Systemic lupus erythematosus: perinatal and neonatal implications

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost all organ systems in the body. It is most common in women of childbearing age and may cause multiple peripartum complications. This article reviews the pathophysiology of SLE and the effects of SLE on fertility and pregnancy. The complexities of managing a pregnant patient with SLE are reviewed, and the importance of interdisciplinary collaboration discussed, as well as the effects of SLE on the fetus and a review of neonatal lupus erythematosus. Finally, a case report of a pregnant patient with SLE with challenging clinical management issues is presented.     

Inhibition of DNA cytosine methyltransferase by chemopreventive selenium compounds, determined by an improved assay for DNA cytosine methyltransferase and DNA cytosine methylation

The organoselenium compounds benzyl selenocyanate (BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC), as well as sodium selenite, are effective chemopreventive agents for various chemically induced tumors in animal models at both the initiation and postinitiation stages. The mechanisms involved at the postinitiation stage are not clear. Because several lines of evidence indicate that inhibition of excess DNA (cytosine-5)-methyltransferase (Mtase) may be a sufficient factor for the suppression or reversion of carcinogenesis, we examined the effects of sodium selenite, BSC, p-XSC and benzyl thiocyanate (BTC), the sulfur analog of BSC, on Mtase activity in nuclear extracts of human colon carcinomas, and of p-XSC on the Mtase activity of HCT116 human colon carcinoma cells in culture. For this purpose, we developed an improved Mtase assay, in which the incorporation of the methyl-[3H] group from S-adenosyl[methyl-3H]methionine into deoxycytidine of poly(dI-dC)-poly(dI-dC), is specifically determined by HPLC with radioflow detection after enzymatic hydrolysis, enhancing specificity and reliability. In a variation, using SssI methyltransferase and labeled S-adenosylmethionine, the overall methylation status of DNA in various tissues can also be compared. Selenite, BSC and p-XSC inhibited Mtase extracted from a human colon carcinoma with IC50s of 3.8, 8.1 and 5.2 microM, respectively; BTC had no effect. p-XSC also inhibited the Mtase activity and growth of human colon carcinoma HCT116 cells, with an IC50 of approximately 20 microM. The improved Mtase assay should prove to be a reliable method for screening potential Mtase inhibitors, especially using cells in culture. We suggest that inhibition of Mtase may be a major mechanism of chemoprevention by selenium compounds at the postinitiation stage of carcinogenesis.     

Selective effects of different antioxidants on oxidation of lipoproteins from rats

Constipation in childhood is often unrecognized and diagnosed upon manifestations such as pain and pseudo-diarrhoea reflecting of a fecalith. It is sometimes complicated with urinary infection and can be a factor favouring enuresis. In the absence of deterioration in the general condition, it reflects modification of the propulsive functions of the colon or of the reservoir function of the rectum. In a such context, no further explorations are required. Treatment involves dietary recommendations such as good nutritional balance and sufficient fibre intake as well as mineral-based laxatives (paraffin oil) or nonabsorbable osmotic sugars. Enemas and suppositories should be used in case of stool withholding. Sphincter reeducation by biofeedback is indicated in child over 8 years of age after failure of medical therapy.     

Evaluation of the detectability of breast cancer lesions using a modified anthropomorphic phantom

During the development and characterization of imaging technology or new imaging protocols, it is usually instructive to perform phantom experiments. Often, very simplified forms of the realistic patient anatomy are used that may be acceptable under certain conditions; however, the implications for patient studies can be misleading. This is particularly true in breast and axillary node imaging. The complexities presented by the anatomy, variable object scatter, attenuation and inhomogeneous distribution of activity in this upper thoracic region provide a significant challenge to the imaging task. METHODS: A tissue-equivalent anthropomorphic phantom of the thorax (Radiology Support Devices, Inc., Long Beach, CA) containing fillable cavities and organs was modified for the studies. The phantom was filled with realistic levels of FDG activity and scanned on a Siemens ECAT HR+ whole-body PET scanner. Breast attachments containing 2.0- and 2.55-cc lesions with lesion-to-background ratios of 5:1 and 7:1, respectively, were imaged. Scatter and attenuation effects were analyzed with various experimental setups. A lymph node experiment and a multibed position whole-phantom scan also were performed to illustrate the extent to which the phantom represents the human thorax. RESULTS: Regions of interest were drawn on the lesions as well as the background breast tissue in all studies. It was found that the signal-to-noise ratio decreased 65% when a more realistic phantom (lesions plus breasts plus thorax, all containing activity) was used, as compared to a simple phantom (lesions plus breasts containing activity; no thorax), due to the effects of increased scatter and attenuation. A 23% decrease in the contrast also was seen from the scan of the more realistic phantom due to surrounding activity from nearby organs such as the heart, as well as an increase in the volume of attenuating media. CONCLUSION: This new phantom allows us to more realistically model the conditions for breast and lymph node imaging, leading to preclinical testing that will produce results that better approximate those that will be found in vivo. The phantom will be a valuable tool in comparing different imaging technologies, data collection strategies and image reconstruction algorithms for applications in breast cancer using PET, SPECT or scintimammography systems.     

