Comparing the 1997 update of the 1982 American College of Rheumatology (ACR-97) and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria for systemic lupus erythematosus (SLE) classification: which enables earlier classification of SLE in an urban Asian population?

OBJECTIVE: We compared the 1997 update of the 1982 American College of Rheumatology (ACR-97) and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria, for earlier classification of systemic lupus erythematosus (SLE) in a multiethnic urban Asian SLE population. METHODS: Patients from a retrospective, nested case-control study of the influence of lupus nephritis on mortality in SLE were studied. For each patient, dates of first manifestations of each criteria (both ACR-97 and SLICC-12) were recorded, and the date of disease classification using ACR-97 or SLICC-12 criteria was compared to determine which criteria resulted in earlier classification. RESULTS: Among 182 SLE patients (74.2% Chinese, 18.1% Malay, 4.4% Indian and 3.3% Other ethnicities), 10 (5.5%) did not fulfill the ACR-97 criteria and 2 (1.1%) did not fulfill the SLICC-12 criteria. Using the SLICC-12 criteria, 18% of subjects showed earlier classification, whereas 7% of subjects showed earlier classification using the ACR-97 criteria. The SLICC hematologic criteria of "Leukopenia or lymphopenia" contributed most significantly to earlier diagnosis by SLICC-12. "Leukopenia or lymphopenia'' was present in 59% (19/32) of patients where SLICC-12 criteria allowed for earlier classification than ACR-97, compared with 15.4% (2/13) of patients where ACR-97 allowed earlier classification than SLICC-12 ( p = 0.02). The immunologic criterion that is considered a strength of the SLICC-12 criteria did not appear to contribute significantly to earlier diagnosis in this study. CONCLUSION: SLICC-12 criteria allow for earlier classification of SLE in a multiethnic cohort of Asian patients, supporting the validity of the SLICC-12 criteria and its use in clinical care and research.

Isometric force development, isotonic shortening, and elasticity measurements from Ca2+-activated ventricular muscle of the guinea pig.

Isometric tension and isotonic shortening were measured at constant levels of calcium activation of varying magnitude in mechanically disrupted EGTA-treated ventricular bundles from guinea pigs. The results were as follows: (a) The effect of creatine phosphate (CP) on peak tension and rate of shortening saturated at a CP concentration more than 10 mM; below that level tension was increased and shortening velocity decreased. We interpreted this to mean that CP above 10 mM was sufficient to buffer MgATP(2-) intracellularly. (b) The activated bundles exhibited an exponential stress-strain relationship and the series elastic properties did not vary appreciably with degree of activation or creatine phosphate level. (c) At a muscle length 20 percent beyond just taut, peak tension increased with Ca(2+) concentration over the range slightly below 10(-6) to slightly above 10(-4)M. (d) By releasing the muscle length-active tension curves were constructed. Force declined to 20 percent peak tension with a decrease in muscle length (after the recoil) of only 11 percent at 10(-4)M Ca(2+) and 6 percent at 4x10(-6)M Ca(2+). (e) The rate of shortening after a release was greater at lower loads. At identical loads (relative to maximum force at a given Ca(2+) level), velocity at a given time after the release was less at lower Ca(2+) concentrations; at 10 M(-5), velocity was 72 percent of that at 10(-4)M, and at 4x10(-6)M, active shortening was usually delayed and was 40 percent of the velocity at 10(-4) M. Thus, under the conditions of these experiments, both velocity and peak tension depend on the level of Ca(2+) activation over a similar range of Ca(2+) concentration.

Correlated effects of cigarette smoke components on alveolar macrophage adenosine triphosphatase activity and phagocytosis.

An initial examination was made of the hypothesis that one action of cigarette smoke components on pulmonary alveolar macrophage function involves the inhibition of contractile protein adenosine triphosphatase activity. Pulmonary alveolar macrophage calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, sodium-potassium-dependent adenosine triphosphatase activity, phagocytosis, and cell adhesiveness were measured in the presence of cigarette smoke, acrolein, ouabain, and ethacrynic acid. Calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, phagocytosis, and adhesiveness were inhibited by smoke and ethacrynic acid, but not by ouabain. Acrolein, a component of smoke, inhibited phagocytosis, adhesiveness, and calcium-dependent adenosine triphosphatase activity, indicating that another component of smoke must be effective at inhibiting magnesium-dependent adenosine triphosphatase activity. Sodium-potassium-dependent adenosine triphosphatase activity was inhibited by ouabain and ethacrynic acid, but not by smoke or acrolein. Finally, sulfhydryl reagents at least partially protected the macrophages against the inhibitory actions of each of the agents. The results are in accord with recently obtained experimental evidence that calcium-dependent adenosine triphosphatase and, perhaps, magnesium-dependent adenosine triphosphatase play a role in phagocytosis. The data also suggest that smoke components affect a number of macrophage activities, including adhesion and phagocytosis, by altering the cell's contractile apparatus.

