Zika virus antibody-positivity among symptomatic/asymptomatic pregnant women in the Aseer region displays pre-exposure to dengue viruses.

Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.

Nonlinear Rayleigh wave propagation in a layered half-space in dual-phase-lag.

We investigate nonlinear Rayleigh wave propagation in a layered thermoelastic medium composed of a slab rigidly bonded to the surface of a half-space under prescribed external thermal boundary conditions within the dual-phase-lag theory. The heat conduction coefficient for both the slab and the matrix have a linear dependence on temperature. Our aim is to assess the effect of temperature dependence of the heat conductivity, as well as the thermal relaxation times, on the process of wave propagation in the layered medium. Poincaré expansion of the solution in a small parameter and the generation of higher harmonics allow to evaluate the coefficient of this nonlinear coupling in the slab through heat wave propagation measurement. For the used numerical values, the results show that some characteristics of the problem, e.g. the temperature, heat flux and one stress component suffer jumps at the interface, while the other stress components are continuous there. The jump in the heat flux is noticeable only in the first order of nonlinearity. The existence of jumps at the interface may be of interest for measurements. Comparison with the case of the half-space showed that the presence of the slab contributes to faster damping of the solution with depth in the half-space.

Zika virus antibody-positivity among symptomatic/asymptomatic pregnant women in the Aseer region displays pre-exposure to dengue viruses

@#Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.

Nonlinear Rayleigh wave propagation in thermoelastic media in dual-phase-lag.

A model of generalized thermoelasticity within dual-phase-lag is used to investigate nonlinear Rayleigh wave propagation in a half-space of a transversely isotropic elastic material. It is assumed that the coefficient of heat conduction is temperature-dependent, a fact that plays an important role in the coupling behaviour analysis of thermoelastic and piezo-thermoelastic solids. Taking such a dependence into account becomes a necessity at higher temperatures and in nano-structures, when the material properties can no longer be considered as constants. Normal mode analysis is applied to find a particular solution to the problem under consideration. A concrete case is solved under prescribed boundary conditions and tentative values of the different material coefficients. The results are discussed to reveal the effect of temperature dependence of the heat conduction coefficient, as well as the thermal relaxation times, on nonlinear Rayleigh wave propagation. All quantities of practical interest are illustrated in two-and three-dimensional plots. The presented results may be useful in the detection of the second harmonic amplitudes through measurements related to the propagating heat wave.

Chemosensitizing Effect of Cernumidine Extracted from Solanum cernuum on Bladder Cancer Cells in Vitro.

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin. The combination of CER+cDDP inhibited cell migration on T24 cells. CER+cDDP down-regulated MMP-2/9 and p-ERK1/2, while it increased EGFR activity corroborating the observed cell migration inhibition. Down-regulation of Bcl-2 and up-regulation pro-apoptotic Bax and further depletion of the mitochondrial membrane potential (ΔΨm) indicates that mitochondria play a central role in the combination treatment inducing the mitochondrial signaling pathway of apoptosis in T24 cells. Our data showed that the alkaloid cernumidine is worthy of further studies as a chemosensitizing agent to be used in complementary chemotherapy.

Peptides with antioxidant properties identified from casein, whey, and egg albumin hydrolysates generated by two novel fungal proteases.

There are many diseases linked to oxidative stress, including cancer. Importantly, endogenous antioxidants are insufficient to protect against this process. Peptides derived from food proteins produced by hydrolysis have been investigated as exogenous antioxidants. The present study aimed to identify novel peptides with antioxidant potential produced from egg and milk proteins hydrolysis with two new fungal proteases isolated from Eupenicillium javanicum and Myceliophthora thermophila. The degree of hydrolysis at several time points was calculated and correlated to DPPH scavenging and metal chelating assays, all hydrolysates presented antioxidant activity. Casein hydrolyzed by the M. thermophila protease showed the best antioxidant activity. The identified sequences showed that the proportions of amino acids that influence antioxidant activity support the antioxidant assay. Our data reveal the conditions necessary for the successful generation of antioxidant peptides using two novel fungal proteases. This opens a potential new avenue for the design and manufacture of antioxidant molecules.

Analysis of the Specificity and Biochemical Characterization of Metalloproteases Isolated from Eupenicillium javanicum Using Fluorescence Resonance Energy Transfer Peptides.

