reverse histamine-
mediated regulation of IL-5 secretion. Immunopharmacology
1998; 39: 9–19.
[82] Schmidt J, Fleissner S, Heimann-Weitschat I, Lindstaedt R, Szelenyi
I. Histamine increases anti-CD3 induced IL-5 production of TH2-type
T cells via histamine H2-receptors. Agents Actions 1994; 42: 81–5.
[83] Khan MM. Regulation of IL-4 and IL-5 secretion by histamine and
PGE2. Adv Exp Med Biol 1995; 383: 35–42.
[84] Owen WF Jr, Petersen J, Sheff DM, Folkerth RD, Anderson RJ,
Corson JM et al. Hypodense eosinophils and interleukin 5 activity
in the blood of patients with the eosinophilia-myalgia syndrome.
Proc Natl Acad Sci USA 1990; 87: 8647–51.
[85] Clark RA, Gallin JI, Kaplan AP. The selective eosinophil chemotactic
activity of histamine. J Exp Med 1975; 142: 1462–76.
[86] Turnbull LW, Kay AB. Eosinophils and mediators of anaphylaxis.
Histamine and imidazole acetic acid as chemotactic agents for human
eosinophil leucocytes. Immunology 1976; 31: 797–802.
[87] Demis DJ, Davis MJ, Lawler JC. A study of the cutaneous effects
of serotonin. J Invest Derm 1960; 34: 43–50.
[88] Douglas WW. Autacoids. Goodman and Gilman’s The Pharmacolgical
Basis of Therapeutics.Macmillan Publ, 1985: 604–59.
[89] Keele CA. Chemical causes of pain and itch. Annu Rev Med 1970;
21: 67–74.
[90] Nilsson K, Lindell S-E, Schayer RW, Westling H. Metabolism of
(14)C-labelled histamine in pregnant and non-pregnant women.
Clin Sci 1959; 18: 313–9.
[91] Naranjo P. Toxicity of histamine: lethal doses. Handbook of
Experimental Pharmacology. New York: Springer-Verlag, vol 18
(Part 1) 1966: 179–201.
[92] Mense S, Schmidt RF. Activation of group IV afferent units from
muscle by algesic agents. Brain Res 1974; 72: 305–10.
[93] Mense S. Neurophysiological basis of pain in the musculature and
possibilities of their effect. Verh Dtsch Ges Rheumatol 1981; 7:
36–44.
[94] Enestrom S, Bengtsson A, Frodin T. Dermal IgG deposits and increase
of mast cells in patients with fi bromyalgia-relevant fi ndings
or epiphenomena? Scand J Rheumatol 1997; 26: 308–13.
[95] Sann H, Pierau FK. Efferent functions of C-fi ber nociceptors. Z
Rheumatol 1998; 57 Suppl 2: 8–13.
[96] Gibson SJ, Littlejohn GO, Gorman MM, Helme RD, Granges G.
Altered heat pain thresholds and cerebral event-related potentials
following painful CO2 laser stimulation in subjects with fi bromyalgia
syndrome. Pain 1994; 58: 185–93.
[97] Gordon ML, Lebwohl MG, Phelps RG, Cohen SR, Fleischmajer
R. Eosinophilic fasciitis associated with tryptophan ingestion. A
manifestation of eosinophilia-myalgia syndrome. Arch Dermatol
1991; 127: 217–20.
[98] Harper AE. Amino acids of nutritional importance. Toxicants Occurring
Naturally in Foods. Washington, DC: National Academy
Press, 1973: 130–52.
[99] Brown RR. Tryptophan Metabolism: A Review. L-Tryptophan
Current Prospects in Medicine and Drug Safety. Berlin: de Gruyter,
1994: 17–30.
[100] Anonymous commentary. L-tryptophan-a “natural” sedative? Med
Lett Drugs Ther 1977; 19: 108.
[101] Boman B. L-tryptophan: a rational anti-depressant and a natural
hypnotic? Aust N Z J Psychiatry 1988; 22: 83–97.
[102] Zarcone VP Jr, Berger PA, Brodie KH, Sack R, Barchas JD. The
indoleamine hypothesis of depression: an overview and pilot
study. Dis Nerv Syst 1977; 38: 646–53.
[103] Kanof PD, Greengard P. Brain histamine receptors as targets for
antidepressant drugs. Nature 1978; 272: 329–33.
[104] Geracioti TD, Loosen PT, Ekhator NN, Schmidt D, Chambliss B,
Baker DG et al. Uncoupling of serotonergic and noradrenergic
systems in depression: preliminary evidence from continuous
cerebrospinal fl uid sampling. Depress Anxiety 1997; 6: 89–94.
[105] Sirek A, Sirek OV. Serotonin: a review. Can Med Assoc J 1970;
102: 846–9.
[106] Coppen A, Wood K. Tryptophan and depressive illness: confl icting
biochemical and therapeutic issues. Adv Biol Psychiat 1983; 10:
19–29.
[107] Lambert GW, Kaye DM, Cox HS, Vaz M, Turner AG, Jennings GL
et al. Regional 5-hydroxyindoleacetic acid production in humans.
Life Sci 1995; 57: 255–67.
[108] Curzon G. Effects of adrenal hormones and stress on brain serotonin.
Am J Clin Nutr 1971; 24: 830–4.
[109] Sjoerdsma A, Lovenberg W, Engelman K, Carpenter WT, Wyatt
RJ, Gessa GL. Serotonin now: clinical implications of inhibiting
its synthesis with para-chlorophenylalanine. Ann Intern Med
1970; 73: 607–30.
[110] Cryer PE. The carcinoid syndrome. Cecil Textbook of Medicine.
Philedelphia, PA: W. B. Saunders, 1990: 1394–5.
[111] Curtius HC, Farner H, Rey F. In vivo studies of the tryptophan-
5-hydroxylase system. Quantitation of serotonin and tryptamine
using gas chromatography-mass fragmentography. J Chromatogr
1980; 199: 171–9.
[112] Erspamer V. Pharmacology of indolealkylamines. Pharmacol Rev
1954; 6: 425–87.
[113] Thomas DP, Vane JR. 5-hydroxytryptamine in the circulation of
the dog. Nature 1967; 216: 335–8.
[114] Wetterqvist H. Histamine metabolism and excretion. Handbook of
Experimental Pharmacology. New York: Springer-Verlag, vol 18
(Part 2) 1978: 131–50.
[115] Paria BC, Das N, Das SK, Zhao X, Dileepan KN, Dey SK. Histidine
decarboxylase gene in the mouse uterus is regulated by progesterone
and correlates with uterine differentiation for blastocyst
implantation. Endocrinology 1998; 139: 3958–66.
