Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1-23.4) vs 6.2 (0-17) vs 3.3 (0-14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Herpes zoster infection in childhood-onset systemic lupus erythematosus patients: a large multicenter study.

OBJECTIVE: The aim of this multicenter study in a large childhood-onset systemic lupus erythematosus (cSLE) population was to assess the herpes zoster infection (HZI) prevalence, demographic data, clinical manifestations, laboratory findings, treatment, and outcome. METHODS: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in ten Pediatric Rheumatology services in São Paulo State, Brazil, and included 852 cSLE patients. HZI was defined according to the presence of acute vesicular-bullous lesions on erythematous/edematous base, in a dermatomal distribution. Post-herpetic neuralgia was defined as persistent pain after one month of resolution of lesions in the same dermatome. Patients were divided in two groups for the assessment of current lupus manifestations, laboratory findings, and treatment: patients with HZI (evaluated at the first HZI) and patients without HZI (evaluated at the last visit). RESULTS: The frequency of HZI in cSLE patients was 120/852 (14%). Hospitalization occurred in 73 (61%) and overlap bacterial infection in 16 (13%). Intravenous or oral aciclovir was administered in 113/120 (94%) cSLE patients at HZI diagnosis. None of them had ophthalmic complication or death. Post-herpetic neuralgia occurred in 6/120 (5%). After Holm-Bonferroni correction for multiple comparisons, disease duration (1.58 vs 4.41 years, p < 0.0001) was significantly lower in HZI cSLE patients compared to those without HZI. Nephritis (37% vs 18%, p < 0.0001), lymphopenia (32% vs 17%, p < 0.0001) prednisone (97% vs 77%, p < 0.0001), cyclophosphamide (20% vs 5%, p < 0.0001) and SLE Disease Activity Index 2000 (6.0 (0-35) vs 2 (0-45), p < 0.0001) were significantly higher in the former group. The logistic regression model showed that four independent variables were associated with HZI: disease duration < 1 year (OR 2.893 (CI 1.821-4.597), p < 0.0001), lymphopenia <1500/mm(3) (OR 1.931 (CI 1.183-3.153), p = 0.009), prednisone (OR 6.723 (CI 2.072-21.815), p = 0.002), and cyclophosphamide use (OR 4.060 (CI 2.174-7.583), p < 0.0001). CONCLUSION: HZI is an early viral infection in cSLE with a typical dermatomal distribution. Lymphopenia and immunosuppressive treatment seem to be major factors underlying this complication in spite of a benign course.

A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases.

OBJECTIVE: To describe onset features, classification and treatment of juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) from a multicentre registry. METHODS: Inclusion criteria were onset age lower than 18 years and a diagnosis of any idiopathic inflammatory myopathy (IIM) by attending physician. Bohan & Peter (1975) criteria categorisation was established by a scoring algorithm to define JDM and JPM based on clinical protocol data. RESULTS: Of the 189 cases included, 178 were classified as JDM, 9 as JPM (19.8: 1) and 2 did not fit the criteria; 6.9% had features of chronic arthritis and connective tissue disease overlap. Diagnosis classification agreement occurred in 66.1%. Median onset age was 7 years, median follow-up duration was 3.6 years. Malignancy was described in 2 (1.1%) cases. Muscle weakness occurred in 95.8%; heliotrope rash 83.5%; Gottron plaques 83.1%; 92% had at least one abnormal muscle enzyme result. Muscle biopsy performed in 74.6% was abnormal in 91.5% and electromyogram performed in 39.2% resulted abnormal in 93.2%. Logistic regression analysis was done in 66 cases with all parameters assessed and only aldolase resulted significant, as independent variable for definite JDM (OR=5.4, 95%CI 1.2-24.4, p=0.03). Regarding treatment, 97.9% received steroids; 72% had in addition at least one: methotrexate (75.7%), hydroxychloroquine (64.7%), cyclosporine A (20.6%), IV immunoglobulin (20.6%), azathioprine (10.3%) or cyclophosphamide (9.6%). In this series 24.3% developed calcinosis and mortality rate was 4.2%. CONCLUSION: Evaluation of predefined criteria set for a valid diagnosis indicated aldolase as the most important parameter associated with definite JDM category. In practice, prednisone-methotrexate combination was the most indicated treatment.

Rapid test for the evaluation of the activity of the prodrug hydroxymethylnitrofurazone in the processing of Trypanosoma cruzi messenger RNAs.