Enzymes have important features that may facilitate their application in industrial processes and have been used as alternatives to chemical catalysts. In particular, proteases can be isolated from microorganisms, which provide important sources of advantageous enzymes for industrial processes. For example, Eupenicillium javanicum is a filamentous fungus that has been shown to express industrially applicable enzymes and chemical components, such as antifungal compounds. The biotechnological potential of E. javanicum and proteases made us search a novel protease from this microorganism. The macromolecule was isolated, the main biochemical properties was evaluated, and the specificity of the protease subsites was determined. The protease was produced under solid-state bioprocess with wheat bran and isolated by two chromatography steps with yield of 27.5% and 12.4-fold purification. The molecular mass was estimated at 30 kDa. The N-terminal sequence of the first 20 amino acid residues was AVGAGYNASVALALEKALNN. The enzyme presented higher proteolytic activity at pH 6.0 and 60°C. The protease is stable at wide range of pH values and temperatures and in the presence of surfactants. The "primed" side of the catalytic site showed the highest catalytic efficiency of the enzyme isolated from E. javanicum. The S'1 subsite is responsible for catalyzing the protease reaction with substrates with tyrosine in P'1. These findings provide important insights into the biochemical characterization of a highly active protease from E. javanicum and may facilitate the development of industrial processes involving this protease.

Determination of Specificity and Biochemical Characteristics of Neutral Protease Isolated from Myceliophthora thermophila.

Proteases hydrolyze polypeptides to release peptides and/or amino acids. This subclass of enzymes is among those with the most sales worldwide, particularly those produced by microorganisms. Proteases may be applied in the several industries, including the food industry, leather, detergents, and bioremediation. Myceliophthora thermophila protease was produced by a submerged bioprocess and then purified 185-fold by anion exchange and hydrophobic chromatography with a 37% yield. The molecular mass was estimated at 36.2 kDa, and mass spectrometry identified two sequences: GVVANMSLGGSYSASINNAAAALVR and STGNAAITGVPSGTTNR. The isolated protein was characterized biochemically, showed an optimum pH of 6.5 and optimum temperature of 45 °C, and stability at wide range of pH and temperatures and in the presence of reducing agents and some surfactants. Kinetic assays for this enzyme showed a greater catalytic efficiency when the substrate had alanine at position P'2. The protease presented characteristics that may be of interest to many industrial areas.

Acoustic neuroma observation associated with an increase in symptomatic tinnitus: results of the 2007-2008 Acoustic Neuroma Association survey.

OBJECT: Tinnitus is a known presenting symptom of acoustic neuromas, but little is known about the impact of observation or treatment on tinnitus. Most patients experience improvement with treatment, while others may worsen. Therefore, this study was designed to assess the overall impact of observation and treatment on tinnitus outcome in patients with acoustic tumors. METHODS: Data from the 2007-2008 Acoustic Neuroma Association survey were used. Tinnitus severity was graded both at presentation and at last follow-up for all patients questioned. This data set was analyzed using the Student t-test and a linear regression model adjusted for possible confounders. RESULTS: Overall there were more patients receiving intervention (n = 1138) for their acoustic neuromas than observation (n = 289). Presenting tumor size positively correlated with tinnitus severity score. Regardless of treatment (microsurgery or stereotactic radiosurgery), tinnitus improved at last follow-up and worsened in those who were observed (p = 0.02). When comparing microsurgical options, retrosigmoid and translabyrinthine resection improved tinnitus symptoms (both p < 0.01). Stereotactic radiosurgery had a treatment effect similar to microsurgery. CONCLUSIONS: Presenting tinnitus severity correlates strongly with tumor size. Furthermore, regardless of treatment, there appears to be an overall reduction in tinnitus severity for all forms of microsurgery and stereotactic radiosurgery. Importantly, observation leads to a worsening in symptomatic tinnitus and therefore should be weighed in the treatment recommendation.

Trends of lipoprotein variables from childhood to adulthood in offspring of parents with coronary heart disease: the Bogalusa Heart Study.