[116] Yamakami J, Sakurai E, Kuramasu A, Sakurai E, Yanai K, Watanabe
T et al. L-Histidine decarboxylase protein and activity in rat brain
microvascular endothelial cells. Infl amm Res 2000; 49: 231–5.
[117] Levine RJ, Sato TL, Sjoerdsma A. Inhibition of histamine synthesis
in the rat by alpha-hydrazino analog of histidine and 4-
bromo-3-hydroxybenzyloxyamine. Biochem Pharmacol 1965; 14:
139–49.
[118] Taylor SL, Hefl e SL. Allergylike intoxications from foods. Food
Hypersensitivity and Adverse Reactions. New York: Marcel
Dekker, 1999: 141–53.
[119] Demis DJ. The mastocytosis syndrome: clinical and biological
studies. Ann Intern Med 1963; 59: 194–206.
[120] Escribano L, Akin C, Castells M, Orfao A, Metcalfe DD. Mastocytosis:
current concepts in diagnosis and treatment. Ann Hematol
2002; 81: 677–90.
[121] Lewkonia RM. Myalgia and eosinophilia associated with ingestion
of tryptophan. An intriguing new syndrome. Arch Intern Med
1990; 150: 2005–7.
[122] Swygert LA, Back EE, Auerbach SB, Sewell LE, Falk H. Eosinophilia-
myalgia syndrome: mortality data from the US national
surveillance system. J Rheumatol 1993; 20: 1711–7.
[123] Robinson-White A, Beaven MA. Presence of histamine and histamine-
metabolizing enzyme in rat and guinea-pig microvascular
endothelial cells. J Pharmacol Exp Ther 1982; 223: 440–5.
[124] Lindell SE, Westling H. Histamine metabolism in man. Handbook
of Experimental Pharmacology. New York: Springer-Verlag, vol 18
(Part 1) 1966: 734–88.
[125] Schayer RW. Catabolism of physiological quantities of histamine
in vivo. Physiol Rev 1959; 39: 116–26.
[126] Buffoni F. Semicarbazide-sensitive amine oxidases: some biochemical
properties and general considerations. Prog Brain Res
1995; 106: 323–31.
[127] Callingham BA, Crosbie AE, Rous BA. Some aspects of the
pathophysiology of semicarbazide-sensitive amine oxidase enzymes.
Prog Brain Res 1995; 106: 305–21.
[128] Callingham BA, Holt A, Elliott J. Properties and functions of
the semicarbazide-sensitive amine oxidases. Biochem Soc Trans
1991; 19: 228–33.
[129] McEwen CM. Human plasma monoamine oxidase. 1. Purifi cation
and identifi cation. J Biol Chem 1965; 240: 2003–10.
[130] Tryding N, Nilsson SE, Tufvesson G, Berg R, Carlstrom S, Elmfors
B et al. Physiological and pathological infl uences on serum
monoamine oxidase level: effect of age, sex, contraceptive steroids
and diabetes mellitus. Scand J Clin Lab Invest 1969; 23: 79–84.
[131] McEwen CM. The soluble monoamine oxidase of human plasma
and sera. Adv Biochem Psychopharmacol 1972; 5.
[132] Bond PA, Cundall RL. Properties of monoamine oxidase (MAO)
in human blood platelets, plasma, lymphocytes and granulocytes.
Clin Chim Acta 1977; 80: 317–26.
[133] Hayes BE, Ostrow PT, Clarke DE. Benzylamine oxidase in normal
and atherosclerotic human aortae. Exp Mol Pathol 1983; 38:
243–54.
[134] Precious E, Lyles GA. Properties of a semicarbazide-sensitive
amine oxidase in human umbilical artery. J Pharm Pharmacol
1988; 40: 627–33.
[135] Buffoni F. Histaminase and related amine oxidases. Pharmacol
Rev 1966; 18: 1163–99.
[136] Elliott J, Callingham BA, Sharman DF. Semicarbazide-sensitive
amine oxidase (SSAO) of the rat aorta. Interactions with some
naturally occurring amines and their structural analogues. Biochem
Pharmacol 1989; 38: 1507–15.
[137] Lyles GA. Properties of mammalian tissue-bound semicarbazidesensitive
amine oxidase: possible clues to its physiological function?
J Neural Transm Suppl 1994; 41: 387–96.
[138] Lyles GA. Mammalian plasma and tissue-bound semicarbazidesensitive
amine oxidases: biochemical, pharmacological and
toxicological aspects. Int J Biochem Cell Biol 1996; 28: 259–74.
[139] Finazzi-Agro A, Floris G, Fadda MB, Crifo C. Inhibition of diamine
oxidase by antihistaminic agents and related drugs. Agents
Actions 1979; 9: 244–7.
[140] Medda R, Padiglia A, Finazzi Agro A, Pedersen JZ, Lorrai A,
Floris G. Tryptamine as substrate and inhibitor of lentil seedling
copper amine oxidase. Eur J Biochem 1997; 250: 377–82.
[141] Rauch N, Rauch RJ. Isozymes of amine oxidase in human plasma
and other tissues. Experientia 1973; 29: 215–7.
[142] Sullivan JP, McDonnell L, Hardiman OM, Farrell MA, Phillips
JP, Tipton KF. The oxidation of tryptamine by the two forms of
monoamine oxidase in human tissues. Biochem Pharmacol 1986;
35: 3255–60.
[143] Robinson DS, Lovenberg W, Keiser H, Sjoerdsma A. Effects of
drugs on human blood platelet and plasma amine oxidase activity
in vitro and in vivo. Biochem Pharmacol 1968; 17: 109–19.
[144] Lin AWSM, Castell DO. Multiple forms of monoamine oxidase in
human plasma. Biochem Med 1975; 13: 141–56.
[145] Brown DD, Tomchick R, Axelrod J. The distribution and properties
of a histamine-methylating enzyme. J Biol Chem 1959; 234:
2948–50.
[146] Snyder SH, Axelrod J. Inhibition of histamine methylation in vivo
by drugs. Biochem Pharmacol 1964; 13: 536–7.
[147] Merril CR, Snyder SH, Bradley DF. Inhibition of histamine
methyltransferase by serotonin and chlorpromazine derivatives:
electronic aspects. Biochim Biophys Acta 1966; 118: 316–24.
[148] Fuhr N, Kownatzki E. Inhibition of rat kidney histamine-Nmethyltransferase
by biogenic amines. Pharmacology 1986; 32:
114–20.
