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Biomedical subjects

C C Chen

Publications and source records attributed to C C Chen.

At least 19 recordsLinked to original sources
PubMed1999

Role of the cyclic AMP-protein kinase A pathway in lipopolysaccharide-induced nitric oxide synthase expression in RAW 264.7 macrophages. Involvement of cyclooxygenase-2.

The signaling pathway for lipopolysaccharide (LPS)-induced nitric oxide (NO) release in RAW 264.7 macrophages involves the protein kinase C and p38 activation pathways (Chen, C. C., Wang, J. K., and Lin, S. B. (1998) J. Immunol. 161, 6206-6214; Chen, C. C., and Wang, J. K. (1999) Mol. Pharmacol. 55, 481-488). In this study, the role of the cAMP-dependent protein kinase A (PKA) pathway was investigated. The PKA inhibitors, KT-5720 and H8, reduced LPS-induced NO release and inducible nitric oxide synthase (iNOS) expression. The direct PKA activator, Bt(2)cAMP, caused concentration-dependent NO release and iNOS expression, as confirmed by immunofluorescence studies. The intracellular cAMP concentration did not increase until after 6 h of LPS treatment. Two cAMP-elevating agents, forskolin and cholera toxin, potentiated the LPS-induced NO release and iNOS expression. Stimulation of cells with LPS or Bt(2)cAMP for periods of 10 min to 24 h caused nuclear factor-kappaB (NF-kappaB) activation in the nuclei, as shown by detection of NF-kappaB-specific DNA-protein binding. The PKA inhibitor, H8, inhibited the NF-kappaB activation induced by 6- or 12-h treatment with LPS but not that induced after 1, 3, or 24 h. The cyclooxygenase-2 (COX-2) inhibitors, NS-398 and indomethacin, attenuated LPS-induced NO release, iNOS expression, and NF-kappaB DNA-protein complex formation. LPS induced COX-2 expression in a time-dependent manner, and prostaglandin E(2) production was induced in parallel. These results suggest that 6 h of treatment with LPS increases intracellular cAMP levels via COX-2 induction and prostaglandin E(2) production, resulting in PKA activation, NF-kappaB activation, iNOS expression, and NO production.

Animals↗
PubMed1999

Colour doppler imaging for diagnosis of intracranial hypotension.

BACKGROUND: Measurement of CSF pressure is the only known way to confirm the diagnosis of intracranial hypotension. We aimed to assess colour doppler flow imaging (CDFI) for measurement of blood flow of the superior ophthalmic vein for the diagnosis of intracranial hypotension. METHODS: We enrolled 25 consecutive patients with orthostatic headache who had clinical features of intracranial hypotension. We defined low-pressure headache as cerebrospinal-fluid pressure below 60 mm H2O. We used CDFI to measure the diameter and maximum flow velocity of the superior ophthalmic vein in all patients. Magnetic resonance imaging of the brain and lumbar puncture with measurement of cerebrospinal-fluid pressure within 24 h were also done after sonographic examination. The control group comprised 13 healthy individuals of a similar age; in addition, those patients who had orthostatic headache without low pressure served as a control group for the patients. FINDINGS: Of the 25 patients recruited for this study, 13 satisfied the criteria for low-pressure headache. The remaining 12 patients with normal cerebrospinal-fluid pressure had transformed migraine (five patients) or chronic tension-type headache (seven patients), and therefore served as the control group for the patients. The mean diameter of the superior ophthalmic vein was substantially larger in the patients with intracranial hypotension (3.9 [SD 0.2] mm) than in the healthy controls (2.6 [0.4] mm) and the controls from the patients' group (2.7 [0.2] mm) (p<0.0001). The mean maximum flow velocity was significantly higher in the intracranial-hypotension group (17.0 [SD 3.4] cm/s) than in the healthy controls (7.9 [1.1] cm/s) and the other patients (7.3 [1.7] cm/s) (p<0.0001). Seven patients with intracranial hypotension were reassessed after treatment with epidural blood patch. After this treatment the clinical symptoms were relieved and there was a striking reversal of the superior ophthalmic vein flow. INTERPRETATION: CDFI to measure blood flow of the superior ophthalmic vein provides a practical, simple, and non-invasive diagnostic method for suspected intracranial hypotension.