Although dyslipidemia among offspring of parents with coronary heart disease (CHD) has been known, the development of this adverse relationship with respect to specific lipoprotein variables from childhood to young adulthood has not been elucidated. This aspect was examined in a young adult cohort with (n = 271) and without (n = 805) a parental history of CHD followed longitudinally since childhood by repeated surveys from 1973 to 1991. Trends in fasting lipoprotein variables by parental CHD status were assessed by Lowess smoothing curve and Generalized Estimating Equations (GEE). In multivariate analyses adjusted for race and sex, parental CHD associated positively with low-density lipoprotein cholesterol (LDL-C, P <.01) and triglycerides (P <.05) mainly at the young adulthood age, whereas a positive association was noted with very-low-density lipoprotein cholesterol (VLDL-C) during both childhood and young adulthood (P <.05). The positive association between parental CHD and LDL-C in young adulthood persisted independently of body mass index (BMI) and fasting insulin, but disappeared when fasting glucose was added to the model. With respect to triglycerides and VLDL-C, inclusion of BMI, insulin, and/or glucose eliminated the adverse association with parental CHD. These observations suggest that parental CHD is just one more explanatory variable that loses its partial contribution to lipoprotein profiles in their offspring when other strongly interrelated contributory variables such as age, body fatness, and measures of glucose homeostasis are taken into account. Information on these risk variables in conjunction with parental or family history of CHD may enhance the potential of CHD risk assessment in youth.

Indications for immediate tissue transfer for soft tissue reconstruction in visceral pelvic surgery.

BACKGROUND: Perineal wound complications may occur after visceral pelvic surgery. We reviewed our experience to determine indications for immediate tissue transfer (TT) to prevent complications. METHODS: Hospital records and computerized data were reviewed on 175 perineal repairs in 156 patients treated at The University of Texas M.D. Anderson Cancer Center for tumors involving the alimentary tract (135 of 175), genitourinary tract (15 of 175), perineum (19 of 175), or sacrum (6 of 175). Patients had either resection of only the colorectum and anus (APR) (46 of 175) or multivisceral resection (MVR) (129 of 175), and the perineal wound was closed by using TT (108 of 175) or primary closure (PC) (67 of 175) on the basis of the surgeon's judgment. Complications were compared between PC and TT groups. RESULTS: Complications occurred in 57% (100 of 175). There was no significant difference overall in PC and TT procedures or in the APR subgroup. There were significantly fewer complications for TT patients in the MVR subgroup (P =.0001). There were significantly fewer complications for TT patients with prior irradiation in both APR (P =.01) and MVR (P =.007) subgroups. CONCLUSIONS: Immediate TT for perineal wound closure is associated with fewer healing complications than PC in a subset of patients with multivisceral resection or prior radiotherapy. Surgical planning in these cases should consider immediate soft tissue reconstruction.

Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic patients.

Elevation of glucose concentration in diabetes may induce generation of oxygen free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the present study was to investigate the effect of the oxidative stress on the activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic patients compared with the the control group. Blood aldose reductase activity was elevated in patients with type 2 diabetes compared with the control group. GSH was decreased while TBARS concentration was increased in red blood cells (RBC) and leukocytes from the patients with type 2 diabetes mellitus in comparison to the control group. The mean values of plasma LH, FSH and testosterone were decreased, whereas the mean plasma IGF-1 concentration was increased in type 2 diabetes compared with controls. These findings support the hypothesis that hyperglycemia enhances the activity of the polyol pathway and impairs the antioxidant status, particularly glutathione redox cycle, resulting in poorer defense against oxidative stress. In addition, decreased circulating testosterone and gonadotropin levels may reflect the oxidative stress exerted by diabetes.

Temporal relation between blood pressure and serum creatinine in young adults from a biracial community: the Bogalusa Heart Study.

It is well recognized that end-stage renal disease (ESRD) is associated with accelerated and malignant hypertension. The association of renal disease and what is considered as normal blood pressure is still not clear. The present study examined the temporal relation between blood pressure and renal function reflected by serum creatinine in a biracial (black-white) community-based population enrolled in the Bogalusa Heart Study. The study included 662 young adults aged 19 to 32 years, (white men, n = 188; white women, n = 289; black men, n = 67; and black women, n = 118) who were followed for an average of 7.4 years. In black men, partial correlation adjusted for age, body mass index, serum glucose, uric acid, and cigarette smoking showed that baseline systolic and diastolic blood pressure are not significantly related to baseline serum creatinine, but significantly related to serum creatinine at follow-up (r = 0.38, P = .008 and r = 0.42, P = .003, respectively). Multivariate regression analysis further showed a significant prediction of serum creatinine at follow-up by baseline systolic and diastolic blood pressure (0.031 mg/dL and 0.037 mg/dL rise in follow-up serum creatinine for every 10 mm Hg increase in systolic (P = .000) and diastolic (P = .001) blood pressure at baseline, but not the other way around. Other race and sex groups did not show such significant temporal relations. We conclude that in young black men, higher blood pressure levels within normal range precede and explain part of the increase in serum creatinine, a measure of decline in renal function. Thus, our results underscore the beneficial effect of maintaining blood pressure levels lower than what is considered as the upper normal limit, particularly in black men.