No fully effective treatment has been developed since the discovery of Chagas' disease by Carlos Chagas in 1909. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effectiveness in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Many natural and/or synthetic substances showing trypanocidal activity have been used, even though they are not likely to be turned into clinically approved drugs. Originally, drug screening was performed using natural products, with only limited knowledge of the molecular mechanism involved in the development of diseases. Trans-splicing, which is unusual RNA processing reaction and occurs in nematodes and trypanosomes, implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. In the present study, permeable cells of T. cruzi epimastigote forms (Y, BOL and NCS strains) were treated to evaluate the interference of two drugs (hydroxymethylnitrofurazone - NFOH-121 and nitrofurazone) in the trans-splicing reaction using silver-stained PAGE analysis. Both drugs induced a significant reduction in RNA processing at concentrations from 5 to 12.5 microM. These data agreed with the biological findings, since the number of parasites decreased, especially with NFOH-121. This proposed methodology allows a rapid and cost-effective screening strategy for detecting drug interference in the trans-splicing mechanism of T. cruzi.

Detection of p53 gene mutations in human esophageal squamous cell carcinomas using a p53 yeast functional assay: possible difference in esophageal carcinogenesis between the young and the elderly group.

A p53 yeast functional assay, which cannot only detect p53 gene mutations but also can assess p53 gene function, was used to screen for p53 gene dysfunction in human esophageal squamous cell carcinomas. Surgically resected frozen tissues of esophageal squamous cell carcinomas from 57 patients were examined for p53 gene mutation. Because the mean age of the patients diagnosed with esophageal squamous cell carcinoma was 64 years, we classified those who were <65 years of age as the Young Group and classified the others as the Elderly Group. The incidence of p53 gene mutations was 43 of 57 (75%). The incidence of p53 gene mutations observed in the Young Group was significantly higher than in the Elderly Group (P = 0.0007). Alcohol and smoking status did not relate to p53 gene mutation expression. Survival rate after surgery was not significantly associated with the presence of p53 gene mutation. However, in the Young Group with p53 gene mutation, those who had null mutations had a significantly shorter survival than those without null mutations (P = 0.0455). No other clinicopathological factors were associated with p53 gene mutations. Possibly, there may be a difference in esophageal carcinogenesis between the Young and the Elderly groups, because the incidence of p53 gene mutations is different between the two groups. In the Young Group, p53 gene mutation may cause esophageal carcinogenesis, and null mutation for p53 gene is a significant prognostic factor.

Evaluation of ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, with a PGD2-responsive cell line from bovine embryonic trachea.

ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (cyclic AMP) level in EBTr cells dose-dependently, being more than 100 fold over the basal level at 1 microM. The half-maximally effective concentration of PGD2 or ZK110841 was 10-30 nM. Increasing concentrations (10(-7)-10(-4) M) of AH6809 (which possesses negligible intrinsic agonist activity) produced parallel shifts to the right of dose-response curves to PGD2 and ZK110841. Schild plots of these data were linear (correlation close to unity) and pA2 values against PGD2 and ZK110841 were calculated to be 6.36 and 6.57, respectively, indicating that AH6809 is a simple and competitive antagonist. These results demonstrate that ZK110841, AH6809 and EBTr cells will be useful for characterization of DP-receptors.

Surgical reconstruction of an ascending aortic dissection in Takayasu's arteritis.

A 45-year-old Japanese woman with Stanford type A dissecting aortic aneurysm underwent a reconstructive operation on the ascending aorta. Histopathological diagnosis was Takayasu's arteritis in the chronic and inactive phase. It is very rare that a dissecting aortic aneurysm results from Takayasu's arteritis. Long-standing hypertension and fragility of the aortic media due to disruption of elastic fibers were suspected to cause dissection in the entire aorta in this case.

Structure-physicochemical function relationships of soybean beta-conglycinin constituent subunits.

Beta-conglycinin, one of the dominant storage proteins of soybean, has a trimeric structure, being composed of three subunits alpha, alpha', and beta. The alpha and alpha' subunits contain the extension regions in addition to the core regions common to all subunits, which are N-glycosylated. Physicochemical functions of recombinant nonglycosylated individual subunits and deletion mutants (alpha(c) and alpha'(c)) lacking the extension regions of the alpha and alpha' subunits were examined at pH 7.6 and 3.7 at low (mu = 0.08) and high (mu = 0.5) ionic strengths. Although individual recombinant subunits exhibited different properties at all conditions, there were some consistencies. Surface hydrophobicities and thermal stabilities of the individual subunits were likely to be conferred by their core regions, and the carbohydrate moieties did not contribute to these properties at any conditions examined here. Solubility at mu = 0.08, heat-induced association, and emulsifying ability remarkably depended on the extension regions and the carbohydrate moieties in addition to the structural features of the core regions. These findings indicate that various end products could be produced by the selection of soybean varieties containing beta-conglycinin with different subunit compositions and suggest a direction for a principle of soybean breeding.

Collagenous fibroma (desmoplastic fibroblastoma) of the palate: a case report.