[149] Tachibana T, Taniguchi S, Fujiwara M, Imamura S. Regulation
of the activity of histamine-N-methyltransferase from guinea pig
skin by biogenic amines. Exp Mol Pathol 1986; 45: 257–69.
[150] Taniguchi S, Tachibana T, Miwa S, Fujiwara M, Imamura S. Biogenic
amines in the Arthus reaction. Exp Mol Pathol 1987; 47:
185–92.
[151] Snyder SH, Axelrod J. Tissue metabolism of histamine-C(14) in
vivo. Fed Proc 1965; 24: 774–6.
[152] Axelrod J. Histamine-N-methyltransferase (pig liver). Meth Enzymol
1971; 17 (Part B): 766–9.
[153] Sellinger OZ, Schatz RA, Ohlsson WG. Rat and mouse brain
histamine-N-methyltransferase: modulation by methylated indoleamines.
J Neurochem 1978; 30: 437–45.
[154] Taylor SL, Lieber ER. In vitro inhibition of rat intestinal histaminemetabolizing
enzymes. Food Cosmet Toxicol 1979; 17: 237–40.
[155] Green JP, Prell GD, Khandelwal JK, Blandina P. Aspects of histamine
metabolism. Agents Actions 1987; 22: 1–15.
[156] Zeiger RS, Yurdin DL, Colten HR. Histamine metabolism. II. Cellular
and subcellular localization of the catabolic enzymes, histaminase
and histamine methyl transferase, in human leukocytes. J
Allergy Clin Immunol 1976; 58: 172–9.
[157] Herman JJ, Rosner IK, Davis AE 3d, Zeiger RS, Arnaout MA,
Colten HR. Complement-dependent histaminase release from human
granulocytes. J Clin Invest 1979; 63: 1195–202.
[158] Houen G. Mammalian Cu-containing amine oxidases (CAOs):
new methods of analysis, structural relationships, and possible
functions. APMIS Suppl 1999; 96: 1–46.
[159] Haddock RC, Mack P, Fogerty FJ, Baenziger NL. Role of receptors
in metabolic interaction of histamine with human vascular
endothelial cells and skin fi broblasts. An ordered sequence of
enzyme action. J Biol Chem 1987; 262: 10220–8.
[160] Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J,
Leder P, Luster AD. Human eotaxin is a specifi c chemoattractant
for eosinophil cells and provides a new mechanism to explain tissue
eosinophilia. Nat Med 1996; 2: 449–56.
[161] Kovacs A. Antihistaminic activity of eosinophil leukocytes. Experientia
1950; 6: 349–50.
[162] Broome J, Archer RK. Effect of equine eosinophils on histamine
in vitro. Nature 1962; 193: 446–8.
[163] Rosen LA, Hollis TM, Sharma MG. Alterations in bovine endothelial
histidine decarboxylase activity following exposure to
shearing stresses. Exp Mol Pathol 1974; 20: 329–43.
[164] Smith SA. Persistent microvasculopathy in chronic eosinophiliamyalgia
syndrome. Adv Exp Med Biol 1996; 398: 359–64.
[165] LeRoy EC. Pathogenesis of scleroderma (systemic sclerosis). J
Invest Dermatol 1982; 79 Suppl 1: 87s–9s.
[166] Claman HN, Giorno RC, Seibold JR. Endothelial and fi broblastic
activation in scleroderma. The myth of the “uninvolved skin”.
Arthritis Rheum 1991; 34: 1495–501.
[167] Anderson GH, Brosnan J, Hoffer J, Johnston J, Leiter L, Pandey
GS et al. Report of the Expert Advisory Committee on Amino
Acids. Ottawa: Health and Welfare Canada, Minister of Supply
and Services Canada, 1990: 1–52.
[168] Herbert V. L-Tryptophan A medicolegal case against over-thecounter
marketing of supplements of amino acids. Nutr Today
1992; 27: 27–30.
[169] Eidson M, Philen RM, Sewell CM, Voorhees R, Kilbourne EM. Ltryptophan
and eosinophilia-myalgia syndrome in New Mexico.
Lancet 1990; 335: 645–8.
[170] Patmas MA. Eosinophilia-myalgia syndrome not associated with
L-tryptophan. NJ Med 1992; 89: 285–6.
[171] Clauw DJ, Flockhart DA, Mullins W, Katz P, Medsger TA Jr.
Eosinophilia-myalgia syndrome not associated with the ingestion
of nutritional supplements. J Rheumatol 1994; 21: 2385–7.
[172] Elliott J, Callingham BA, Sharman DF. Semicarbazide-sensitive
amine oxidase (SSAO) of the rat aorta. Interactions with some
naturally occurring amines and their structural analogues. Biochem
Pharmacol 1989; 38: 1507–15.
[173] Arunlakshana O, Mongar JL, Schild HO. Potentiation of pharmacological
effects of histamine by histaminase inhibitors. J Physiol
1954; 123: 32–54.
[174] Hui JY, Taylor SL. Inhibition of in vivo histamine metabolism
in rats by foodborne and pharmacologic inhibitors of diamine
oxidase, histamine-N-methyltransferase, and monoamine oxidase.
Toxicol Appl Pharmacol 1985; 81: 241–9.
[175] Slutsker L, Hoesly FC, Miller L, Williams LP, Watson JC, Fleming
DW. Eosinophilia-myalgia syndrome associated with exposure
to tryptophan from a single manufacturer. JAMA 1990; 264:
213–7.
[176] Montenero AS. Toxicity and tolerance of tryptophan and its metabolites.
Acta Vitaminol Enzymol 1978; 32: 188–94.
[177] During MJ, Freese A. Is L-tryptophan safe? Aust N Z J Psychiatry
1988; 22: 339.
[178] Freese A, Schwartz KJ, During M. Potential neurotoxicity of tryptophan.
Ann Intern Med 1988; 108: 312–3.
[179] Tsuchiya H, Hayashi T, Tatsumi M, Hoshino Y, Ohtani S, Takagi
N. High-performance liquid-chromatographic analysis for serotonin
and tryptamine excreted in urine after oral loading with
L-tryptophan. Clin Chem 1989; 35: 43–7.
[180] Ad Hoc Expert Panel. Safety of Amino Acids Used as Dietary
Supplements. Bethesda, MD : Life Sciences Research Offi ce,
FASEB, July, 1992: vii, 18–22, 34, 91–110.
[181] Mannaioni PF, Ledda F, Baldi V, Catini C. Differential release of
histamine by 5-hydroxy-tryptamine, noradrenaline and reserpine
from neoplastic mast cells in vitro: biological and fl uorescence
microscope observations. Eur J Pharmacol 1968; 3: 203–11.