Screening sonohysterography in infertility.

This prospective comparative study was carried out to assess the value of sonohysterography (SHG) in evaluating both the endometrial cavity and tubal patency in infertile patients and to compare its results with hysterosalpingography (HSG), diagnostic hysteroscopy and laparoscopic chromopertubation. It comprised 84 infertile women who were examined using SHG the day before combined diagnostic laparoscopy and hysteroscopy. Eighty-three patients had had HSG within 6 months. As regards the appearance of the endometrial cavity, the results of SHG agreed with hysteroscopy in 72.2% (k = 0.31) while HSG agreed with hysteroscopy in 75.6% (k = 0.39) of cases. The appearance of the right and left tubes using SHG agreed with laparoscopy in 72.4% (k = 0.16) and 60.5% (k = 0.13), respectively, while HSG agreed with laparoscopy in 94% (k = 0.52) and 90.4% (k = 0. 51), respectively. However, when the appearance of fluid in DP was considered as an indirect indicator of patency of at least one tube at SHG, the agreement with laparoscopy rised to 88.1% (k = 0.24) and 85.7% (k = 0.18) for both tubes respectively. In conclusion, SHG is similar to HSG as regards the appearance of the endometrial cavity but it is inferior to it for evaluating tubal factor. The implication of SHG in the infertility work-up as a simple and fast procedure can minimize costs and abuses of sophisticated techniques particularly in the developing countries with limited resources.

Simplified biophysical profile: an antepartum fetal screening test.

A total of 330 high-risk pregnant women with gestational ages of 32-42 weeks were followed until delivery using the biophysical profile (BPP) and a screening test consisting of the amniotic fluid index together with fetal acoustic stimulation under ultrasound M-mode scanning. The test was compared with the BPP and nonstress test (NST) for predicting abnormal outcome. The sensitivities of the BPP, NST and the proposed test were 100, 98.4 and 100%, respectively, the negative predictive values were 100, 99.4 and 100%, while the false-positive rates were 21.3, 39.3 and 67%. Our simplified biophysical testing method is suggested to be a good negative preliminary screening test, while positive results require further fetal testing methods. This test reduced the need for BPP in many high-risk patients and had the advantages of simplicity, low cost and less time consumption.

Fetal biophysical activities in third-trimester pregnancies complicated by diabetes mellitus.

OBJECTIVE: Our purpose was to compare third-trimester fetal biophysical activities in normal and well-controlled insulin-dependent diabetic pregnancies. STUDY DESIGN: We performed serial bimonthly fetal biophysical studies from 30 to 38 weeks in 18 normal and 18 well-controlled insulin-dependent diabetic pregnancies (White classes B through D). Each study contained 60 minutes of simultaneous ultrasonographic recordings of fetal breathing movements and rates, baseline heart rate, and body movements. Mean daily blood glucose levels of diabetic patients were determined from home monitors; HbA1c was determined every 6 weeks and ultrasonographic fetal growth rates every 3 weeks. Data were compared with t tests, analysis of variance with repeated measures, and chi 2 tests. RESULTS: Women in the diabetic group maintained good glycemic control and were delivered of normal infants of weights similar to those of nondiabetic gravidas. Their fetuses had higher mean incidences of fetal breathing movement, fetal heart rates, and fetal breathing rates but lower fetal movements and fetal heart rate acceleration counts than did controls throughout the study. Neither short- nor long-term maternal glycemic levels correlated well with fetal biophysical performance. CONCLUSIONS: In spite of good maternal glycemic control fetuses of diabetic women behaved differently from those of nondiabetic women. Modulation of their biophysical activities may be affected by maternal glycemic status before the last trimester. Different standards might need to be applied to interpret their tests.

Superiority of amniotic fluid index over amniotic fluid pocket measurement for predicting bad fetal outcome.