Collagenous fibroma is an uncommon benign soft tissue lesion that has a wide anatomic distribution. We describe a case of a collagenous fibroma that appeared in the left soft and hard palate of a 37-year-old woman as a 5.0-cm solitary, firm nodule. Microscopically, it was composed of stellate or spindle-shaped cells embedded in hypovascular fibrous stroma. Entrapment of fat was focally identified at the edges. Mitotic figures and tumor necrosis were absent. Tumor cells were immunopositive for vimentin, and a few cells were positive for alpha-smooth muscle actin. Tumor extracellular matrix was immunopositive for type I and type III collagen, as well as for fibronectin. These findings satisfied the diagnostic criteria for collagenous fibroma (desmoplastic fibroblastoma). This case, to our knowledge, represents the first report of this tumor in the mouth. The differential diagnosis of fibrous lesions of the mouth is discussed.

[Clinical significance of ambulatory intraesophageal bilirubin monitoring in diagnosis of gastroesophageal reflux].

To evaluate the usefulness of ambulatory intraesophageal bilirubin monitoring in the diagnosis of GER, 38 patients with reflux symptoms and 7 controls were studied, using Bilitec 2000. The % time of bilirubin and acid reflux was less than 5% in all of the controls. In 3 patients of NUD, % time of acid reflux was less than 5%, but that of bilirubin was more than 8% in 2 patients. Acid reflux was found only in 1 of 4 patients who had a history of subtotal gastrectomy, but abnormal bilirubin reflux was found in all of 4 patients. In the other 31 patients, a significant difference was found in the % time of bilirubin reflux by the severity of reflux esophagitis, whereas this difference was not found in that of acid reflux. Intraesophageal bilirubin monitoring is useful in the diagnosis of GER and is essential in patients with hypochlorhydria or minimal reflux.

[Cardiac arrest episodes by cardiomyopathy following total pancreatectomy, a case report].

A 47-year-old man with advanced pancreatic carcinoma underwent total pancreatectomy with resection of the involved portal vein. His postoperative course was complicated by a couple of cardiac arrest episodes. The first episode occurred seven weeks after surgery during drip infusion of CDDP, and later on during the thirteenth week after surgery. There was no apparent cause for those episodes. On both occasions resuscitation was performed adequately. The second arrest was followed by deep inverted T waves on ECG, however, not by elevation of serum CPK-MB. Because of this, myocardial infarction was ruled out. The diagnosis of cardiomyopathy was made possible through the discovery on the echocardiogram of a hypertrophied left ventricle with thick interventricular septum. Then, on catheterization, myocardial squeezing in the left anterior descending coronary artery was noticed. Finally, histological findings concerning the biopsied cardiac muscle led to the same diagnosis. Cardiac arrest in this case seemed to be due to arrhythmia caused by cardiomyopathy. Echo cardiography should be routinely used as part of the examination prior to extended major surgery.

High numerical aperture planar microlens with swelled structure.

The planar microlens is a 2-D integrated microlens fabricated by the selective ion exchange technique. This paper demonstrates a new class of planar microlens which has a high numerical aperture. The new planar microlens uses a swelling structure and index distribution which comes from replacing ions with different ion volumes. Lens diameters from 10 to 400 microm can be fabricated. A numerical aperture larger than 0.5 is achieved when the lens diameter is smaller than 100 microm. Use of this microlens in light coupling between an LD and a single-mode fiber is also evaluated.

Granulocyte superoxide anion and elastase release during cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is known to induce several pathogenic responses in cardiovascular surgery. To explore leukocyte activation during PCB, we investigated superoxide anion (O2-) production by granulocytes in 6 patients undergoing aortocoronary bypass surgery. O2- production was determined with chemiluminescence amplified by a cypridina luciferin analogue. Granulocytes collected from the blood in the arterial site of the CPB circuit were stimulated by phorbol myristate acetate, n-formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan. All the stimulators failed to disclose a significant difference between the magnitude of chemiluminescence during and after CPB. However, significant complement activation was detected, and the plasma level of granulocyte elastase increased gradually during and after CPB. This discrepancy between the unchanged O2- production by stimulated granulocytes and the increase in inflammatory mediators including granulocyte elastase may be due to sequestration of activated granulocytes in extravascular tissues. Namely, it was highly likely that activated granulocytes responsible for the increased plasma elastase level were sequestered and remained outside the blood circulation.

[Effects of superoxide dismutase administered by coronary sinus retroperfusion on ischemic reperfused canine heart].