[182] Levine RJ. Histamine synthesis in man: inhibition by 4-bromo-3-
hydroxybenzyloxyamine. Science 1966; 154: 1017–9.
[183] Erdmann R, Jones M. The Amino Revolution. New York: Simon
& Schuster, 1987: 1–248.
[184] Bender DA. Biochemistry of tryptophan in health and disease.
Mol Aspects Med 1982; 6: 101–97.
[185] Hayaishi O. My life with tryptophan-Never a dull moment.
Advances in Tryptophan Research 1992. Toyoake, Japan: Fujita
Health University Press, 1992: 3–16.
[186] Curzon G, Knott PJ. Environmental, toxicological, and related
aspects of tryptophan metabolism with particular reference to
the central nervous system. CRC Crit Rev Toxicol 1977; 5:
145–87.
[187] Heinzow B, Ellrott T. Formic acid in urine-a signifi cant parameter
in environmental diagnosis? Zentralbl Hyg Umweltmed 1992;
192: 455–61.
[188] Chance B. On the reaction of catalase peroxides with acceptors. J
Biol Chem 1950; 182: 649–58.
[189] Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121–6.
[190] Cline MJ. Metabolism of the circulating leukocyte. Physiol Rev
1965; 45: 674–720.
[191] Dechatelet LR, Migler RA, Shirley PS, Bass DA, McCall CE.
Enzymes of oxidative metabolism in the human eosinophil. Proc
Soc Exp Biol Med 1978; 158: 537–41.
[192] Iyer GYN, Islam MF, Quastel JH. Biochemical aspects of phagocytosis.
Nature 1961; 192: 535–41.
[193] Mickenberg ID, Root RK, Wolff SM. Bactericidal and metabolic
properties of human eosinophils. Blood 1972; 39: 67–80.
[194] Briggs RT, Drath DB, Karnovsky ML, Karnovsky MJ. Localization
of NADH oxidase on the surface of human polymorphonuclear
leukocytes by a new cytochemical method. J Cell Biol 1975;
67: 566–86.
[195] DeChatelet LR, Shirley PS. Pyridine nucleotide-dependent generation
of hydrogen peroxide by a particulate fraction from human
neutrophils. J Immunol 1981; 126: 1165–9.
[196] Green TR, Pratt KL. A reassessment of the product specifi city of
the NADPH:O2 oxidoreductase of human neutrophils. Biochem
Biophys Res Commun 1987; 142: 213–20.
[197] Williams-Smith DL, Payne LN, Wyard SJ. Catalase depression in
malignant liver from chickens with myeloblastosis and Marek’s
disease. Br J Cancer 1984; 50: 399–405.
[198] Payne LN, Rennie M. Sequential changes in the numbers of B
and T lymphocytes and other leukocytes in the blood in Marek’s
disease. Int J Cancer 1976; 18: 510–20.
[199] Agner K, Theorell H. On the mechanism of the catalase inhibition
by anions. Arch Biochem 1946; 10: 321–38.
[200] Chatterjee U, Kumar A, Sanwal GG. Purifi cation and properties
of goat liver catalase: two pH optima. Indian J Biochem Biophys
1989; 26: 140–7.
[201] Smith AM, Morrison WL, Milham PJ. Oxidation of indole-3-acetic
acid by peroxidase: involvement of reduced peroxidase and
compound III with superoxide as a product. Biochemistry 1982;
21: 4414–9.
[202] Paradis MR, Breeze RG, Bayly WM, Counts DF, Laegreid WW.
Acute hemolytic anemia after oral administration of L-tryptophan
in ponies. Am J Vet Res 1991; 52: 742–7.
[203] De Landsheere BC. Effect of beta indolyl-acetic acid and beta
indolyl butyric acid on leucocyte distribution in the guinea pig.
Arch Int Pharmacodyn 1958; 114: 156–61.
[204] Stachów A,Jablonska S,Kencka D. Tryptophan metabolism in
scleroderma and eosinophilic fasciitis. Systemic Sclerosis (Scleroderma).
New York: Gower Medical Publishing, 1985: 130–4.
[205] Anonymous commentary. Toxic Oil Syndrome and Eosinophilia-
Myalgia Syndrome: Clinical Aspects. WHO Regional Offi ce for
Europe, Copenhagen: EUR/HFA target 22, 1993: 1–18.
[206] Caspi D, Fishel R, Varon M, Yona E, Baratz M, Yaron M. Multisystem
presentation of eosinophilic fasciitis. Rheumatol Rehabil
1982; 21: 218–21.
[207] Golitz LE. Fasciitis with eosinophilia: The Shulman syndrome.
Int J Dermatol 1980; 19: 552–5.
[208] Hamilton ME. Eosinophilic fasciitis associated with L-tryptophan
ingestion. Ann Rheum Dis 1991; 50: 55–6.
[209] Jablonska S, Sieminska S. Eosinophilic fasciitis. Przegl Dermatol
1982; 69: 121–6.
[210] DiMauro S, Miranda AF, Hays AP, Franck WA, Hoffman GS,
Schoenfeldt RS et al. Myoadenylate deaminase defi ciency-muscle
biopsy and muscle culture in a patient with gout. J Neurol Sci
1980; 47: 191–202.
[211] Murali MR. Exercise-induced anaphylaxis. Food Hypersensitivity
and Adverse Reactions. New York: Marcel Dekker, 1999:
321–9.
[212] Schule C, Baghai T, Zwanzger P, Ella R, Eser D, Padberg F et al.
Attenuation of hypothalamic-pituitary-adrenocortical hyperactivity
in depressed patients by mirtazapine. Psychopharmacology
(Berl) 2003; 166: 271–5.
[213] Badawy AA, Morgan CJ. Effects of acute paroxetine administration
on tryptophan metabolism and disposition in the rat. Br J
Pharmacol 1991; 102: 429–33.
[214] File SE. Interactions of anxiolytic and antidepressant drugs with
hormones of the hypothalamic-pituitary-adrenal axis. Pharmacol
Ther 1990; 46: 357–75.
[215] Hanley NR, Van de Kar LD. Serotonin and the neuroendocrine
regulation of the hypothalamic-pituitary-adrenal axis in health
and disease. Vitam Horm 2003; 66: 189–255.
[216] Sala GB, Hayashi K, Catt KJ, Dufau ML. Adrenocorticotropin action
in isolated adrenal cells. The intermediate role of cyclic AMP
in stimulation of corticosterone synthesis. J Biol Chem 1979; 254:
3861–5.
[217] Papadopoulos V, Nowzari FB, Krueger KE. Hormone-stimulated
steroidogenesis is coupled to mitochondrial benzodiazepine receptors.