Semiquantitative amniotic fluid volume (AFV) determination is a component of the fetal biophysical profile (BPP). To assess decreased AVF we did BPPs of 174 fetuses within 1 week of delivery. Two methods were used: measurement of the single largest vertical pocket (oligohydramnios = depth < 1 cm) and the four-quadrant amniotic fluid index (AFI) (oligohydramnios = AFI < or = 5 cm). AFV, as determined by each method, was related to measures of fetal outcome (perinatal mortality, fetal distress, Apgar score, meconium-stained amniotic fluid, and intrauterine growth retardation [IUGR]). The AFI was more sensitive in predicting mortality (87.5%) and the following measures of perinatal morbidity: low 5-minute Apgar score (88.8%), fetal distress during labor (86.6%), meconium-stained amniotic fluid (63.6%), and the presence of IUGR (79.4%). The sensitivity of amniotic fluid pocket measurement of < 1 cm was 75%, 72.2%, 66.6%, 47.7%, and 55.8%, respectively, for the same measures. Using the AFI instead of a single pocket measurement in BPP assessment increased the sensitivity and positive predictive value of the BPP from 64.7% to 76.4% and from 45.8% to 68.4%, respectively. Our data suggest that qualitative AFV measurement using the AFI is superior to that of the single largest pocket in multiple component fetal biophysical testing.

The prediction of "controlled" uterine rupture by the use of intrauterine pressure catheters.

OBJECTIVE: To determine whether uterine activity, assessed by either fluid-filled or solid pressure catheters, changes with uterine incision at cesarean delivery. METHODS: Uterine activity was recorded continuously during low transverse cesarean delivery in ten parturients using fluid-filled pressure catheters and in ten women with solid pressure catheters. Visual analyses were performed of the last 30 minutes of uterine recording before uterine incision and of the period after incision; the analyses were then compared within and between the catheter groups for mean uterine tone and contraction amplitude, frequency, and duration. Oxytocin use, anesthesia method, mean gestational age, birth weight, length of labor, duration of monitoring, and uterine incision-to-delivery time were compared between the groups. RESULTS: All obstetric end points were similar in both catheter groups except for a higher mean birth weight in the solid-catheter group. The mean (+/- standard deviation) duration of post-incision monitoring was 4.7 +/- 0.94 minutes. After uterine incision, mean tone and contraction amplitude were unchanged, whereas mean contraction frequency and duration decreased significantly. CONCLUSIONS: Though intrauterine monitoring was brief, this model allows a unique view of "controlled" uterine rupture. Spontaneous uterine rupture may evolve more gradually; however, neither catheter type would be likely to aid its early recognition.

Refining the biophysical profile with a risk-related evaluation of test performance.

OBJECTIVE: Our objective was to determine the ability of biophysical profile variables to predict bad perinatal outcome in high-risk third-trimester pregnancy. STUDY DESIGN: The outcomes of 1146 fetuses were correlated with abnormal single or multiple variables occurring in biophysical profile done within 72 hours of delivery. Theoretic risks of poor outcomes for different combinations of abnormal variables, calculated with Shortlife's formula, were compared with the actual risks observed (chi 2 tests). RESULTS: Two hundred forty-six fetuses had at least one abnormal biophysical profile variable with the risk of bad outcome, for a single abnormal variable, ranging from 8% (body movements) to 100% (tone) and increasing from 14% (any variable abnormal) to 63% (all variables abnormal). In most (57%) observed combinations of biophysical profile variables, significant differences between theoretic and actual risks of bad outcomes were found. By stepwise logistic regression the best predictive model contained all variables except fetal movement. CONCLUSIONS: Dynamic biophysical profile variables appear to be interdependent. Not all combinations of abnormal variables occur and specific combinations improve prediction of poor outcome. Risk-related scales for biophysical profile outcomes might prove superior to more conventional scoring systems.

Leucocyte superoxide dismutase in rheumatoid arthritis.

Superoxide dismutase (SOD) activity was measured in polymorphonuclear leucocytes (PMNLs) and mononuclear cells (MNCs) from 60 patients with rheumatoid arthritis (RA) and in 15 controls. In all patients and controls SOD activity (U/mg protein) in MNCs was twice that in PMNLs. SOD activity in PMNLs and in MNCs from patients with RA was significantly higher than that in controls. SOD activity in PMNLs (but not in MNCs) from patients treated with corticosteroids was significantly higher than that from patients treated with nonsteroidal anti-inflammatory drugs. There was no relation between SOD activity in both PMNLs and MNCs and either the patients' age, sex, duration of disease, serum immunoglobulin concentration, IgM rheumatoid factor, and copper level, or the degree of disease activity.