Adult↗
PubMed1999

Activation-dependent adhesion of human platelets to Cyr61 and Fisp12/mouse connective tissue growth factor is mediated through integrin alpha(IIb)beta(3).

Cyr61 and connective tissue growth factor (CTGF), members of a newly identified family of extracellular matrix-associated signaling molecules, are found to mediate cell adhesion, promote cell migration and enhance growth factor-induced cell proliferation in vitro, and induce angiogenesis in vivo. We previously showed that vascular endothelial cell adhesion and migration to Cyr61 and Fisp12 (mouse CTGF) are mediated through integrin alpha(v)beta(3). Both Cyr61 and Fisp12/mCTGF are present in normal blood vessel walls, and it has been demonstrated that CTGF is overexpressed in advanced atherosclerotic lesions. In the present study, we examined whether Cyr61 and Fisp12/mCTGF could serve as substrates for platelet adhesion. Agonist (ADP, thrombin, or U46619)-stimulated but not resting platelets adhered to both Cyr61 and Fisp12/mCTGF, and this process was completely inhibited by prostaglandin I(2), which prevents platelet activation. The specificity of Cyr61- and Fisp12/mCTGF-mediated platelet adhesion was demonstrated by specific inhibition of this process with polyclonal anti-Cyr61 and anti-Fisp12/mCTGF antibodies, respectively. The adhesion of ADP-activated platelets to both proteins was divalent cation-dependent and was blocked by RGDS, HHLGGAKQAGDV, or echistatin, but not by RGES. Furthermore, this process was specifically inhibited by the monoclonal antibody AP-2 (anti-alpha(IIb)beta(3)), but not by LM609 (anti-alpha(v)beta(3)), indicating that the interaction is mediated through integrin alpha(IIb)beta(3). In a solid phase binding assay, activated alpha(IIb)beta(3), purified by RGD affinity chromatography, bound to immobilized Cyr61 and Fisp12/mCTGF in a dose-dependent and RGD-inhibitable manner. In contrast, unactivated alpha(IIb)beta(3) failed to bind to either protein. Collectively, these findings identify Cyr61 and Fisp12/mCTGF as two novel activation-dependent adhesive ligands for the integrin alpha(IIb)beta(3) on human platelets, and implicate a functional role for these proteins in hemostasis and thrombosis.

Animals↗
PubMed1999

Paternal monoallelic expression of the paired immunoglobulin-like receptors PIR-A and PIR-B.

A diverse pattern of polymorphism is defined for the paired Ig-like receptors (PIRs) that serve as activating (PIR-A) and inhibitory (PIR-B) receptors on B lymphocytes, dendritic cells, and myeloid-lineage cells in mice. The monoclonal anti-PIR antibody 10.4 is shown to recognize an allelic PIR-A/PIR-B determinant on cells from BALB/c but not C57BL/6 mice. Other strains of inbred mice also can be typed on the basis of their expression of this PIR allelic determinant. Analysis of (BALB/c x C57BL/6) F1 hybrid offspring indicates that PIR molecules bearing the paternal PIR allotype are expressed whereas PIR-A and PIR-B molecules bearing the maternal allotype are not. The monoallelic expression of the polymorphic PIR-A and PIR-B molecules, and possibly of their human Ig-like transcript/leukocyte Ig-like receptor/monocyte/macrophage Ig-like receptor and killer cell inhibitory receptor relatives, may influence innate and specific immune responses in outbred populations.

Alleles↗
PubMed1999

Activation of indices of cell-mediated immunity in bipolar mania.

BACKGROUND: Evidence supports that macrophages as well as lymphocytes and their products may be involved in the pathophysiology of psychiatric disorders. Whether patients with bipolar disorder have activation or reduction of immunity during a manic episode remains unclear. METHODS: The purpose of this case-control study was to investigate the lymphocyte proliferation to phytohemagglutinin (PHA), concanavalin A, and pokeweed mitogen, and plasma levels of soluble interleukin-2 receptor (sIL-2R) and sIL-6R in patients with bipolar mania (DSM-III-R). The subjects were 23 physically healthy patients with Young Mania Rating Scale (YMRS) scores > or = 26 as well as aged < or = 45 years and 23 age- and gender-matched normal control subjects. The above immune variables were measured in acute mania and consequent remission (YMRS scores < or = 12) among bipolar patients. RESULTS: The lymphocyte proliferation to PHA and the plasma sIL-2R levels, but not sIL-6R, of bipolar patients were significantly higher in acute mania than in consequent remission. These elevations were not due to differences in medication status. Only in acute mania were the plasma sIL-2R levels of patients significantly higher than control subjects. A positive correlation between the changes of manic severity and plasma sIL-2R levels was observed. Remitted bipolar patients and normal control subjects did not differ in any of these measures. CONCLUSIONS: Cell-mediated immunity activation in bipolar mania was demonstrated and may be through a specifically state-dependent immune response.

