Prevalence of infective endocarditis in patients with systemic lupus erythematosus.

BACKGROUND: Compared with the general population, patients with systemic lupus erythematosus, or SLE, have an increased prevalence of functionally impaired cardiac valves due to the presence of Libman-Sacks lesions. These lesions may place patients with SLE at risk of developing infective endocarditis, or IE. METHODS: The authors performed a retrospective chart review to determine the association between SLE with valvulopathy and IE. They reviewed the records of 361 patients from two health care facilities who had the diagnostic code of SLE. RESULTS: Of the 275 records that met the 1982 revised American Rheumatism Association criteria for SLE, 51 (18.5 percent) were for patients who had a clinically detectable heart murmur that resulted in echocardiography being performed. Nine (3.3 percent) of the 275 patients had a clinically significant valvular abnormality, three (1.1 percent) had a potentially significant valvular abnormality, and one (0.4 percent) had a history of IE that was diagnosed two years before her diagnosis of SLE was made. CONCLUSIONS: The findings suggest that 18.5 percent of this cohort of patients with SLE had a clinically detectable heart murmur that would require further investigation to determine its significance. Furthermore, between 3.3 and 4.4 percent of the study population had cardiac valve abnormalities that potentially required antibiotic prophylaxis before certain dental procedures. However, the authors identified no cases that demonstrated an association between IE and diagnosed SLE. CLINICAL IMPLICATIONS: Dentists should query their patients with SLE about their cardiac status and consult with the patient's physician if the cardiac status is unknown. Patients with confirmed valvular abnormalities should receive antibiotic prophylaxis for designated bacteremia-producing dental procedures.

An RNA 5'-triphosphatase related to the protein tyrosine phosphatases.

mRNA capping requires the sequential action of three enzymatic activities: RNA triphosphatase, guanylyl-transferase, and methyltransferase. Here we characterize a gene (CEL-1) believed to encode the C. elegans capping enzyme. CEL-1 has a C-terminal domain containing motifs found in yeast and vaccinia virus capping enzyme guanylyltransferases. The N-terminal domain of CEL-1 has RNA triphosphatase activity. Surprisingly, this domain does not resemble the vaccinia virus capping enzyme but does have significant sequence similarity to the protein tyrosine phosphatase (PTP) enzyme family. However, CEL-1 has no detectable PTP activity. The mechanism of the RNA triphosphatase is similar to that of PTPs: the active site contains a conserved nucleophilic cysteine required for activity. These results broaden the superfamily of PTP-like phosphatases to include enzymes with RNA substrates.

Confirmation or exclusion of stage I hypertension by ambulatory blood pressure monitoring.

Criteria for the diagnosis or exclusion of hypertension using ambulatory blood pressure monitoring have not been agreed upon. We designed this study to provide a statistically based guide for using results of ambulatory blood pressure monitoring to resolve this issue. To generate this information, we used a database of 228 subjects (135 men, 93 women; average age, 45 years) referred by their primary physicians over the past 7 years for evaluation of borderline or stage I hypertension (average blood pressure, 148/92 mm Hg; SD, +/-17.5/12.2 mm Hg). In this population, the pooled SDs of systolic and diastolic ambulatory blood pressures were 13.8 and 11.6 mm Hg, respectively. Using the pooled SD, we calculated the probability that a patient's blood pressure falls within the hypertensive range (> 140/90 mm Hg). The 95% confidence interval for each subject's blood pressure was also determined. For example, if 40 ambulatory blood pressure measurements are performed on a subject and the average systolic ambulatory blood pressure is 137 mm Hg, then there is a 10% probability that the patient's "true" average blood pressure is actually in the hypertensive range. By contrast, if the systolic pressure is 143 mm Hg, there is a 90% probability that the patient is hypertensive. This approach may be useful for clinical decision making and also for the design of clinical trials.

mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain.

Capping of mRNA occurs shortly after transcription initiation, preceding other mRNA processing events such as mRNA splicing and polyadenylation. To determine the mechanism of coupling between transcription and capping, we tested for a physical interaction between capping enzyme and the transcription machinery. Capping enzyme is not stably associated with basal transcription factors or the RNA polymerase II (Pol II) holoenzyme. However, capping enzyme can directly and specifically interact with the phosphorylated form of the RNA polymerase carboxy-terminal domain (CTD). This association occurs in the context of the transcription initiation complex and is blocked by the CTD-kinase inhibitor H8. Furthermore, conditional truncation mutants of the Pol II CTD are lethal when combined with a capping enzyme mutant. Our results provide in vitro and in vivo evidence that capping enzyme is recruited to the transcription complex via phosphorylation of the RNA polymerase CTD.

Proteolytic fragments of the nicotinic acetylcholine receptor identified by mass spectrometry: implications for receptor topography.