Characterization of the testis and epididymis in mouse models of human Tay Sachs and Sandhoff diseases and partial determination of accumulated gangliosides

Beta-hexosaminidase (Hex) is an essential lysosomal enzyme whose activity is higher in the epididymis than in other tissues. The enzyme is also present in sperm and has been postulated to be required for fertilization. To better understand the role of Hex in reproduction, we have examined the testes and epididymides of mouse models of human Tay Sachs and Sandhoff diseases, produced by targeted disruption of the Hexa (alpha-subunit) or Hexb (beta-subunit) genes, respectively, encoding the enzymes Hex A (structure, alphabeta) and Hex B (betabeta). Testis weight, morphology, and sperm counts were unaffected in Hex-deficient mice. In the epididymis of the Hex A-deficient Hexa-/- mice, there was a large increase in the size and number of lysosomes in the initial segment/intermediate zone. In Hexb-/- mice (Hex A and B-deficient), the epididymal defects were much more extensive and the cytoplasm of all cell types throughout the efferent ducts and epididymis was filled with pale, uncondensed, enlarged lysosomes. In contrast to the brain where GM2 ganglioside accumulates, both mutant mice accumulated two non-GM2 gangliosides in the epididymis. The major accumulated species was characterized by electrospray ionization tandem mass spectrometry. The Hexa-/- male mice were fertile; however, litter sizes were reduced. The Hexb-/- males were able to sire normal sized litters up to nine weeks of age and remained healthy until 16-20 weeks of age. The extensive abnormalities in the Hexb-/- mice, in contrast to region-specific effects in the Hexa-/-mice, indicate an important and novel role for the Hex B isozyme in the epididymis and a region-specific role for Hex A in the initial segment/intermediate zone. In contrast to other reports, our results indicate that Hex is not essential for fertilization in young adult male mice. To explain the extensive epididymal abnormalities in the Hexb-/- mice, we propose that substrates for Hex, such as testis-derived glycolipids, cannot be catabolized and accumulate in lysosomes, leading to epididymal dysfunction and abnormalities in the epididymal luminal environment that supports sperm maturation.     

Spatial and physical frames of reference in positioning a limb

Splints attached to the right forearm were used to rotate the forearm's physical reference frame, as defined by the eigenvectors of its inertia tensor, relative to its spatial reference frame. In two experiments, when subjects were required to orient the forearm parallel to, or at 45 degrees to, the environmental horizontal, they produced limb orientations that were systematically deflected from the forearm's longitudinal spatial axis in the direction of the forearm's physical axes. The position sense seems to be based on inertial eigenvectors rather than on joint angles or gravitational torques.     

Modulation of GDP-dissociation inhibitor protein membrane retention by the cellular redox state in adipocytes

Genetic screens in zebrafish have provided mutations in hundreds of genes with essential functions in the developing embryo. To investigate the possible uses of chromosomal rearrangements in the analysis of these mutations, we genetically characterized three gamma-ray induced alleles of cyclops (cyc), a gene required for development of midline structures. We show that cyc maps near one end of Linkage Group 12 (LG 12) and that this region is involved in a reciprocal translocation with LG 2 in one gamma-ray induced mutation, cyc(b213). The translocated segments together cover approximately 5% of the genetic map, and we show that this rearrangement is useful for mapping cloned genes that reside in the affected chromosomal regions. The other two alleles, cyc(b16) and cyc(b229), have deletions in the distal region of LG 12. Interestingly, both of these mutations suppress recombination between genetic markers in LG 12, including markers at a distance from the deletion. This observation raises the possibility that these deletions affect a site required for meiotic recombination on the LG 12 chromosome. The cyc(b16) and cyc(b229) mutations may be useful for balancing other lethal mutations located in the distal region of LG 12. These results show that chromosomal rearrangements can provide useful resources for mapping and genetic analyses in zebrafish.     

Application of cloud-point extraction-reversed-phase high-performance liquid chromatography. A preliminary study of the extraction and quantification of vitamins A and E in human serum and whole blood

Acute intestinal graft-versus-host disease (GVHD) develops in about 30-50% of allogeneic bone-marrow transplant recipients: 10-20% have gastrointestinal emergencies (hemorrhage or perforation). Mortality reaches 30-60% in patients with acute, grade 2-4 GVHD. We studied 36 bone marrow recipients in whom acute intestinal GVHD developed. Seven had gastrointestinal emergencies: 4 severe gastrointestinal bleeding and 3 acute peritonitis. Three patients with gastrointestinal bleeding and one patient with peritonitis responded to medical therapy. Three needed surgery: one with bleeding and two with peritonitis, while 1 patient had embolization. Of the 7, two patients died, one after embolization and one after surgery. Two of the three surgically-treated cases are still alive several years after operation. From this experience we feel that surgery for gastrointestinal bleeding in acute GVHD is indicated only when medical treatment fails. Severe neutropenia, thrombocytopenia (<10.000 x mm3) and blood cultures positive for CMV have an unfavorable prognostic value.