Acute Disease↗
PubMed1999

Biochemical nature and cellular distribution of the paired immunoglobulin-like receptors, PIR-A and PIR-B.

PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively, by multiple Pira genes and a single Pirb gene in mice, are relatives of the human natural killer (NK) and Fc receptors. Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of approximately 85 and approximately 120 kD on B cells, granulocytes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcRgammac) chain. Whereas PIR-B fibroblast transfectants expressed cell surface molecules of approximately 120 kD, PIR-A transfectants expressed the approximately 85-kD molecules exclusively intracellularly; PIR-A and FcRgammac cotransfectants expressed the PIR-A/ FcRgammac complex on their cell surface. Correspondingly, PIR-B was normally expressed on the cell surface of splenocytes from FcRgammac-/- mice whereas PIR-A was not. Cell surface levels of PIR molecules on myeloid and B lineage cells increased with cellular differentiation and activation. Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not. These experiments define the coordinate cellular expression of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; demonstrate the requirement of FcRgammac chain association for cell surface PIR-A expression; and suggest that the level of FcRgammac chain expression could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.

Animals↗
PubMed1999

Psychophysical study of noxious and innocuous cold discrimination in monkey.

Psychophysical evidence shows that humans are better able to distinguish differences in the intensity of cutaneous temperature in the cool range than in the noxious cold range. In order to compare these human perceptual findings with physiological data from non-human primates, we performed similar psychophysical experiments of cold perception in monkeys. Two adult male rhesus monkeys were trained to detect cooling shifts from baseline temperatures between 0 degrees and 22 degrees C applied to the face with a 1-cm2 contact thermode. Detection thresholds were determined using the method of constant stimuli for one monkey and an adaptive psychophysical algorithm which insured constant behavioral performance for the other monkey. Results showed that both monkeys detected significantly smaller temperature decreases from innocuous cool baselines (i.e., 22 degrees and 16 degrees C) than from noxious and near-noxious baselines (10 degrees, 6 degrees, 0 degrees C). Similarly, the latencies for detecting the cooling shifts were shorter and less variable in the innocuous cool range than in the noxious cold range. The observation of more precise discrimination of innocuous cool than noxious cold temperatures in monkeys is consistent with human psychophysical data. Thus, these data suggest that differential patterns of neuronal activity evoked by cool and noxious cold cutaneous stimuli, observed in peripheral afferents as well as in the central nervous system of monkey and cat, probably also exist in the human.

Adaptation, Physiological↗
PubMed1999

Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man.

BACKGROUND: In animal studies, atrial fibrillation has been shown to shorten the atrial refractory period and impair its rate adaptation. However, little is known about the effects of chronic atrial fibrillation on atrial electrophysiology and its recovery course in humans. METHODS AND RESULTS: Nineteen patients, mean age 64 +/- 14 years, with chronic atrial fibrillation of more than six months duration were included in this study. All of them were successfully converted to sinus rhythm with an external defibrillator. Atrial effective refractory periods at right atrial appendage and distal coronary sinus were determined with five pacing cycle lengths (300, 400, 500, 600 and 700 ms) at 30 min after cardioversion and once a day for four days. The atrial conduction properties, including P wave duration of surface ECG, and right and left atrial conduction times, were also measured at the same time interval. Twenty age-matched patients without a history of atrial tachyarrhythmia were evaluated as controls. In comparison with controls, chronic atrial fibrillation significantly shortened the atrial effective refractory period, impaired its rate adaptation response, especially at distal coronary sinus, and depressed the conduction properties of atria. The atrial conduction properties did not change during the four-day follow-up period; however, the atrial effective refractory period was gradually prolonged and its rate adaptation response improved after restoration of sinus rhythm. CONCLUSIONS: In humans, chronic atrial fibrillation significantly shortened the atrial effective refractory period, and impaired its rate adaptation response. Restoration and maintenance of sinus rhythm could reverse these electrophysiological changes.

