Anti-RNA polymerase I antibodies in sera of MRL lpr/lpr and MRL +/+ autoimmune mice. Correlation of antibody production with delayed onset of lupus-like disease in MRL +/+ mice.

Sera from individual MRL/lpr and MRL/++ mice, which develop an autoimmune disease similar to human systemic lupus erythematosus (SLE), were screened over a period of approximately 30 wk for the presence of anti-RNA polymerase I and anti-ssDNA antibodies. Even though onset of the disease is delayed in MRL/++ as compared to MRL/lpr mice, anti-ssDNA antibodies were present in comparable concentrations in the sera of all mice by the age of 6 wk. As observed in sera of human SLE patients, anti-RNA polymerase I antibodies were detected in the sera of all MRL mice. However, unlike the anti-ssDNA antibodies, anti-RNA polymerase I antibodies were detected much later in MRL/++ mice (mean age, 22.8 wk) as compared to MRL/lpr mice (mean age, 9.6 wk). The presence of anti-RNA polymerase I antibodies in sera of MRL mice was thus a much better indicator of disease status than the presence of anti-ssDNA antibodies. The appearance and increase in anti-RNA polymerase I antibodies in the sera of MRL/++ mice correlated (R2 = 0.964) with a precipitous decrease in anti-ssDNA antibodies, starting at about 20 wk of age. These results suggest a possible relationship between the RNA polymerase I and DNA autoimmune reactions.

Effect of Severe Water Stress on Aspects of Crassulacean Acid Metabolism in Xerosicyos.

Xerosicyos danguyi H.Humb. (Cucurbitaceae) is a Crassulacean acid metabolism (CAM) species native to Madagascar. Previously, it was shown that when grown under good water conditions, it is a typical CAM plant, but when water stressed, it shifts to a dampened form of CAM, termed CAM-idling, in which stomata are closed day and night but with a continued, low diurnal organic acid fluctuation. We have now studied the kinetics of some metabolic features of the shift from CAM to CAM-idling under severe water stress and the recovery upon rewatering. When water is withheld, there is a steady decrease in relative water content (RWC), reaching about 50%, at which point the water potential decreases precipitously from about -2 or -3 bars to -12 bars. Abscisic acid (ABA) increases sharply at about 75% RWC. Stomata close, which limits CO2 uptake, and there is a dampened diurnal organic acid fluctuation typical of CAM-idling. Throughout an extended stress period to 50% RWC, there is no change in chlorophyll, protein, and ribulose bisphosphate carboxylase activity compared with the well-watered plants. Despite the fact that the tissue was already in CAM, the stress is accompanied by an increase in phosphoenolpyruvate carboxylase (PEPc) mRNA, extractable PEPc activity, and PEPc protein (such that the specific activity remained approximately constant) and a decrease in the apparent Km(PEP). It is not known if the changes in Km(PEP) in response to drought are related to or are separate from the increases in PEPc protein and mRNA. The changes in Km(PEP) could be in response to the decreased endogenous levels of organic acids, but evidently are not an assay artifact. The increases in PEPc protein and mRNA appear to be related to the water-stress treatment and may result from the increased concentration of ABA or the decreased levels of endogenous organic acids. When rewatered, the metabolism quickly returns to the well-watered control typical of CAM.

Gastroschisis and omphalocele: does either antenatal diagnosis or route of delivery make a difference in perinatal outcome?

The route of delivery for the fetus with an abdominal wall defect is controversial. This investigation proposed two null hypotheses: 1) The prognosis for the fetus with an abdominal wall defect is not affected by the timing of the diagnosis (antenatal or postnatal); and 2) the route of delivery does not affect fetal outcome. Sixty-one pregnancies complicated by either fetal gastroschisis (33) or omphalocele (28) delivered between December 1979 and January 1989 were reviewed. Seventy-one percent of the fetuses with gastroschisis and 59% with omphalocele were born vaginally. Gestational age at delivery, incidence of meconium staining, days to first neonatal oral feeding, percentage of neonates with one-stage closure of their defect, and percent of neonates with a birth weight less than the tenth percentile for gestational age were similar in fetuses with gastroschisis and with omphalocele, whether diagnosed antenatally or at birth. Significantly lower birth weights and longer neonatal hospitalizations were noted in the infants with omphalocele diagnosed antenatally compared with those diagnosed at birth (P less than .03), but no such differences were seen with gastroschisis. The route of delivery did not affect outcome for either defect. All fetuses born with gastroschisis and 87% with omphalocele free of associated lethal abnormalities were discharged alive. We conclude that the antenatal diagnosis of gastroschisis is not associated with either worse disease or a poorer outcome, though this may not be true for omphalocele. The good outcome with a high vaginal delivery rate suggests the need for a randomized trial of vaginal and cesarean delivery for fetal gastroschisis and omphalocele.

