Biomedical subjects

K Yu

Publications and source records attributed to K Yu.

At least 37 records · Page 2Linked to original sources

PubMed2001

Activation of Gadd34 by diverse apoptotic signals and suppression of its growth inhibitory effects by apoptotic inhibitors.

DNA damage has many cellular consequences including, in some cases, apoptosis. Expression of Gadd34 was shown to be increased by ionizing radiation only in cells that undergo rapid apoptosis following this treatment. The effects of various other apoptosis-inducing agents as well as apoptosis-inhibiting genes on regulation of Gadd34 were investigated. In many cell types, agents which have been reported to lead to increased intracellular ceramide levels led to an increase in Gadd34 transcript levels. These included TNFalpha, the ceramide analog C-2 ceramide, dimethyl sphingosine and anti-Fas antibody as well as ionizing radiation. Induction of Gadd34 by ionizing radiation was coincident with the onset of apoptosis and increased as apoptosis progressed. In a short-term transfection assay, more than 30% of Gadd34-transfected cells exhibited nuclear fragmentation by 48 hours. Apoptosis, as well as induction of Gadd34 by apoptotic stimuli, was attenuated by the apoptosis inhibitors, Bcl-2, cowpox virus CrmA and herpes simplex virus ICP34.5. Thus, activation of Gadd34 is a downstream event in apoptotic signaling pathways and may directly contribute to the apoptotic process.

Antigens, Differentiation↗

PubMed2001

CD200 immunoadhesin suppresses collagen-induced arthritis in mice.

DBA/1 mice immunized with 100 microg bovine collagen type II emulsified in Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18 days, develop profound arthritis (>50% of animals) by 30 days postinjection. The molecule CD200 (previously called OX2), associated with, among others, follicular dendritic cells, is implicated in delivery of immunosuppressive signals to the immune system, and an immunoadhesin in which the extracellular domains of CD200 were linked to a mouse IgG2a Fc region has been shown to promote renal allograft survival. DBA/1 mice receiving 15 microg/mouse CD200Fc at 3-day intervals following immunization with collagen did not develop arthritis in this model. Lymphocytes taken from CD200Fc-treated, collagen-immunized mice produced significantly lower levels of TNFalpha and IFN-gamma in culture supernatants after restimulation in vitro with collagen, in contrast to cells taken from control mice treated with PBS or normal mouse Ig. Serum from CD200Fc-treated mice contained less anti-collagen IgG (approximately 50% reduction), with relatively more IgG2b and IgG3, and lower levels of TNFalpha and IFN-gamma, than control mice. These data indicate that this immunoadhesin may have a potent role to play in the regulation of autoimmune disorders.

Animals↗

PubMed2001

Effects of Fe(2+) on ion channels: Na(+) channel, delayed rectified and transient outward K(+) channels.

The effects of Fe(2+) on the properties of three types of ion channels were studied in acutely dissociated rat hippocampal pyramidal neurons from area CA1 at postnatal ages of 7-14 days using the whole cell patch clamp technique. The results indicated that: (1) in the existence of Fe(2+), the activation voltage threshold of transient outward K(+) currents (I(A)) was decreased. The normalized current-voltage curves of activation were well fitted with a single Boltzmann function, and the V(1/2) was 2.44+/-1.14 mV (n=15) in control, whereas 1.79+/-1.53 (n=15), -2.96+/-0.92 (n=14), -5.11+/-1.31 (n=13), -9.05+/-1.64 mV (n=12) in 1, 10, 100 and 1000 microM Fe(2+), respectively. Differences between two groups were significant (P<0.05, n=12-15), except for that between the control and 1 microM (P>0.05, n=15). (2) Fe(2+) caused a left shift of the current-voltage curves of steady-state inactivation of I(A) in a concentration-dependent manner. The curves were well fitted with a single Boltzmann function with similar slope (P>0.05, n=10-13). The V(1/2) were -70.71+/-1.23 (n=13), -71.14+/-1.37 (n=13), -78.21+/-1.17 (n=11), -84.61+/-1.34 (n=12), and -89.68+/-2.59 mV (n=10) in control, 1, 10, 100 and 1000 microM Fe(2+), respectively. Fe(2+) also shifted the current-voltage curves of Na(+) channel steady-state inactivation to more negative depolarization potentials in parallel, with V(1/2), -67.37+/-1.33 mV (n=12) in control, and -67.52+/-1.28 mV (n=12), -68.24+/-1.61 mV (n=10), -71.58+/-1.45 mV (n=10), -76.65+/-1.76 mV (n=9) in 1, 10, 100 and 1000 microM Fe(2+) solutions, respectively. (3) In Fe(2+) solutions, the recovery from inactivation of I(A) was slowed. (4) With application of different concentrations of Fe(2+), the voltage threshold of activation of delayed rectified outward K(+) currents (I(K)) was decreased, while Fe(2+) showed a little inhibition at more positive depolarization. Briefly, the results demonstrated that Fe(2+) is a dose- and voltage-dependent, reversible modulator of I(A), I(K) and Na(+) channels. The results will be helpful to explain the mechanism of Fe(2+) physiological function and Fe(2+) intoxication in the central nervous system.