Aged↗
PubMed1999

A letter-recognition task to assess lingual tactile acuity.

PURPOSE: This study evaluated a novel neurosensory test based on letter recognition developed for the assessment of spatial acuity of the tongue. PATIENTS AND METHODS: An up-down tracking procedure was used to estimate the threshold height for the recognition of embossed letters of the alphabet examined by the tongue tip. The 48 stimuli consisted of acrylic strips, one side of which bore a letter (A, I, J, L, O, T, U, or W) of 3, 4, 5, 6, 7, or 8 mm in height. Twenty neurologically normal young adults were tested. RESULTS: Stable estimates of the threshold height were obtained after delivery of only 15 trials. Threshold height averaged 5.1 mm (range, 3.7 to 6.6 mm) and was unaffected by gender (P>.88). Although the letters were identified correctly 54% of the time, on average, the tangibility of individual letters varied from 5% correct (for W) to 82% correct (for T). The letter W was never identified by 16 of 20 subjects; T, O, and U were identified by all subjects. Analysis of errors confirmed that subjects relied on spatial cues to make the discriminations; 58% of the incorrect responses were made to 1 or 2 letters with spatial features similar to those of the stimulus letter. CONCLUSIONS: The threshold height for letter recognition can be obtained easily and rapidly, exhibits low among-subject variability, and reflects the capacity to extract and process spatial information. Letters of similar legibility on the tongue should be used to minimize underestimation of subjects' true acuities.

Adolescent↗
PubMed1999

Safrole-induced oxidative damage in the liver of Sprague-Dawley rats.

Safrole is a weak hepatocarcinogen, and its carcinogenic effect has been linked to the formation of stable safrole DNA adducts. In this study, we tested whether safrole also induces oxidative damages in Sprague-Dawley rats. By single i.p. injection, safrole dose-dependently induced the formation of hepatic lipid hydroperoxides (LHP) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). The safrole-induced LHP reached peak level on day 3 and gradually returned to the basal level on day 15. On the other hand, 8-OH-dG levels from the similarly treated rats peaked on day 5 and returned to basal level on day 15. Safrole also dose-dependently induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. We also examined the protective effect of vitamin E, deferoxamine and N-acetylcysteine against the safrole-induced oxidative damage. N-Acetylcysteine, the precursor of glutathione, exerted the greatest protective effect among the three antioxidants tested. In contrast, buthionine sulfoximine, the glutathione synthesis inhibitor, enhanced the safrole-induced oxidative damage, as evidenced by the elevation of LHP and 8-OH-dG levels on day 3 (P<0.05). These findings demonstrate that safrole treatment induces oxidative damage in rat hepatic tissue, and glutathione plays an important protective role. This oxidative damage may be involved in the hepatocarcinogenic effect of safrole.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Synergistic effect of arachidonic acid and cyclic AMP on glucose transport in 3T3-L1 adipocytes.

The combined effect of arachidonic acid and cAMP on glucose transport was examined in 3T3-L1 adipocytes. In cells pre-treated with arachidonic acid and increasing concentrations of 8-bromo cAMP for 8 h, although either agent alone enhanced glucose uptake, the simultaneous presence of both agents dramatically increased 2-deoxyglucose uptake in a synergistic fashion. Insulin-stimulated glucose transport, on the other hand, was only slightly affected. The synergistic effect of these two agents was abolished in the presence of cycloheximide. Immunoblot analysis revealed that the contents of ubiquitous glucose transporter (GLUT1) in total cellular and plasma membranes were similarly augmented in cells pre-treated with both arachidonic acid and 8-bromo cAMP, to a greater extent than the additive effect of each agent alone. The content of GLUT4, on the other hand, was not altered under the same experimental conditions. In cells pre-treated with 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) for 24 h to down-regulate protein kinase C (PKC), the subsequent synergistic effect of arachidonic acid and 8-bromo cAMP was greatly inhibited. In addition, pre-treatment with both PMA and 8-bromo cAMP enhanced glucose transport in a similarly synergistic fashion. Thus the present study seems to indicate that arachidonic acid may act with cAMP in a synergistic way to increase glucose transport by a PKC-dependent mechanism. The increased activity may be accounted for by increased GLUT1 synthesis.