Tropic hormone action on steroid biosynthesis is inhibited
by fl unitrazepam. J Biol Chem 1991; 266: 3682–7.
[218] Timonen M, Jokelainen J, Silvennoinen-Kassinen S, Herva A,
Zitting P, Xu B et al. Association between skin test diagnosed
atopy and professionally diagnosed depression: a Northern
Finland 1966 Birth Cohort study. Biol Psychiatry 2002; 52:
349–55.
[219] Curzon G. Tryptophan pyrrolase – a biochemical factor in depressive
illness? Br J Psychiatry 1969; 115: 1367–74.
[220] Lapin IP, Oxenkrug GF. Intensifi cation of the central serotoninergic
processes as a possible determinant of the thymoleptic effect.
Lancet 1969; 1: 132–6.
[221] Curzon G. Serotonergic mechanisms of depression. Clin Neuropharmacol
1988; 11 Suppl 2: S11–20.
[222] Altman K, Greengard O. Correlation of kynurenine excretion with
liver tryptophan pyrrolase levels in disease and after hydrocortisone
induction. J Clin Invest 1966; 45: 1527–34.
[223] Greengard O. Relationship between urinary excretion of kynurenine
and liver tryptophan oxygenase activity. Am J Clin Nutr
1971; 24: 709–11.
[224] Knox WE, Auerbach VH. The hormonal control of tryptophan
peroxidase in the rat. J Biol Chem 1955; 214: 307–13.
[225] Ebadi M, Gessert CF, Al-Sayegh A. Drug-pyridoxal phosphate
interactions. Q Rev Drug Metab Drug Interact 1982; 4: 289–
331.
[226] Chytil F. Activation of liver tryptophan oxygenase by adenosine
3’,5’-phosphate and by other purine derivatives. J Biol Chem
1968; 243: 893–9.
[227] Cho-Chung YS, Pitot HC. Feedback control of rat liver tryptophan
pyrrolase. I. End product inhibition of trytophan pyrrolase activity.
J Biol Chem 1967; 242: 1192–8.
[228] Knox WE. Two mechanisms which increase in vivo the liver tryptophan
peroxidase activity: specifi c enzyme adaptation and stimulation
of the pituitary-adrenal system. Br J Exptl Pathol 1951; 32:
462–9.
[229] Civen M, Knox WE. The independence of hydrocortisone and
tryptophan inductions of tryptophan pyrrolase. J Biol Chem 1959;
234: 1787–90.
[230] Knox WE. The regulation of tryptophan pyrrolase activity by
tryptophan. Adv Enzyme Regul 1966; 4: 287–97.
[231] Fischl J, Rabiah S. Determination of free and total indole-3-acetic
acid and of the indole index. Clin Chem 1964; 10: 281–90.
[232] Frey PA, Moss M, Petrovich R, Baraniak J. The roles of S-adenosylmethionine
and pyridoxal phosphate in the lysine 2,3-aminomutase
reaction. Ann NY Acad Sci 1990; 585: 368–78.
[233] György P. Developments leading to the metabolic role of vitamin
B6. Am J Clin Nutr 1971; 24: 1250–6.
[234] Wolf H. Studies on tryptophan metabolism in man. Scand J Clin
Lab Invest 1974; 33: 1–186.
[235] Houpt JB, Ogryzlo MA, Hunt M. Tryptophan metabolism in man
(with special reference to rheumatoid arthritis and scleroderma).
Semin Arthritis Rheum 1973; 2: 333–53.
[236] Hamfelt A. Enzymatic determination of pyridoxal phosphate in
plasma by decarboxylation of L-tyrosine-14 C (U) and a comparison
with the tryptophan load test. Scand J Clin Lab Invest 1967;
20: 1–10.
[237] Hamfelt A, Wetterberg L. Neuropathy in porphyria. Lancet 1968;
1: 50.
[238] Ogasawara N, Hagino Y, Kotake Y. Kynurenine-transaminase,
kynureninase and the increase of xanthurenic acid excretion. J
Biochem (Tokyo) 1962; 52: 162–6.
[239] Hoes MJ. Biological markers in psychiatry. Acta Psychiatr Belg
1986; 86: 220–41.
[240] Hoes MJ, Sijben N. The clinical signifi cance of disordered renal
excretion of xanthurenic acid in depressive patients. Psychopharmacology
(Berl) 1981; 75: 346–9.
[241] Young SN, Sourkes TL. Antidepressant action of tryptophan.
Lancet 1974; 2: 897–8.
[242] Coon WW. The tryptophan load and pyridoxine defi ciency. Am J
Clin Pathol 1966; 46: 345–8.
[243] Hughes PA, Raine DN. In vivo formation of pyridoxal phosphate
Schiff’s base – an inherent defect in the tryptophan load test. Clin
Chim Acta 1966; 14: 399–402.
[244] Rose DP. The infl uence of oestrogens on tryptophan metabolism
in man. Clin Sci 1966; 31: 265–72.
[245] Coursin DB. Central nervous system hypersensitivity to tryptophan.
Am J Clin Nutr 1971; 24: 821–5.
[246] Green AR, Aronson JK. Metabolism of an oral tryptophan load
III: effect of a pyridoxine supplement. Br J Clin Pharmacol 1980;
10: 617–9.
[247] Sourkes TL. Toxicology of serotonin precursors. Adv Biol Psychiat
1983; 10: 160–75.
[248] Takeuchi F, Shibata Y. Kynurenine metabolism in vitamin-B-6-
defi cient rat liver after tryptophan injection. Biochem J 1984; 220:
693–9.
[249] Schaeffer MC. Detrimental effects of repeated administration of
the tryptophan-load test for vitamin B6 status on defi cient and
pair-fed rats. Nutr Res 1988; 8: 1307–8.
[250] Allegri G, Costa C, Baccichetti F, Biasiolo M. Effects of two different
loading doses of L-tryptophan on the urinary excretion of
tryptophan metabolites in rats, mice and guinea pigs. Correlation
with the enzyme activities. Ital J Biochem 1987; 36: 194–203.
[251] Sternberg EM, Van Woert MH, Young SN, Magnussen I, Baker H,
Gauthier S et al. Development of a scleroderma-like illness during
therapy with L-5-hydroxytryptophan and carbidopa. N Engl J
Med 1980; 303: 782–7.
[252] Mainetti C, Fathi M, Saurat JH. L-tryptophan-induced eosinophiliamyalgia
syndrome. II. Partial correction of abnormal tryptophan
metabolism by pyridoxine. Dermatologica 1991; 183: 62–5.