Animals↗

PubMed2001

Disparate cleavage of poly-(ADP-ribose)-polymerase (PARP) and a synthetic tetrapeptide, DEVD, by apoptotic cells.

In the present investigations, we have shown differential cleavage of cellular PARP and a caspase 3-selective synthetic tetrapeptide substrate, Z-DEVD-AFC or Ac-DEVD-AMC using a T lymphoblastoid cell line Jurkat, and its variant clone E6.1(J-E6). Anti-Fas antibody-mediated apoptosis resulted in DNA fragmentation and PARP cleavage in both Jurkat and J-E6 cells. However, unlike Jurkat, J-E6 cells did not cleave a synthetic tetrapeptide substrate efficiently. The failure to cleave the DEVD tetrapeptide by apoptotic J-E6 cells was not due to insufficient expression or processing of caspase 3 in J-E6 cells. Interestingly, when the J-E6 cells were transiently transfected with a cDNA encoding caspase 3, efficient cleavage of Z-DEVD-AFC was achieved. The observations that apoptotic J-E6 cells barely cleaved a synthetic DEVD tetrapeptide, but efficiently cleaved endogenous PARP, potentially at the most preferred DEVD site, suggest that active caspases may have disparate characteristics to recognize substrates presented in different context.

Apoptosis↗

PubMed2001

Interactions between mastoparan B and the membrane studied by 1H NMR spectroscopy.

Mastoparan B (MP-B) is an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis. NMR spectroscopy was used to study the membrane associated structures of MP-B in various model membrane systems such as 120 mM DPC micelles, 200 mM SDS micelles, and 3%(w/v) DMPC/DHPC (1:2) bicelles. In all systems, MP-B has an amphiphilic alpha-helical structure from Lys2 to Leu14. NOESY experiments performed on MP-B in nondeuterated SDS micelles show that protons in the indole ring of Trp9 are in close contact with methylene protons of SDS micelles. T1 relaxation data and NOE data revealed that the bound form of MP-B may be dominant in SDS micelles. The interactions between MP-B and zwitterionic DPC micelles were much weaker than those between MP-B and anionic SDS micelles. By substitution of Trp9 with Ala9, the pore-forming activity of MP-B was decreased dramatically. All of these results imply that strong electrostatic interactions between the positively charged Lys residues in MP-B and the anionic phospholipid head groups must be the primary factor for MP-B binding to the cell membrane. Then, insertion of the indole ring of Trp9 into the membrane, as well as the amphiphilic alpha-helical structures of MP-B may allow MP-B to span the lipid bilayer through the C-terminal portion. These structural features are crucial for the potent antibiotic activities of MP-B.

Alanine↗

PubMed2001

Estimating the frequency distribution of crossovers during meiosis from recombination data.