3T3 Cells↗
PubMed1999

Effect of stimulation of an upper limb on motor evoked potentials in lower limb muscles to transcranial magnetic stimulation in normal subjects and patients with thalamic infarction.

The effects of conditioning stimulation of an upper limb on motor evoked potentials (MEPs) of relaxed muscles in both lower limbs were studied in 7 normal subjects and two patients with left thalamic infarction. A possible mechanism for the Jendrassik maneuver (JM) is that induced proprioceptive input ascends supraspinally to facilitate the descending volleys. In order to mimic the JM with a more controlled influence, we used an electrical conditioning (C) stimulation (4 times sensory threshold) delivered to the left index finger preceding the transcranial (T) magnetic stimulation at C-T intervals of 0-200 ms. The MEP facilitation of bilateral tibialis anterior (TA) and gastrocnemius medialis (GC) was within C-T 70-110 ms. The peak facilitation was at C-T 80 ms for ipsilateral TA (309%) and GC (405%) and at C-T 90 ms for contralateral TA (207%) and GC (283%). In the two thalamic infarction patients with right-sided sensory loss, the facilitation did not occur when the conditioning stimulation was delivered to the affected index finger. Therefore, it is likely that the peripheral volley must be transmitted supraspinally to facilitate MEPs of the lower limbs. This method for studying sensory facilitation is more quantitative and reproducible than the JM and technically better than other previously described methods for somatosensory conditioning.

Adult↗
PubMed1999

Antioxidant principles from Ephemerantha lonchophylla.

One dihydrostilbene and three phenanthrene antioxidants were isolated from an ethanolic extract of the Chinese herbal Ephemerantha lonchophylla. One of these compounds, ephemeranthone (4) is a new natural product. Denbinobin (1) and 3-methylgigantol (3) have been previously isolated from this plant, and 3-ethoxy-5-hydroxy-7-methoxy-1,4-phenanthraquinone (2) is an artifact. The structures of these compounds were determined by spectroscopic analysis. The antioxidative activities for inhibiting human low density lipoprotein oxidation in vitro of compounds 1-4 were determined, and only 4 was active (5.3 times that of probucol).

Antioxidants↗
PubMed1999

Attenuation of house dust mite Dermatophagoides farinae-induced airway allergic responses in mice by dehydroepiandrosterone is correlated with down-regulation of TH2 response.

BACKGROUND: Dehydroepiandrosterone (DHEA), an abundant androgen in circulation, has important immunomodulating effects on T-cell differentiation; however, it is not known whether this hormone influences allergic responses. OBJECTIVE: We have established a murine model of airway inflammation induced by house dust mite Dermatophagoides farinae (Der f). Der f challenge of sensitized mice would elicit a pulmonary eosinophilic inflammation. In the present study, we employed this model system to explore the effect of DHEA on allergic responses. METHODS: Female BALB/c mice were fed with a standard diet incorporated with 1.5% (w/w) of DHEA for 1 week before sensitization and every other day for an additional 2 weeks after sensitization. After intratracheal inoculation of allergen, the Der f-induced airway inflammation, immunoglobulin (Ig)E antibody production, and cytokine expression were compared between control and DHEA-fed mice. RESULTS: In control mice the Der f-induced eosinophilia in bronchoalveolar lavage (BAL) fluids was accompanied by an increase in production of interleukin (IL)-4, IL-5, and interferon IFN-gamma systemically and locally. DHEA supplementation did not affect the body weight of mice. However, in mice that were receiving DHEA, the numbers of eosinophils and lymphocytes in BAL fluids significantly decreased at days 2 and 6 after challenge as compared with control mice. Concomitantly, total IgE antibody concentrations as well as IL-4, IL-5, and IFN-gamma levels in BAL fluids or serum also significantly reduced. Immunocytochemical staining of BAL cells revealed that there were fewer IL-4-, IL-5-, IL-10-, but not IFN-gamma-positive stained cells in DHEA-fed mice than in mice who consumed unsupplemented diet. Reverse transcription-polymerase chain reaction analysis demonstrated DHEA decreased the expression of IL-5 and IL-10 transcripts in BAL cells. CONCLUSIONS: Our results showed that administration of DHEA during allergic sensitization could attenuate the subsequent allergic responses elicited by challenge, and that the suppressive effect of DHEA was associated with a down-regulation of TH2 response.