[253] Hisatomi A, Kubota A, Ohashi M, Umeda F, Nawata H, Imamura
T et al. Elevated L-kynurenine level and its normalization by
prednisolone in a patient with eosinophilia-myalgia syndrome.
Fukuoka Igaku Zasshi 1997; 88: 11–7.
[254] Brown RR, Fissette PL, Arend RA, Ozaki Y. Tryptophan metabolism
and immune markers in eosinophilia-myalgia syndrome
associated with tryptophan ingestion. Advances in Tryptophan
Research 1992. Toyoake, Japan: Fujita Health University Press,
1992: 337–46.
[255] Rudzite VK. The effect of tryptophan, serotonin, kynurenine,
corticosteroids and peroxidases on the activity of tryptophan pyrrolase,
the decarboxylase of 5-OH tryptophan and liver catalase in
rats. Biull Eksp Biol Med 1969; 67: 48–50.
[256] Paul KG, Kumlien A, Brody S. Studies on eosinophil granulocytes.
II. The effect of cytostatics on the uterine response to
oestrogen. Experientia 1966; 22: 799–800.
[257] Loo G, Smith JT. Effect of pyridoxine defi ciency on phospholipid
methylation in rat liver microsomes. Lipids 1986; 21: 409–12.
[258] Baudry M, Chast F, Schwartz JC. Studies on S-adenosylhomocysteine
inhibition of histamine transmethylation in brain. J Neurochem
1973; 20: 13–21.
[259] Mueller JF, Vilter RW. Pyridoxine defi ciency in human beings
induced with desoxypyridoxine. J Clin Invest 1950; 29: 193–201.
[260] Vilter RW, Mueller JF, Glazer HS, Jarrold T, Abraham J, Thompson
C et al. The effect of vitamin B6 defi ciency induced by desoxypyridoxine
in human beings. J Lab Clin Med 1953; 42: 335–57.
[261] Brown RR. Possible role for vitamin B6 in cancer prevention and
treatment. Clinical and Physiological Applications of Vitamin B6.
New York: Alan R. Liss, 1988: 279–301.
[262] Anonymous commentary. Pyridoxine Hydrochloride. The United
States Dispensatory. Philadelphia: Lippincott, 1967: 974.
[263] Cantor MM, Scott JW. Agranulocytic angina effectively treated
with intravenous pyridoxine (vitamin B6). Can Med Assoc J
1945; 52: 368–71.
[264] Daniels SR, Hudson JI, Horwitz RI. Epidemiology of potential
association between L-tryptophan ingestion and eosinophilia-myalgia
syndrome. J Clin Epidemiol 1995; 48: 1413–27; discussion
1429–40.
[265] Kamb ML, Murphy JJ, Jones JL, Caston JC, Nederlof K, Horney
LF et al. Eosinophilia-myalgia syndrome in L-tryptophan-exposed
patients. JAMA 1992; 267: 77–82.
[266] Rao KS, Menon PK, Hilman BC, Sebastian CS, Bairnsfather L.
Duration of the suppressive effect of tricyclic antidepressants on
histamine-induced wheal-and-fl are reactions in human skin. J Allergy
Clin Immunol 1988; 82: 752–7.
[267] Pletscher A. The discovery of antidepressants: a winding path.
Experientia 1991; 47: 4–8.
[268] Green JP, Maayani S. Tricyclic antidepressant drugs block histamine
H2 receptor in brain. Nature 1977; 269: 163–5.
[269] Bakish D, Lapierre YD. Myalgia with the new generation antidepressants.
J Clin Psychopharmacol 1986; 6: 195–6.
[270] Weiner RI, Ganong WF. Role of brain monoamines and histamine
in regulation of anterior pituitary secretion. Physiol Rev 1978; 58:
905–76.
[271] Hill SJ. Distribution, properties, and functional characteristics
of three classes of histamine receptor. Pharmacol Rev 1990; 42:
45–83.
[272] Reilly MA, Sigg EB. Suppression of histamine-induced adrenocorticotropic
hormone release by antihistamines and antidepressants.
J Pharmacol Exp Ther 1982; 222: 583–8.
[273] Feighner JP. Mechanism of action of antidepressant medications.
J Clin Psychiatry 1999; 60 Suppl 4: 4–11; discussion 12–3.
[274] Ito C, Shen H, Toyota H, Kubota Y, Sakurai E, Watanabe T et al.
Effects of the acute and chronic restraint stresses on the central
histaminergic neuron system of Fischer rat. Neurosci Lett 1999;
262: 143–5.
[275] Nomura J. Effects of stress and psychotropic drugs on rat liver
tryptophan pyrrolase. Endocrinology 1965; 76: 1190–4.
[276] Badawy AA, Evans M. Inhibition of rat liver tryptophan pyrrolase
activity and elevation of brain tryptophan concentration by acute
administration of small doses of antidepressants. Br J Pharmacol
1982; 77: 59–67.
[277] Knox WE, Mehler AH. The adaptive increase of the tryptophan
peroxidase-oxidase system of liver. Science 1951; 113: 237–8.
[278] Denckla WD, Dewey HK. Tryptamine toxicity in adrenalectomized
rats; its prevention with tryptamine and hydrocortisone. J
Pharmacol Exp Ther 1967; 158: 128–34.
[279] Carlsten A. Effect of adrenalectomy on lymph and plasma histamine.
Acta Physiol Scand (Suppl 70) 1950; 20: 33–46.
[280] Roberts F, Calcutt CR. Histamine and the hypothalamus. Neuroscience
1983; 9: 721–39.
[281] Haeger K, Kahlson G. Disappearance of histaminase from the
whole body following adrenalectomy in cats. Acta Physiol Scand
1952; 25: 255–8.
[282] Carlsten A. On the sources of the histamine present in thoracic
duct lymph. Acta Physiol Scand (Suppl 70) 1950; 20: 5–26.
[283] Hansson R. Heparin-induced increase of diamine oxidasehistaminase(
EC 1.4.3.6.) in blood and lymph. Scand J Clin Lab
Invest Suppl 1973; 129: 1–23.
[284] Wollin A, Wang X, Tso P. Nutrients regulate diamine oxidase release
from intestinal mucosa. Am J Physiol 1998; 275: R969–75.
[285] Haeger K, Jacobsohn D, Kahlson G. The levels of histaminase
and histamine in the gastrointestinal mucosa and kidney of the
cat deprived of the hypophysis or the adrenal glands. Acta Physiol
Scand 1952; 25: 243–54.
[286] Kahlson G. A place for histamine in normal physiology. Lancet
1960; 1: 67–71.