Changes in collagen and elastin in rabbit right-ventricular pressure overload.

Collagen content, the ratio of collagen types I and III and elastin content were measured in 5-6- and 10-12-week-old rabbits with and without right-ventricular pressure overload. Significant and equivalent hypertrophy occurred in both age groups. A 2-day pressure overload caused a fall in collagen concentration below control levels in right-ventricular tissue from the older animals, but no change in the younger ones. A 2-week pressure overload in the older animals resulted in a rise in collagen concentration, a decreased ratio of type III to type I plus III [III/(I + III)] collagens, a fall in desmosine concentration and a fall in the desmosine/hydroxyproline ratio in the right ventricle. None of these changes occurred in the younger age group. We hypothesize that the changes in connective-tissue proteins after overload in the older group may contribute to previously observed changes in mechanical performance. The divergent connective-tissue responses in the two groups suggest the importance of age in determining outcome, as well as the possibility of separate regulatory mechanisms for contractile and for architectural elements of the heart.

Effect of phalloidin on liver actin distribution, content, and turnover.

Phalloidin increases F-actin microfilament content and actin-directed immunofluorescence in hepatocytes in vivo and also increases actin polymerization and the stability of F-actin in vitro. We studied the sensitivity of immunofluorescent staining of actin to an actin depolymerizing factor (ADF) as well as actin content, degree of polymerization, and turnover in livers of in vivo phalloidin-treated rats. Pretreatment with ADF abolished anti-actin antibody (AAA) staining of normal liver but did not modify staining of livers from phalloidin-treated animals. Planimetric analyses of SDS-polyacrylamide gels showed the percent actin of total protein was increased by approximately 40% and the absolute amount of actin by approximately 43%, ten days after daily phalloidin treatment (50 micrograms/100 gm body weight). Similar but smaller changes could be seen after one day of treatment. Ultracentrifugational analyses of liver extracts indicated no change in the amount or proportion of G-actin but a 194% increase in the proportion of F-actin in ten-day treated animals, changes also apparent in one day animals. Neither the relative fractional rate of actin synthesis nor its synthesis as a percent of total protein synthesis was altered either at one-day or ten-day post-phalloidin treatment. Dualisotope experiments indicated that the rate of actin degradation was decreased selectively in the one- to three-day period following drug treatment. Thus, phalloidin appears to stabilize actin against the depolymerizing actions of ADF, increases the proportion of F-actin without altering the size of the G-actin pool, and causes accumulation of actin by decreasing its relative rate of degradation.

Age dependence of smooth muscle myosin expression by cultured rat aortic smooth muscle cells.

Vascular smooth muscle cells (SMC) in vivo are highly heterogeneous phenotypically, particularly during development and in the adult during periods of remodeling. Much remains to be learned, however, regarding regulation of the SMC phenotype at the gene level. Here, we studied smooth muscle myosin heavy chain (SMMHC) expression at the transcriptional and mRNA levels in SMC cultured from newborn, adult, and old animals, which express different patterns of differentiation markers. We also examined regulation of SMMHC gene expression by TGF-beta, a cytokine known to be involved in the differentiation process. The activity of SMMHC promoter constructs, the expression of which is smooth-muscle-specific, was greatest in SMC from newborn animals and least in cells from old animals. Thus, differences in the degree of differentiation of SMC from these three sources may at least in part be due to transcriptional events. SMC from the three animal sources each contained mRNAs for the SM-1A and SM-2A tail but not those for the SM-1B and SM-2B head isoforms. Total SMMHC mRNA levels reflected similar differences as found at the transcriptional level. SM-2A mRNA as a proportion of total SMMHC mRNA was greatest in SMC from newborn animals, consistent with their higher degree of differentiation. TGF-beta up-regulated both transcription and mRNA levels but did not change the proportions of SMMHC mRNAs. Though the levels of transcriptional activity and mRNA were widely different in untreated cells, the degree of TGF-beta stimulation was approximately the same in all cases.