Evaluation of pressure transmission ratios in women with genuine stress incontinence and low urethral pressure: a comparative study.

OBJECTIVE: To determine whether women with genuine stress incontinence and low urethral closure pressure (20 cm H2O or lower) had more severely impaired pressure transmission to the urethra than women with stress incontinence and normal urethral pressures. METHODS: Seventy-six women who underwent multichannel urodynamic testing were included for comparative analysis. They were classified into the following groups: genuine stress incontinence with low urethral pressure (N = 20), genuine stress incontinence without low urethral pressure (N = 32), and continent controls (N = 24). Urodynamic indices and pressure transmission ratios were calculated from static and stress urethral pressure profiles, respectively. Multiple demographic cofactors, urethral mobility, and previous surgeries were correlated for associations with urodynamic results. RESULTS: Women with stress incontinence and low urethral pressure were significantly older (57.6 years, P < .0071). There were no differences with regard to urethral mobility and previous surgeries. Mean maximum urethral closure pressure and the distance from the proximal margin of the urethra to the point of maximum urethral closure pressure were statistically less in women with low urethral pressure. There were no differences in pressure transmission ratios between any of the study groups. CONCLUSION: Because there are no differences in pressure transmission ratios between women with genuine stress incontinence with and without low urethral closure pressure, the higher risk for surgical failure with low urethral pressure appears to result from another pathophysiologic process.

State, federal statutes guide organ donation procedures.

To assist in improving the network of organ donors and recipients and in raising public awareness, Congress enacted the National Organ Transplant Act of 1984. The act established an Organ Procurement and Transplantation Network, created a Task Force on Organ Transplantation, and made in unlawful to sell or buy human organs for transplantation for "valuable consideration." At the state level, legislation has closely followed the procedures outlined in the Uniform Anatomical Gift Act. But despite the state and federal statutes, a critical shortage of organs and tissues for transplantation persists. Addressing this problem, approximately 31 states have passed legislation that requires hospitals to request approval for donations from the relatives of potential donors. A generally positive public attitude toward organ transplantation suggests that eventually such legislation could help to increase the supply of organs. In the meantime, however, organ selection and prioritizing processes, particularly those which relate to geographic distribution, will continue to be closely scrutinized.

Kinetic Properties of Phosphoenolpyruvate Carboxylase in Peperomia camptotricha.

Kinetic characteristics of phosphoenolpyruvate carboxylase (PEPC) from the epiphytic C(3) or C(4): CAM intermediate plant, Peperomia camptotricha, were investigated. Few day versus night differences in V(max),K(m(PEP))), or malate inhibition were observed, even in extracts from water-stressed plants which characteristically perform CAM, regardless of efforts to stabilize day/night forms. The PEPC extracted from plants during the light period remained stable, without much of an increase or decrease in activity for at least 22 hours at 0 to 4 degrees C. Extracts from mature, fully developed leaves had slightly greater PEPC activity than from very young, developing leaves. Generally, however, the kinetic properties of PEPC extracted from mature leaves of plants grown under short day (SD), long day (LD), or 1-week water-stress conditions, as well as from young, developing leaves, were similar. The PEPC inhibitor, l-malate, decreased the V(max) and increased the K(m(PEP)) for all treatments. Under specific conditions, malate did not inhibit PEPC rates in the dark extracts as much as the light. The PEPC activator, glucose-6-phosphate (G-6-P), lowered the K(m(PEP)) for all treatments. At saturating PEP concentrations, PEPC activity was independent of pH in the range of 7.5 to 9.0. At subsaturating PEP concentrations, the pH optimum was 7.8. The rates of PEPC activity were lower in the light period extracts than the dark, at pH 7.1, but day/night PEPC was equally active at pH 7.8. At pH 7.5 and a subsaturating PEP concentration, G-6-P significantly activated PEPC. At pH 8, however, only slight activation by G-6-P was observed. The lower pH of 7.5 combined with l-malate addition, greatly inhibited PEPC, particularly in extracts from young, developing leaves which were completely inhibited at an l-malate concentration of 1 millimolar. However, malate did not further inhibit PEPC activity in mature leaves when assayed at pH 7.1. The fairly constant day/night kinetic and regulatory properties of PEPC from P. camptotricha are unlike those of PEPC from CAM or C(4) species studied, and are consistent with the photosynthetic metabolism of this plant.