Estimation of tetrad crossover frequency distributions from genetic recombination data is a classic problem dating back to Weinstein (1936, Genetics 21, 155-199). But a number of important issues, such as how to specify the maximum number of crossovers, how to construct confidence intervals for crossover probabilities, and how to obtain correct p-values for hypothesis tests, have never been adequately addressed. In this article, we obtain some properties of the maximum likelihood estimate (MLE) for crossover probabilities that imply guidelines for choosing the maximum number of crossovers. We give these results for both normal meiosis and meiosis with nondisjunction. We also develop an accelerated EM algorithm to find the MLE more efficiently. We propose bootstrap-based methods to find confidence intervals and p-values and conduct simulation studies to check the validity of the bootstrap approach.

Algorithms↗

PubMed2001

Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology.

Reactivation of latent tuberculosis contributes significantly to the incidence of disease caused by Mycobacterium tuberculosis. The mechanisms involved in the containment of latent tuberculosis are poorly understood. Using the low-dose model of persistent murine tuberculosis in conjunction with MP6-XT22, a monoclonal antibody that functionally neutralizes tumor necrosis factor alpha (TNF-alpha), we examined the effects of TNF-alpha on the immunological response of the host in both persistent and reactivated tuberculous infections. The results confirm an essential role for TNF-alpha in the containment of persistent tuberculosis. TNF-alpha neutralization resulted in fatal reactivation of persistent tuberculosis characterized by a moderately increased tissue bacillary burden and severe pulmonic histopathological deterioration that was associated with changes indicative of squamous metaplasia and fluid accumulation in the alveolar space. Analysis of pulmonic gene and protein expression of mice in the low-dose model revealed that nitric oxide synthase was attenuated during MP6-XT22-induced reactivation, but was not totally suppressed. Interleukin-12p40 and gamma interferon gene expression in TNF-alpha-neutralized mice was similar to that in control mice. In contrast, interleukin-10 expression was augmented in the TNF-alpha-neutralized mice. In summary, results of this study suggest that TNF-alpha plays an essential role in preventing reactivation of persistent tuberculosis, modulates the pulmonic expression of specific immunologic factors, and limits the pathological response of the host.

Animals↗

PubMed2001

mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer.

The mammalian target of rapamycin (mTOR) is a central regulator of G1 cell cycle protein synthesis that precedes commitment to normal cellular replication. We have studied the effect of cell cycle inhibitor-779 (CCI-779), a rapamycin ester that inhibits mTOR function, on the proliferation of a panel of breast cancer cell lines. Six of eight lines studied were sensitive (IC(50)< or = 50 nM) and two lines were resistant (IC(50)>1.0 microM) to CCI-779. Sensitive lines were estrogen dependent (MCF-7, BT-474, T-47D), or lacked expression of the tumor suppressor PTEN (MDA-MB-468, BT-549), and/or overexpressed the Her-2/neu oncogene (SKBR-3, BT-474). Resistant lines (MDA-MB-435, MDA-MB-231) shared none of these properties. CCI-779 (50 nM) inhibited mTOR function in both a sensitive and a resistant line. In nu/nu mouse xenografts, CCI-779 inhibited growth of MDA-MB-468 (sensitive) but not MDA-MB-435 resistant tumors. Treatment of sensitive lines with CCI-779 resulted in a decrease in D-type cyclin and c-myc levels and an increase in p27(kip-1) levels. There was good correlation between activation of the Akt pathway and sensitivity to CCI-779. Amplification of mTOR-regulated p70S6 kinase, which is downstream of Akt, may also have conferred CCI-779 sensitivity to MCF-7 cells. Taken together, the data suggest that mTOR may be a good target for breast cancer therapy, especially in tumors with Akt activation resulting from either growth factor dependency or loss of PTEN function.

Animals↗

PubMed2001

Survival of Escherichia coli O157:H7 on strawberry fruit and reduction of the pathogen population by chemical agents.

