Peptides from Vh regions of antibodies to DNA activate T cell help to upregulate autoantibody synthesis

A model is a mathematical representation of a system that can be used to explore the system in a number of ways: to determine the system's internal connections, to calculate properties of the system such as flow rates and pool sizes, and to make predictions about the system's behavior under different conditions. The use of modeling to explore whole-body metabolism is demonstrated using a compartmental model of zinc kinetics as an example. Because models are useful tools for exploring systems, a facility called a "model library" is being established on the Internet to provide access to working versions of published models.     

Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo

The purpose of this study was to identify the optimal knot construction for interrupted dermal sutures. A synthetic braided absorbable suture, sizes 3-0 and 5-0, was selected for this evaluation. With reproducible mechanical performance tests, we determined that the construction of secure knots without ears required one additional throw as compared with secure knots with 3-mm ears. The direction of applied tension did not alter knot security, with the exception of granny knots, which required an extra throw when tension was applied parallel to the suture loop. Because interrupted dermal knot construction is accomplished without knot ears and with an applied tension parallel to the wound, one additional throw must be added to the knot to ensure knot security.     

Microcephaly with chorioretinopathy. A report of two dominant families and three sporadic cases

This study was designed to assess the effect of paraquat on the rat kidney. The experimental animals used were Wistar rats, a strain selected and maintained at the Institut d'hygiène alimentaire. Their diet was well defined and their state of health monitored. Female animals with mean weight of 200 g were used in this study. Doses of 20, 30 and 50 mg/kg were administered via the gastrointestinal route. In this experimentation, performed on 12 rats plus 3 controls, the dose considered to be sublethal was 30 mg/kg administered by gavage. These animals were sacrificed after 24 h, 48 h, 4, 8, 15, 30 and 60 day, selecting those animals with the most severely altered state, at each time. Tubular lesions started to appear by the 24th hour; the proximal tubule was the most sensitive. Lesions of the distal tubule were observed slightly later, from the 48th hour. Lesions became more intense from the 4th day onwards and reached a maximum on the 8th day. The first signs of repair of the proximal tubule and distal tubule were observed on the 15th day, but were less marked for the proximal tubule. This repair was slow and progressive. Persistent lesions of the proximal or distal tubules were still observed after two months. The glomeruli presented several alterations, which were always only moderate. Overall, paraquat induces serious life-threatening lesions of acute tubular necrosis in the absence of adequate intensive care.     

ATP potentiates interleukin-1 beta-induced MMP-9 expression in mesangial cells via recruitment of the ELAV protein HuR

Renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin (IL)-1 beta. We demonstrate here that the stable ATP analog adenosine 5'-O-(thiotriphosphate) (ATP gamma S) potently amplifies the cytokine-induced gelatinolytic content of mesangial cells mainly by an increase in the MMP-9 steady-state mRNA level. A Luciferase reporter gene containing 1.3 kb of the MMP-9 5'-promoter region showed weak responses to ATP gamma S but conferred a strong ATP-dependent increase in Luciferase activity when under the additional control of the 3'-untranslated region of MMP-9. By in vitro degradation assay and actinomycin D experiments we found that ATP gamma S potently delayed the decay of MMP-9 mRNA. Gel-shift and supershift assays demonstrated that three AU-rich elements (AREs) present in the 3'-untranslated region of MMP-9 are constitutively bound by complexes containing the mRNA stabilizing factor HuR. The RNA binding of these complexes was markedly increased by ATP gamma S. Mutation of each ARE element strongly impaired the RNA binding of the HuR containing complexes. Reporter gene assays revealed that mutation of one ARE did not affect the stimulatory effects by ATP gamma S, but mutation of all three ARE motifs caused a loss of ATP-dependent increase in luciferase activity without affecting IL-1 beta-inducibility. By confocal microscopy we demonstrate that ATP gamma S increased the nucleo cytoplasmic shuttling of HuR and caused an increase in the cytosolic HuR level as shown by cell fractionation experiments. Together, our results indicate that the amplification of MMP-9 expression by extracellular ATP is triggered through mechanisms that likely involve a HuR-dependent rise in MMP-9 mRNA stability.     

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.     

Worldwide experience with the Finetech-Brindley sacral anterior root stimulator

BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality.     

Results of a policy of primary repair of truncus arteriosus in the neonate

Although the early mortality for repair of truncus arteriosus has decreased in the modern era, routine correction in the neonate has not been widely adopted. To assess the results of our protocol of early repair, we reviewed 46 neonates and infants undergoing repair of truncus arteriosus at the University of Michigan Medical Center from January 1986 to January 1992. Their ages ranged from 1 day to 7 months (median 13 days) and weights from 1.8 kg to 5.4 kg (mean 3.1 kg). Repair was performed beyond the first month of life in only 8 patients, because of late referral in 7 and severe noncardiac problems in 1. Associated cardiac anomalies were frequently encountered, the most common being interrupted aortic arch (n = 5), nonconfluent pulmonary arteries (n = 4), hypoplastic pulmonary arteries (n = 4), and major coronary artery anomalies (n = 3). Truncal valve replacement was performed in 5 patients with severe regurgitation, 3 of whom also had truncal valve systolic pressure gradients of 30 mm Hg or more. The truncal valve was replaced with a mechanical prosthesis in 2 patients and with a cryopreserved homograft in 3 patients. Right ventricle-pulmonary artery continuity was established with a homograft in 41 patients (range 8 mm to 15 mm), a valved heterograft conduit in 4 (range 12 mm to 14 mm), and a nonvalved polytetrafluoroethylene tube in the remaining patient (8 mm). There were 5 hospital deaths (11%, 70% confidence limits 7% to 17%). Multivariate and univariate analyses failed to demonstrate a relationship between hospital mortality and age, weight, or associated cardiac anomalies. Only 1 death occurred among 9 patients with interrupted aortic arch or nonconfluent pulmonary arteries. Hospital survivors were followed-up from 3 months to 6.3 years (mean 3 +/- 0.4 years). Late noncardiac deaths occurred in 3 patients, all within 4 months after the operation. Actuarial survival was 81% +/- 6% at 90 days and beyond. Despite the prevalence of major associated conditions, early repair has resulted in excellent survival. We continue to recommend repair promptly after presentation, optimally within the first month of life.