Animals↗
PubMed1999

Neurotrophins differentially regulate the survival and morphological complexity of human CNS model neurons.

To determine the effect of neurotrophins on the survival and morphological differentiation of CNS neurons, we examined NT2-N cells, which provide a unique culture model for terminally differentiated and polar human neurons. Here we report the development of conditions for the long-term culture of NT2-N cells in low density and in chemically defined medium. We show that NT2-N cells express rRNAs for TrkA, TrkB, and TrkC tyrosine kinase receptors and the low-affinity nerve growth factor receptor (p75NTR). All members of the nerve growth factor-related family of neurotrophic factors promote neuronal survival in long-term cultures with approximately 1 ng/ml for half-maximal survival. At high concentrations (>20 ng/ml), the neurotrophins reversed the survival-promoting effect as judged by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] conversion. In contrast to the uniform effect of all neurotrophins on neuronal survival, brain-derived neurotrophic factor selectively induced an increased dendritic complexity. These results demonstrate that NT2-N cells provide a useful model to analyze the effect of neurotrophins on the survival and morphological differentiation of CNS neurons in vitro. In addition, the data indicate that neuronal survival and the development of morphological complexity are differentially regulated in a multireceptor context.

Brain-Derived Neurotrophic Factor↗
PubMed1999

Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism.

The genes that encode the major enzymes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), exhibit functional polymorphism. The variant alleles ADH2*2 and ADH3*1, which encode high-activity ADH isoforms, and the ALDH2*2 allele, which encodes the low-activity form of ALDH2, protect against alcoholism in East Asians. To investigate possible interactions among these protective genes, we genotyped 340 alcoholic and 545 control Han Chinese living in Taiwan at the ADH2, ADH3, and ALDH2 loci. After the influence of ALDH2*2 was controlled for, multiple logistic regression analysis indicated that allelic variation at ADH3 exerts no significant effect on the risk of alcoholism. This can be accounted for by linkage disequlibrium between ADH3*1 and ADH2*2 ALDH2*2 homozygosity, regardless of the ADH2 genotypes, was fully protective against alcoholism; no individual showing such homozygosity was found among the alcoholics. Logistic regression analyses of the remaining six combinatorial genotypes of the polymorphic ADH2 and ALDH2 loci indicated that individuals carrying one or two copies of ADH2*2 and a single copy of ALDH2*2 had the lowest risk (ORs 0.04-0.05) for alcoholism, as compared with the ADH2*1/*1 and ALDH2*1/*1 genotype. The disease risk associated with the ADH2*2/*2-ALDH2*1/*1 genotype appeared to be about half of that associated with the ADH2*1/*2-ALDH2*1/*1 genotype. The results suggest that protection afforded by the ADH2*2 allele may be independent of that afforded by ALDH2*2.

Adult↗
PubMed1999

Using imperfect secondary structure predictions to improve molecular structure computations.

MOTIVATION: Until ab initio structure prediction methods are perfected, the estimation of structure for protein molecules will depend on combining multiple sources of experimental and theoretical data. Secondary structure predictions are a particularly useful source of structural information, but are currently only approximately 70% correct, on average. Structure computation algorithms which incorporate secondary structure information must therefore have methods for dealing with predictions that are imperfect. EXPERIMENTS PERFORMED: We have modified our algorithm for probabilistic least squares structural computations to accept 'disjunctive' constraints, in which a constraint is provided as a set of possible values, each weighted with a probability. Thus, when a helix is predicted, the distances associated with a helix are given most of the weight, but some weights can be allocated to the other possibilities (strand and coil). We have tested a variety of strategies for this weighting scheme in conjunction with a baseline synthetic set of sparse distance data, and compared it with strategies which do not use disjunctive constraints. RESULTS: Naive interpretations in which predictions were taken as 100% correct led to poor-quality structures. Interpretations that allow disjunctive constraints are quite robust, and even relatively poor predictions (58% correct) can significantly increase the quality of computed structures (almost halving the RMS error from the known structure). CONCLUSIONS: Secondary structure predictions can be used to improve the quality of three-dimensional structural computations. In fact, when interpreted appropriately, imperfect predictions can provide almost as much improvement as perfect predictions in three-dimensional structure calculations.

Algorithms↗