Survival of Escherichia coli O157:H7 was studied on strawberry, a fruit that is not usually washed during production, harvest, or postharvest handling. Two strains of the bacteria were tested separately on the fruit surface or injected into the fruit. Both strains of E. coli O157:H7 survived externally and internally at 23 degrees C for 24 h and at 10, 5, and -20 degrees C for 3 days. The largest reduction in bacterial population occurred at -20 degrees C and on the fruit surface during refrigeration. In all experiments, the bacteria inside the fruit either survived as well as or better than bacteria on the surface, and ATCC 43895 frequently exhibited greater survival than did ATCC 35150. Two strains of E. coli also survived at 23 degrees C on the surface and particularly inside strawberry fruit. Chemical agents in aqueous solution comprising NaOCl (100 and 200 ppm), Tween 80 (100 and 200 ppm), acetic acid (2 and 5%), Na3PO4 (2 and 5%), and H2O2 (1 and 3%) were studied for their effects on reduction of surface-inoculated (10(8) CFU/ml) E. coli O157:H7 populations on strawberry fruit. Dipping the inoculated fruit in water alone reduced the pathogen population about 0.8 log unit. None of the compounds with the exception of H2O2 exhibited more than a 2-log CFU/g reduction of the bacteria on the fruit surface. Three percent H202, the most effective chemical treatment, reduced the bacterial population on strawberries by about 2.2 log CFU/g.

Colony Count, Microbial↗

PubMed2001

[A study on city motor vehicle emission factors by tunnel test].

Applying the principle of tunnel test to run a typical across-river tunnel test in Guangzhou city, 48 h-online-monitor data include pollutant concentration, traffic activity and meteorological data were gained. The average motor vehicle emission factors of NOx, CO, SO2, PM10 and HC were calculated using mass balance which are 1.379, 15.404, 0.142, 0.637, 1.857 g/km. vehicle respectively. Based on that, combined emission factors of 8 types of city vehicles were calculated using linear regression. The result basically showed the character and level of motor vehicle emission in Chinese city.

Vehicle Emissions↗

PubMed2001

[Intraspinal implantation of genetically modified myoblasts with brain-derived neurotrophic factor gene in treating spinal cord injury in rats: neurophysiological study].

OBJECTIVE: To observe the value of gene therapy to spinal cord injury in vivo by transferring gene of brain-derived neurotrophic factor (BDNF) to rat myoblast with retroviral vector electrophysiologically. METHODS: Transection of spinal cord at the level of T9 was produced in 30 adult SD rats that were divided randomly into three groups: BDNF gene modified myoblast implantation (group A), myoblast implantation (group B), and no cell implantation as controls (group C). Three months after operation, whether the axon had regenerated and how the neural function was restored were observed, using the techniques of cerebral somatosensory evoked potential (CSEP) and motor evoked potential (MEP). RESULTS: Three months after injury, 3 rats in group A showed CSEP signals and 5 rats MEP signals, but no electrophysiological response was found in group B or group C. The amplitudes of the recovery of CSEP or MEP signals decreased and their latencies increased as compared with those before injury. The neural function of the spinal cord was greater in group A than in B and C. CONCLUSION: Treatment with genetically modified myoblasts producing BDNF can accelerate recovery from traumatic spinal cord injury in adult rats.

Animals↗

PubMed2001

Recording of spared motor evoked potentials and its augmentation by 4-aminopyridine in chronic spinal cord-injured rats.

OBJECTIVE: To research the direct electrophysiological evidence of discomplete spinal cord injury (SCI) and the effect of 4-aminopyridine on it. METHODS: Motor evoked potentials (MEPs), both spinal cord recorded MEPs (scMEPs) and extracellularly recorded MEPs (exMEPs) were recorded and characterized on a T13 epidural electrode (scMEPs) and an extracellular microelectrode (exMEPs) for 10 normal rats and 40 rats with lesions of various severity (sham, 35 g.cm force (gcf), 70 gcf, 100 gcf impact injury) at the T8-T9 cord using the Allen's drop model. The incline plane and Tarlov techniques were used to assess clinical neurological function. RESULTS: MEPs in the normal rats were elicited by applying transcortical suprathreshold stimulation consisting of 3-4 early negative peaks (N1, N2, N3 and N4) followed by several late waves. The N1 and N2 peaks were largest in the anterior and ventrolateral funiculus, respectively, which was indicative of extrapyramidal pathways. The 100 gcf impact injuries and the cord transection abolished the MEP distal to the lesion, whereas the 35 gcf injuries resulted in a latency shift and amplitude decrement of the MEP peaks. Eighteen of the 20 rats with 70 gcf-injuries showed clinical paraplegia. Among them, 7 rats had neurophysiological evidence of residual conduction pathways through the lesioned cord segment, such as the presence of N1 and N2 peaks in the scMEPs or exMEPs. After 4-aminopyridine (4-AP) administrations (1 mg/kg), the amplitude of the spared exMEP increased significantly and spread more widely. CONCLUSIONS: MEPs evoked by transcortical stimulation travel mostly in the extrapyramidal tract. MEP monitoring could provide an excellent method of detecting the functional integrity of the motor tracts after SCI, and could even detect spared motor fibers after discomplete SCI. Furthermore, the use of 4-AP or other K+ channel blocking agents may be a potential treatment for patients with chronic moderate to severe SCI.