The efficacy of superoxide dismutase administered using synchronized coronary venous retroperfusion (SRP) on the extent of myocardial reperfusion injury was studied. Eighteen mongrel dogs were divided into three groups. A control group (group A) consisting of six dogs was subjected to 90 minutes of acute myocardial ischemia via balloon occlusion of the left anterior descending coronary artery (LAD) followed by 6 hours of reperfusion following abrupt deflation of the balloon. In the second group (group B) consisting of six dogs, the LAD was occluded for 2 hours followed by 5.5 hours of reperfusion. In this group, SRP was applied for 30 minutes prior to full reperfusion. In the third group (group C) consisting of six dogs, balloon inflation and deflation was performed in the same manner as group B except the administration of 10 mg/kg of superoxide dismutase (SOD) using SRP. During the occlusion of LAD, severe ischemia was detected by blood flow measurement using color microsphere in all groups. After reperfusion regional blood flow expressed as the percent of preocclusion value in the subendocardial area in three groups were 25% (group A), 38% (group B) and 76% (group C), respectively. There were significant differences between the groups (p < 0.05). Left ventricular function was assessed as global ejection fraction. Although occlusion of the LAD resulted in a reduction of the left ventricular ejection fraction with a similar magnitude in all groups (A; 37 +/- 5%, B; 32 +/- 7%, C; 58 +/- 10%), there was an improvement in groups B and C during reperfusion (p < 0.05). Infarct size was assessed by triphenyl tetrazolium chloride staining.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical repair of vascular ring with aberrant brachiocephalic artery].

The vascular ring causes tracheal and esophageal compression and some cases need the surgical intervention. We report a rare case of vascular ring with aberrant brachiocephalic artery. A nine-month-old boy had suffered from progressing stridor and was admitted to our hospital due to the stridor. The digital subtraction angiography revealed the aberrant brachiocephalic artery which compressed the trachea from anterior aspect. The compression of the trachea was released by tacking forward the aberrant brachiocephalic artery to the sternum with the aid of two stitches. The postoperative course was uneventful. The stridor almost disappeared at one year after the operation.

Multiple imaging and multiple Fourier transformation using planar microlens arrays.

A new type of multiple imaging and multiple Fourier transformation system under coherent illumination using microlens arrays has been developed. The optical system is based on geometrical optics instead of convolution or diffraction. As a result, it has the advantage of design flexibility especially in alignment of the duplicate images. The experimental results of the system, which are implemented using planar microlens arrays fabricated by an ion exchange technique, are also discussed.

Identification of a GPI-anchored type HDL-binding protein on human macrophages.

To identify the HDL3-binding proteins on human macrophages, we examined the involvement of GPI-anchored protein in the binding of HDL3, and tried to purify HDL3-binding protein. From membrane fractions of macrophages, we obtained 80- and 130-kDa HDL3-binding proteins by ligand blotting. Treatment of macrophages with phosphatidylinositol-specific phospholipase C (PI-PLC) significantly decreased the specific HDL3-binding in a dose-dependent manner. Furthermore, treatment with mannosamine, which blocks GPI-anchor formation, decreased specific HDL3-binding in a dose-dependent manner. PI-PLC treatment released from the cells the proteins with an M(r) of 80 kDa, which could also bind HDL3. PI-PLC as well as mannosamine treatment markedly reduced cholesterol efflux from macrophages in association with the decreased HDL-binding. Using HDL3-affinity chromatography, we purified 80-kDa GPI-anchored type HDL3-binding protein. In summary, we demonstrate the implication of 80-kDa GPI-anchored protein in the binding of HDL3 to human macrophages, which might have some role in reverse cholesterol transport.

The roles of the N-linked glycans and extension regions of soybean beta-conglycinin in folding, assembly and structural features.

Beta-conglycinin, one of the dominant storage proteins of soybean, is a trimer composed of three subunits, alpha, alpha' and beta. All subunits are N-glycosylated and alpha and alpha' contain extension regions in addition to the core regions common to all subunits. Non-glycosylated individual subunits and deletion mutants (alpha(c) and alpha'(c)) lacking the extension regions of alpha and alpha' were expressed in Escherichia coli. All recombinant proteins were purified to near homogeneity and appeared to have the correct conformation, as judged by CD, density-gradient centrifugation and gel-filtration profiles, indicating that the N-linked glycans and extension regions are not essential for the folding and the assembly into trimers of beta-conglycinin. Density-gradient centrifugation, gel-filtration and differential scanning calorimetry profiles of the recombinant proteins and the native beta-conglycinin indicated that the N-linked glycans and extension regions contribute to the dimension of beta-conglycinin but not to the density and the thermal stability. Comparing the solubilities of the individual subunits with those of deletion mutants, only the alpha and alpha' subunits were soluble at lower ionic strength (mu < 0.25) at around the pH value of the endoplasmic reticulum. This suggests that the extension regions play an important role in the prevention of aggregation in the endoplasmic reticulum in analogy with the N-linked glycans.