A triple-state quadrupole or a tandem quadrupole Fourier-transform mass spectrometer was used to detect and sequence the peptides released by proteolytic cleavage of the acetylcholine receptor (AcChR) from Torpedo californica electroplax. Fragments in mass range up to 3479 daltons were characterized on the above instrumentation and used to determine proteolytically accessible sites on the receptor. These data were consistent with the cleavage points determined for membrane-bound fragments of the same AcChR samples using gas-phase microsequencing. Each subunit of the receptor is readily cleaved near the C-terminus in the region between the proposed transmembrane hydrophobic alpha-helices MIII and MIV. This region includes the putative regulatory phosphorylation sites and the amphipathic alpha-helix. Cleavage is also observed in the N-terminal domain, but occurs much more slowly than in the C-terminal region. No cleavage was detected in the middle third of the receptor, which includes the proposed transmembrane alpha-helices MI and MII. An evaluation of these data in terms of the transmembrane topography of the AcChR peptides is consistent with a synaptic or extracellular disposition for the region between MIII and MIV.

Rheologic behavior of deoxyhemoglobin S gels.

The physical properties of deoxyhemoglobin S gels formed from solutions at concentrations and temperatures approaching those in vivo have been characterized by stress relaxation using a rotational rheometer. Gels were annealed in the rheometer and then subjected to a constant shear strain; thereafter the stress sustained was followed with time. Gels with solid-like behavior held stress indefinitely, and were characterized by yield temperature (the temperature at which stress decreased). Gels with less solid behavior were unable to hold target stress, and were characterized by yield stress (maximum stress attained) and equilibrium stress (final stress held). The samples were ultracentrifuged to calculate pellet and polymer masses. The solidity of the gels, as measured by yield temperature or yield stress, was related to the initial hemoglobin concentration, pellet and polymer masses, shear history, temperature, and the temperature and time of annealing. Solidity increased significantly with time when gels were annealed at 37 degrees C, whereas, when annealed at 25 degrees C, no or minimal increases in solidity were noted. Studies suggest that polymerization occurs rapidly and is completed early in or before the gel annealing period and that the increase in solidity with time of annealing is mainly due to factors other than polymer mass, i.e. alignment, increasing bond strength, water loss. The chemical activity of deoxyhemoglobin S did not affect the solidity of the formed gels. When the resultant polymer masses were comparable, gels formed from samples with albumin present (higher initial total protein concentration, but lower initial deoxyhemoglobin S concentration), had the same behavior as gels formed from solutions with higher initial hemoglobin S concentration. These findings demonstrate that gel annealing conditions must be standardized when comparing the rheologic behaviors of deoxyhemoglobin S gels and indicate that the gel's physical properties (influenced by polymer mass, shear history, annealing time) must be considered in understanding pathophysiology of sickling disorders.

Time-dependent binding of paramagnetic and fluorescent hydrophobic ions to the acetylcholine receptor from Torpedo.

In receptor-rich vesicles isolated from Torpedo, paramagnetic or fluorescent phosphonium ions bind to both the acetylcholine receptor (AcChR) and the receptor membrane. When added to receptor vesicles, two to three phosphoniums undergo a slow time-dependent binding to the AcChR. The presence of agonist increases the rate but not the extent of binding of the alkylphosphonium nitroxides. Approximately one phosphonium per receptor can be displaced by the addition of saturating concentrations of the high-affinity histrionicotoxin derivative isodihydrohistrionicotoxin or by the addition of phencyclidine or quinacrine mustard. In addition, preincubation of the receptor with these channel blockers prevents approximately one phosphonium from binding to the receptor. When a series of alkyltriphenylphosphonium ions was studied, it was found that the rate of phosphonium binding to the receptor decreased with increasing probe hydrophobicity. This appears to be a function of the partitioning of the probe between membrane and aqueous phases. The phosphonium ions used here promote desensitization of the receptor, as judged by the binding rate of the fluorescent agonist NBDA-C5-acylcholine or alpha-bungarotoxin. Preincubation of the receptor with isodihydrohistrionicotoxin virtually eliminates the phosphonium-mediated desensitization. The rates of the phosphonium-mediated desensitization also appear to be dependent upon the phase partitioning of the probe. These results strongly suggest that the binding sites for the phosphonium ion (and the high-affinity histrionicotoxin blocking site) are accessible only through the aqueous phase. The phosphonium binding and agonist-induced transitions observed here are not observed with a negative hydrophobic ion probe, or a negative surface amphiphile, indicating that modifications in membrane electrostatics do not contribute to the observed changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicities with intravenous and subcutaneous administration of a petroleum distillate.

Although ingestion of petroleum distillates is common, injection of these products has not been widely reported. The effects of subcutaneous administration have not been fully documented. Presented is a 27-year-old male who developed a sterile abscess and pneumonitis following concurrent intravenous and subcutaneous administration of a petroleum distillate.

Protein, glycoprotein and glycolipid profiles of human arterial and venous tissues.

Selected normal human arteries and veins were solubilized with detergents, neutral salt buffers and organic solvents. Comparative sodium dodecyl sulphate polyacrylamide gels and thin layer chromatographic plates were developed and the patterns compared. The low molecular weight periodic acid--Schiff positive band seen in crude detergent extracts of vascular tissue is predominantly glycolipid. Arterial and venous tissues closely resemble one another with only minor differences in the glycoprotein and glycolipid patterns.