Crassulacean Acid Metabolism and Crassulacean Acid Metabolism Modifications in Peperomia camptotricha.

Peperomia camptotricha, a tropical epiphyte from Mexico, shows variable forms of Crassulacean acid metabolism (CAM). Young leaves exhibit CAM-cycling, while mature leaves show an intermediate type of metabolism, between CAM and CAM-cycling, having approximately the same amount of nighttime gas exchange as daytime. Metabolism of young leaves appears independent of daylength, but mature leaves have a tendency toward more CAM-like metabolism under short days (8 hours). Large differences in the physical appearance of plants were found between those grown under short daylengths and those grown under long daylengths (14 hours). Some anatomical differences were also detected in the leaves. Water stress caused a switch to CAM in young and mature leaves, and as water stress increased, they shifted to CAM-idling.

Enhancement of B-cell translocation gene-1 expression by prostaglandin E2 in macrophages and the relationship to proliferation.

Although prostaglandin (PG) E2 is known to suppress various macrophage functions, the molecular mechanisms by which that occurs are largely unknown. To understand better those mechanisms, differential screening of a cDNA library from PGE2-treated macrophages was performed. Subsequently, the DNA sequence of a differentially expressed cDNA clone was determined and the cDNA was identified as B-cell translocation gene-1 (BTG1), a recently cloned antiproliferative gene. A two-to threefold increase in macrophage BTG1 expression was observed after PGE2 treatment. PGE1 and platelet-activating factor, but not leukotrienes B4, and C4, or lipopolysaccharide, also enhanced BTG1 expression. Furthermore, this effect ws mimicked by dibutyryl cAMP which indicated the involvement of elevated cAMP in the PGE2-mediated enhancement of BTG1. Moreover, there was an inverse correlation between BTG1 mRNA expression and macrophage proliferation; however, BTG1 alteration was not associated with macrophage tumoricidal activation. Thus, BTG1 may play a role in PGE2-mediated inhibition of macrophage proliferation and not activation.

Citrus Tissue Culture : AUXINS IN RELATION TO ABSCISSION IN EXCISED PISTILS.

An in vitro bioassay for chemicals that affect Citrus abscission was used to identify three inhibitors of stylar abscission in lemon pistil explants incubated on defined nutrient media. The three inhibitors (picloram, 4-chlorophenoxyacetic acid, and 3,5,6-trichloropyridine-2-oxyacetic acid) are all auxins, and the most potent of them (i.e. picloram) was found to be at least 10 times more active in the bioassay than 2,4-dichlorophenoxyacetic acid. Picloram (2 micromolar) also was shown to be effective in inhibiting stylar abscission in pistil explants from other Citrus cultivars such as mandarin, Valencia, and Washington navel oranges and grapefruit. To study the physiology of auxins active as abscission inhibitors versus inactive auxins in lemon pistils, the transport and metabolism of [1-(14)C]-2,4-dichlorophenoxyacetic acid was compared with that of [2-(14)C]indole-3-acetic acid, which is without effect in the bioassay over the range from 0.1-100 micromolar. Insignificant quantities of labeled indole-3-acetic acid and/or labeled derivatives were found to reach the presumptive zone of stylar abscission under the test conditions. Labeled 2,4-dichlorophenoxyacetic acid and/or labeled derivatives also were transported slowly through pistils, but some radioactivity could be detected in the stylar abscission zone as early as 24 hours after the start of incubation. Extensive conversion of [2-(14)C]indole-3-acetic acid to labeled compounds tentatively considered to be glycoside and cellulosic glucan derivatives was found with the use of solvent extraction methodology. A significantly smaller percentage of the radioactivity in pistils incubated on [1-(14)C]-2,4-dichlorophenoxyacetic acid was found in fractions corresponding to these derivatives. Both transport and metabolism appear to be important factors affecting the activity of auxins as abscission inhibitors in the bioassay.