[287] Nurnberger JI Jr, Berrettini W, Simmons-Alling S, Lawrence D,
Brittain H. Blunted ACTH and cortisol response to afternoon
tryptophan infusion in euthymic bipolar patients. Psychiatry Res
1990; 31: 57–67.
[288] Calogero AE, Gallucci WT, Chrousos GP, Gold PW. Interaction
between GABAergic neurotransmission and rat hypothalamic
corticotropin-releasing hormone secretion in vitro. Brain Res
1988; 463: 28–36.
[289] Kalogeras KT, Calogero AE, Kuribayiashi T, Khan I, Gallucci
WT, Kling MA et al. In vitro and in vivo effects of the triazolobenzodiazepine
alprazolam on hypothalamic-pituitary-adrenal function:
pharmacological and clinical implications. J Clin Endocrinol
Metab 1990; 70: 1462–71.
[290] Oishi R, Nishibori M, Itoh Y, Saeki K. Diazepam-induced decrease
in histamine turnover in mouse brain. Eur J Pharmacol
1986; 124: 337–42.
[291] Thorn GW, Forsham PH, Prunty FTG, Hilla AG. A test for adrenal
cortical insuffi ciency. JAMA 1948; 137: 1005–9.
[292] Speirs RS. Assay of ACTH activity based on the eosinopenic
response in normal and hypophysectomized mice. Endocrinology
1953; 52: 300–10.
[293] Maslinski C. Histamine and its metabolism in mammals. Part II:
Catabolism of histamine and histamine liberation. Agents Actions
1975; 5: 183–225.
[294] Spencer PS, West GB. Thyroid-adrenocortical antagonism and
histamine metabolism. Nature 1963; 199: 1298–9.
[295] Okudaira H, Mori A. Simple understanding and optimistic strategy
for coping with atopic diseases. IL-5 central hypothesis on eosinophilic
infl ammation. Int Arch Allergy Immunol 1998; 117: 11–9.
[296] Cohen SG. Immunologic aspects of eosinophilia. N Engl Reg Allergy
Proc 1985; 6: 352–9.
[297] Meagher LC, Cousin JM, Seckl JR, Haslett C. Opposing effects
of glucocorticoids on the rate of apoptosis in neutrophilic and
eosinophilic granulocytes. J Immunol 1996; 156: 4422–8.
[298] Schayer RW. A unifi ed theory of glucocorticoid action. Perspect
Biol Med 1964; 8: 71–84.
[299] Hertzman PA, Clauw DJ, Kaufman LD, Varga J, Silver RM,
Thacker HL et al. The eosinophilia-myalgia syndrome: status
of 205 patients and results of treatment 2 years after onset. Ann
Intern Med 1995; 122: 851–5.
[300] Connolly SM, Quimby SR, Griffi ng WL, Winkelmann RK.
Scleroderma and L-tryptophan: a possible explanation of the
eosinophilia-myalgia syndrome. J Am Acad Dermatol 1990; 23:
451–7.
[301] Gillis CN. Peripheral metabolism of serotonin. Serotonin and the
Cardiovascular System. New York: Raven Press, 1985: 27–36.
[302] Schild HO. The multiple facets of histamine research. Agents Actions
1981; 11: 12–9.
[303] Shapiro S. L-tryptophan and eosinophilia-myalgia syndrome.
Lancet 1994; 344: 817–9.
[304] Hatch DL, Goldman LR. Reduced severity of eosinophilia-myalgia
syndrome associated with the consumption of vitamin-containing
supplements before illness. Arch Intern Med 1993; 153:
2368–73.
[305] Yukawa T, Kroegel C, Chanez P, Dent G, Ukena D, Chung KF et
al. Effect of theophylline and adenosine on eosinophil function.
Am Rev Respir Dis 1989; 140: 327–33.
[306] Reed CE, Cohen M, Enta T. Reduced effect of epinephrine on circulating
eosinophils in asthma and after beta-adrenergic blockade
or Bordetella pertussis vaccine. With a note on eosinopenia after
methacholine. J Allergy 1970; 46: 90–102.
[307] Venge P, Dahl R. The eosinophil and intrinsic asthma. Agents Actions
Suppl 1989; 28: 67–74.
[308] Varga J, Maul GG, Jimenez SA. Autoantibodies to nuclear lamin
C in the eosinophilia-myalgia syndrome associated with L-tryptophan
ingestion. Arthritis Rheum 1992; 35: 106–9.
[309] Klein R, Berg PA. A comparative study on antibodies to nucleoli
and 5-hydroxytryptamine in patients with fi bromyalgia syndrome
and tryptophan-induced eosinophilia-myalgia syndrome. Clin
Investig 1994; 72: 541–9.
[310] Spencer PS, Schaumberg HH, Ludolph AC. Experimental and
Clinical Neurotoxicology. New York: Oxford Univeristy Press,
2000: 1–1310.
[311] Spitzer WO, Haggerty JL, Berkson L, Davis W, Palmer W, Tamblyn
R et al. Continuing occurrence of eosinophilia myalgia syndrome
in Canada. Br J Rheumatol 1995; 34: 246–51.
[312] Spitzer WO, Haggerty JL, Berkson L, Davis W, Palmer W,
Tamblyn R et al. Analysis of Centers for Disease Control and
Prevention criteria for the eosinophilia-myalgia syndrome in a
geographically defi ned population. J Rheumatol Suppl 1996; 46:
73–9; discussion 79–80.
[313] Hudson JI, Pope HG Jr, Daniels SR, Horwitz RI. Eosinophiliamyalgia
syndrome or fi bromyalgia with eosinophilia? JAMA
1993; 269: 3108–9.
[314] Shapiro S. Comment. J Rheumatol Suppl 1996; 23: 89–91.
[315] Shapiro S. L-tryptophan and eosinophilia-myalgia syndrome.
Lancet 1994; 343: 1035–7.
[316] Horwitz RI, Daniels SR. Bias or biology: evaluating the epidemiologic
studies of L-tryptophan and the eosinophilia-myalgia
syndrome. J Rheumatol Suppl 1996; 46: 60–72.
[317] Sanchez-Porro Valades P, Posada de la Paz M, de Andres Copa P,
Gimenez Ribota O, Abaitua Borda I. Toxic oil syndrome: survival
in the whole cohort between 1981 and 1995. J Clin Epidemiol
2003; 56: 701–8.
[318] Sattler J, Lorenz W. Intestinal diamine oxidases and enteralinduced
histaminosis: studies on three prognostic variables in
an epidemiological model. J Neural Transm Suppl 1990; 32:
291–314.
[319] Leape LL, Bates DW, Cullen DJ, Cooper J, Demonaco HJ, Gallivan
T et al. Systems analysis of adverse drug events. ADE Prevention
Study Group. JAMA 1995; 274: 35–43.
