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5-HT1A dysfunction in borderline personality disorder 总被引:2,自引:0,他引:2
Hansenne M Pitchot W Pinto E Reggers J Scantamburlo G Fuchs S Pirard S Ansseau M 《Psychological medicine》2002,32(5):935-941
BACKGROUND: A number of challenge studies have reported abnormalities of serotonergic function in borderline personality disorder (BPD). There are, however, problems with the pharmacological probes used in these studies since fenfluramine and m-CPP are not only serotonergic agents but also induce release of catecholamines, particularly dopamine. Therefore, we tested whether subjects with BPD showed a blunted prolactin (PRL) response to flesinoxan, a highly potent and selective 5-HT1A agonist. METHODS: Flesinoxan challenge test was carried out in 20 BPD in-patients and 20 healthy controls matched for gender but not for age. Since 16 BPD in-patients exhibited major depressive co-morbidity, a group of 20 depressed in-patients matched for gender but not for age was also included. RESULTS: BPD in-patients exhibited blunted PRL responses as compared to controls, whereas depressed in-patients did not differ from controls. Moreover, PRL responses were lower among BPD in-patients than among depressed in-patients. Among the BPD in-patients, PRL responses to flesinoxan were lower in patients with past history of suicide attempts (N = 8) than in those with a negative history. CONCLUSIONS: The results show major involvement of serotonergic function in BPD and are consistent with previous studies linking lower serotonergic activity with impulsivity. More particularly, our data suggest that BPD is characterized by lower 5-HT1A receptor sensitivity. Moreover, the data support the involvement of 5-HT1A activity in suicidal behaviour. However, this conclusion is limited because other hormonal responses such as ACTH and cortisol were not assessed, and because BPD was assessed by a self-report questionnaire and not a structured clinical interview. 相似文献
44.
Synthetic peptides corresponding to selected sequences from the nicotinic acetylcholine receptor (AChR) were employed to identify possible antigenic determinants within the receptor which can modulate the anti-AChR response and experimental autoimmune myasthenia gravis (EAMG). Immunization of rabbits with peptides T alpha 73-89, T alpha 351-368, T delta 354-367 and H alpha 351-368, prior to AChR inoculation, affected the course of EAMG in six out of eight rabbits. These six protected rabbits survived three inoculations of AChR and survived for at least five months after the third injection with AChR, whereas control rabbits died following one or two injections of AChR. The survival of peptide-preimmunized rabbits injected with AChR seemed to correlate with the antibody specificities in immunoblots. Following AChR inoculation there was a shift in reactivity, from a subunit-restricted response, to reactivity with all subunits of the receptor. This shift was delayed in protected rabbits. This may indicate that the reactivity with the entire Torpedo receptor molecule represents a loss of tolerance to AChR which culminates in the autoimmune disease, EAMG. 相似文献
45.
H. Denz B. Orth G. Weiss R. Herrmann P. Huber H. Wachter D. Fuchs 《Journal of molecular medicine (Berlin, Germany)》1993,71(1):37-41
Summary Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon- and tumor necrosis factor- are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon- activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon- activity.Abbreviations NHL
non-Hodgkin's lymphoma
- HD
Hodgkin's disease
- MM
multiple myeloma
- MGUS
monoclonal gammopathy of unknown significance
- IFN-
interferon-
- TNF-
tumor necrosis factor- 相似文献
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Pathogenesis of Shigella diarrhea: rabbit intestinal cell microvillus membrane binding site for Shigella toxin 总被引:4,自引:2,他引:4
G Fuchs M Mobassaleh A Donohue-Rolfe R K Montgomery R J Grand G T Keusch 《Infection and immunity》1986,53(2):372-377
This study examined the binding of purified 125I-labeled shigella toxin to rabbit jejunal microvillus membranes (MVMs). Toxin binding was concentration dependent, saturable, reversible, and specifically inhibited by unlabeled toxin. The calculated number of toxin molecules bound at 4 degrees C was 7.9 X 10(10) (3 X 10(10) to 2 X 10(11))/micrograms of MVM protein or 1.2 X 10(6) per enterocyte. Scatchard analysis showed the binding site to be of a single class with an equilibrium association constant, K, of 4.7 X 10(9) M-1 at 4 degrees C. Binding was inversely related to the temperature of incubation. A total of 80% of the labeled toxin binding at 4 degrees C dissociated from MVM when the temperature was raised to 37 degrees C, but reassociated when the temperature was again brought to 4 degrees C. There was no structural or functional change of MVM due to toxin as monitored by electron microscopy or assay of MVM sucrase activity. These studies demonstrate a specific binding site for shigella toxin on rabbit MVMs. The physiological relevance of this receptor remains to be determined. 相似文献
48.
Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis 总被引:5,自引:0,他引:5
D Niederwieser D Fuchs A Hausen G Judmaier G Reibnegger H Wachter C Huber 《Immunobiology》1985,170(4):320-326
In previous publications we showed that neopterin, a pyrazino-pyrimidin compound, represents a biochemical marker for the assessment of cellular immune responses. We thought that the evaluation of this marker molecule might enable insight into the activity of cellular immune responses underlying ulcerative colitis (UC). Evaluation of urinary neopterin excretion in 25 consecutive untreated UC patients revealed striking correlations between neopterin levels and the severity of disease: elevated levels were observed in 9 out of 9 patients with moderately severe to severe, in 3 of 4 with mild and in none of 12 patients with quiescent disease. Further evidence for a correlation between disease activity and neopterin excretion was obtained on the basis of long-term follow-up studies performed in 4 cases. These studies indicated normalization of neopterin levels when clinical remission was achieved. Thereafter, the relative significance of neopterin excretion for determination of clinical stage was assessed by linear correlation analyses and was compared with conventional clinical parameters such as anemia, number of motions per day, raised temperature, ESR and extent of bowel involvement. The logarithm of neopterin excretion and the extent of bowel involvement were the two single parameters most closely related to the clinical stage of ulcerative colitis. We, therefore, conclude that evaluation of neopterin excretion in ulcerative colitis patients represents a new and useful tool for the clinical monitoring of disease activity. 相似文献
49.
Three non-neutralizing monoclonal antibodies were produced and selected against echovirus type 25 JV-4 prototype strain. They were used in an ELISA to investigate the intratypic differentiation of 28 wild isolates. Clinical isolates fell into seven different groups according to their reactivity patterns in ELISA. Two of the non-neutralizing monoclonal antibodies, 9E4 and 6D3, were highly specific, while the third, 6C9, may recognize an epitope common to other types of echoviruses. In contrast, mouse polyclonal antiserum exhibited large cross-reactivities among echovirus serotypes. The reactivity patterns and the geographical origin of the isolates were generally not correlated and, in the same area, four major antigenic variants sometimes coexisted, especially in the south of France. Moreover, reactivity patterns found with ELISA were hardly ever correlated with those observed in a previous study when neutralization tests were used. These results again underline the non-correlation between structure and biological function in the Picornavirus family. 相似文献
50.
1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献