4-Aminopyridine↗

PubMed2001

The preliminary experimental study of induced differentiation of embryonic stem cells into corneal epithelial cells.

PURPOSE: To study preliminarily induced differentiation of embryonic stem cells into corneal epithelial cells in vitro. METHODS: Murine embryonic stem cells were co-cultured with Rabbit limbal corneal epithelial cells in Transwell system to induce differentiation. Mophological and immunohistochemical examination were implemented. RESULTS: The induced cells from embryonic stem cells have an epithelial appearance. The cells formed a network and were confluent into film gradually after being co-cultured with rabbit limbal corneal epithelial cells for 24-96 hours. The cells ranged mosaic structure and localized together with clear rim. Most of the cells showed polygonal appearance. Transmission electron microscope showed lots of microvilli on the surface of induced cells and tight junctions between them. These epithelial-like cells expressed the corneal epithelial cell specific marker cytokeratin3/cytokeratin12. CONCLUSION: The potential mechanism of the differentiation of murine embryonic stem cells into corneal epithelial cells induced by limbal corneal epithelial cell-derived inducing activity is to be further verified.

Animals↗

PubMed2000

Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome.

Craniosynostosis syndromes are autosomal dominant human skeletal diseases that result from various mutations in fibroblast growth factor receptor genes (Fgfrs). Apert syndrome (AS) is one of the most severe craniosynostosis syndromes and is associated with severe syndactyly of the hands and feet and with central nervous system malformations. AS is caused by specific missense mutations in one of two adjacent amino acid residues (S252W or P253R) in the highly conserved region linking Ig-like domains II and III of FGFR2. Here we demonstrate that these mutations break one of the cardinal rules governing ligand specificity of FGFR2. We show that the S252W mutation allows the mesenchymal splice form of FGFR2 (FGFR2c) to bind and to be activated by the mesenchymally expressed ligands FGF7 or FGF10 and the epithelial splice form of FGFR2 (FGFR2b) to be activated by FGF2, FGF6, and FGF9. These data demonstrate loss of ligand specificity of FGFR2 with retained ligand dependence for receptor activation. These data suggest that the severe phenotypes of AS likely result from ectopic ligand-dependent activation of FGFR2.

3T3 Cells↗

PubMed2000

Receptor engagement on cells expressing a ligand for the tolerance-inducing molecule OX2 induces an immunoregulatory population that inhibits alloreactivity in vitro and in vivo.

Increased survival of C57BL/6 renal allografts following portal vein donor-specific pretransplant immunization of C3H mice is associated with increased expression of the molecule OX2 seen on host dendritic cells, along with a marked polarization in cytokine production from lymphocytes harvested from the transplanted animals, with preferential production of IL-4, IL-10, and TGF-beta on donor-specific restimulation in vitro, and decreased production of IL-2, IFN-gamma, and TNF-alpha compared with non-portal vein-immunized control transplanted mice. The increased renal allograft survival and the altered cytokine production are abolished by infusion of anti-mouse OX2 mAb (3B6). Infusion of a soluble OX2:Fc immunoadhesin can itself produce significant prolongation of xeno- and allografts in mice. We have used FITC-conjugated OX2:Fc to characterize cells expressing a ligand (OX2L) for OX2, and provide evidence that subpopulations of LPS-stimulated splenic macrophages, Con A-activated splenic T cells, and the majority (>80%) of gammadeltaTCR(+) T cells express this ligand. We show below that F4/80(+), OX2L(+) splenic macrophages, admixed with OX2:Fc, represent a potent immunosuppressive population capable of causing more profound inhibition of alloreactivity in vitro or in vivo than that seen using either OX2:Fc or OX2(+) (or OX2L(+)) cells alone. Immunoregulation by this OX2L(+) population occurs in an MHC-restricted fashion.