[320] Smith MJ, Ryan DE, Nakanishi K, Frank P, Hodgson KO.
Vanadian in ascidians and the chemistry of tunichromes. Metal
Ions in Biological Systems. New York: Marcel Dekker, 1995:
423–90.
[321] Reason J. The contribution of latent human failures to the breakdown
of complex systems. Philos Trans R Soc Lond B Biol Sci
1990; 327: 475–84.
[322] Lewinsohn R. Amine oxidase in human blood vessels and nonvascular
smooth muscle. J Pharm Pharmacol 1981; 33: 569–75.
[323] Bochner BS, Friedman B, Krishnaswami G, Schleimer RP, Lichtenstein
LM, Kroegel C. Episodic eosinophilia-myalgia-like
syndrome in a patient without L-tryptophan use: association with
eosinophil activation and increased serum levels of granulocytemacrophage
colony-stimulating factor. J Allergy Clin Immunol
1991; 88: 629–36.
[324] Roberts HJ. Aspartame, tryptophan, and other amino acids as potentially
hazardous experiments. South Med J 1990; 83: 1110–1.
[325] Garbarg M, Halpern B. The regulation of gastric histidine decarboxylase
activity. I. Effect of pyridoxine defi ciency. Life Sci [II]
1971; 10: 1211–7.
[326] Lewinsohn R. Mammalian monoamine-oxidizing enzymes, with
special reference to benzylamine oxidase in human tissues. Braz J
Med Biol Res 1984; 17: 223–56.
[327] Mondovi B. Structure and Functions of Amine Oxidases. Boca
Raton: CRC Press, 1985: 1–285.
[328] Briggs M, Briggs M. Relationship between monoamine oxidase
activity and sex hormone concentration in human blood plasma. J
Reprod Fertil 1972; 29: 447–50.
[329] Kapeller-Adler R. Amine Oxidases and Methods for their Study.
New York: Johm Wiley & Sons, 1970: 1–307.
[330] Lin AWSM, Davis LM, Castell DO. Isoenzyme composition of
human plasma monoamine oxidase in normal subjects and in
fi brotic liver disease. Proc Soc Exp Biol Med 1976; 151: 40–3.
[331] Hospers JJ, Schouten JP, Weiss ST, Postma DS, Rijcken B. Eosinophilia
is associated with increased all-cause mortality after a
follow-up of 30 years in a general population sample. Epidemiology
2000; 11: 261–8.
[332] Gullino P, Winitz M, Birnbaum SM, Cornfi eld J, Otey MC,
Greenstein JP. Studies on metabolism of amino acids and related
compounds in vivo. I. Toxicity of essential amino acids, individually
and in mixtures, and protective effect of L-arginine. Arch Biochem
1956; 64: 319–32.
[333] Gagne MA, Wollin A, Navert H, Pinard G. Anomaly of histamine
methylation in endogenous depression. Prog Neuropsychopharmacol
Biol Psychiatry 1982; 6: 483–6.
[334] Archer RK. Eosinophil leucocytes and their reactions to histamine
and 5-hydroxytryptamine. J Path Bact 1959; 78: 95–103.
[335] Capelli A, Jasonni V, Piccaluga A. Experimental research on the
behavior of tissue and circulating eosinophils, of enterochromaf-
fi n cells and tryptophan-positive cells during processes of resynthesis
of serotonin. G Clin Med 1967; 48: 274–93.
[336] Stover P, Schirch V. The metabolic role of leucovorin. Trends
[337] Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A
et al. Hyperhomocysteinemia and low pyridoxal phosphate. Common
and independent reversible risk factors for coronary artery
disease. Circulation 1995; 92: 2825–30.
[338] Eloranta TO, Kajander EO, Raina AM. A new method for the assay
of tissue. S-adenosylhomocysteine and S-adenosylmethione.
Effect of pyridoxine defi ciency on the metabolism of S-adenosylhomocysteine,
S-adenosylmethionine and polyamines in rat liver.
Biochem J 1976; 160: 287–94.
[339] McCully KS. Homocysteine, folate, vitamin B6, and cardiovascular
disease. JAMA 1998; 279: 392–3.
[340] Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP,
Riezler R et al. The effect of a subnormal vitamin B-6 status on
homocysteine metabolism. J Clin Invest 1996; 98: 177–84.
[341] Doke S, Inagaki N, Hayakawa T, Tsuge H. Effects of vitamin B6
defi ciency on cytokine levels and lymphocytes in mice. Biosci
Biotechnol Biochem 1998; 62: 1008–10.
[342] Oroszi G, Enoch MA, Chun J, Virkkunen M, Goldman D.
Thr105Ile, a functional polymorphism of histamine-N-methyltransferase,
is associated with alcoholism in two independent
populations. Alcohol Clin Exp Res 2005; 29: 303–9.
[343] Hill SJ. Distribution, properties, and functional characteristics
of three classes of histamine receptor. Pharmacol Rev 1990; 42:
45–83.
[344] Zeller EA. Diamine oxidases. The Enzymes. New York: Academic
Press, 1963: 313–35.
[345] Tatai K. Response of the pituitary-adrenocortical system to mental
strain in healthy women. Jap J Physiol 1951; 1: 316–9.
[346] Gavish M, Bachman I, Shoukrun R, Katz Y, Veenman L, Weisinger
G et al. Enigma of the peripheral benzodiazepine receptor.
Pharmacol Rev 1999; 51: 629–50.
[347] Andersson E. Adrenal cortical function in bronchial asthma and
its diagnostic value. Acta allergol 1953; 6: 107–17.
[348] Timonen M, Jokelainen J, Hakko H, Silvennoinen-Kassinen S,
Meyer-Rochow VB, Herva A et al. Atopy and depression: results
from the Northern Finland 1966 Birth Cohort Study. Mol Psychiatry
2003; 8: 738–44.
[349] Dooley DM,Golnik KC. Spectroscopic and kinetics studies of the
inhibition of pig kidney diamine oxidase by anions. J Biol Chem
1983; 258: 4245–8.
[350] Loft S, Otte J, Poulsen HE, Sorensen H, Srensen H. Infl uence of
intact and myrosinase-treated indolyl glucosinolates on the metabolism
in vivo of metronidazole and antipyrine in the rat. Food
Chem Toxicol 1992; 30: 927–35.
[351] Beare JL, Beaton JR. Effect of rapeseed oil on food intake in the
rat. Can J Physiol Pharmacol 1967; 45: 1093–4.
[352] Stankovich A. Systems analysis and professional knowledge. N
Engl J Med 1968; 278: 395.

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