Animals↗

PubMed2000

Characterization of a pituitary GnRH-receptor from a perciform fish, Morone saxatilis: functional expression in a fish cell line.

Gonadotropin-releasing hormones (GnRHs) bind to the specific receptor present on the gonadotrophs to activate the synthesis and release of gonadotropins (follicle stimulating hormone or FSH and luteinizing hormone or LH), which in turn control gonadal maturation, gametogenesis and gamete release. Perciform species have three endogenous GnRHs. The main objective of this study was to characterize the gonadotropin-releasing hormone receptor (GnRH-R) present in the pituitary of a perciform species, striped bass (Morone saxatilis) and demonstrate how it interacts with its potential ligand. In this study, a cDNA for GnRH-R from the pituitaries of striped bass was cloned. The cloned cDNA has an open reading frame (ORF) that codes for a 419 amino acids peptide. Like other G-protein coupled receptors including the non-mammalian GnRH-Rs, the peptide has seven putative transmembrane domains and a C-terminal tail. Comparative analysis of the amino acid sequence of striped bass (stb) GnRH-R shows 38-87% similarity with the known GnRH-Rs. A Northern blot analysis revealed a single GnRH-R transcript in the pituitary; however, its expression in various extrapituitary tissues was demonstrated by a reverse-transcription-PCR (RT-PCR). Functionally, upon induction by endogenous forms of GnRHs (seabream, chicken II and salmon GnRHs) and a mammalian GnRH-agonist, the recombinant stbGnRH-R mediated a reporter gene (luciferase) activity in a fish cell line (CHSE-214). A real-time relative quantitation method established that significantly higher (P<0.05) levels of stbGnRH-R mRNA were present in the pituitaries of striped bass with advanced stages of ovarian development, compared to the pituitaries of fish with less developed ovaries.

Amino Acid Motifs↗

PubMed2000

Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2.

Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4(+) T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4(+) T cells in preventing reactivation in a murine model of latent tuberculosis. Antibody-mediated depletion of CD4(+) T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4(+) T cells are believed to be a major source of interferon (IFN)-gamma, expression of the gene for IFN-gamma in the lungs of CD4(+) T cell-depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4(+) T cell depletion, indicating that macrophage activation was present even during CD4(+) T cell deficiency. These data indicate that CD4(+) T cells are necessary to prevent reactivation but may have roles in addition to IFN-gamma production and macrophage activation in controlling a persistent tuberculous infection.

Animals↗

PubMed2000

Demand characteristics of residential substance abuse treatment programs.

PURPOSE: This study examined the objective demand characteristics of treatment programs in which substance abuse patients, or psychiatric patients, were residing. It also examined associations of objective demand with substance abuse patients' perceived expectations for functioning during treatment and patients' in-program participation. METHODS: A total of 994 patients living in 79 programs took part. RESULTS: When patients had a substance abuse rather than a psychiatric problem, objective demand was higher: program policies had higher requirements for functioning and more resident control; programs offered fewer health-treatment services; and the physical design provided fewer safety features and social-recreational aids. Compared to substance abuse patients in low-demand programs, patients in high-demand programs perceived the program to have higher expectations, in that the treatment climate exerted more press to develop relationships, set goals, and be organized. Patients in high-demand programs engaged more in self-initiated activities and participated more in treatment services and program-organized events. Substance abuse patients' activity and participation levels were determined jointly by the level of demand and by the expectations for patients' expressiveness and self-understanding of their personal problems. IMPLICATIONS: The findings illustrate the importance of considering objective indices of demand in conjunction with perceived expectations to improve patients' treatment outcomes.

Adult↗