Extracellular processing of peptide antigens that bind class I major histocompatibility molecules.

One problem associated with the use of synthetic peptides as antigens in vivo is their susceptibility to inactivation by proteolytic degradation. A situation is described in which a serum protease, angiotensin-converting enzyme (ACE), is actually responsible for the class I binding activity of a commonly used influenza antigen, nucleoprotein (NP)(147-158R-). This peptide has been reported to be a highly efficient class I antigen. Evidence is presented that demonstrates that the peptide is inactive until cleaved by ACE, which is a normal constituent of serum. The enzyme removes a COOH-terminal dipeptide resulting in the sequence NP(147-155), which is identical to the naturally processed peptide. Such extracellular processing of peptides and proteins may occur for a variety of antigens both in vitro and in vivo, and could have important implications for the design of proteolytically resistant vaccines.     

Natural history of liver imaging reporting and data system category 4 nodules in MRI

Purpose: The purpose of this study was to characterize the MR imaging features and outcomes of liver imaging reporting and data system (LI-RADS) category 4 (LR4) nodules, with an emphasis on upgrade to category 5 (LR5) and development of contraindications to curative therapy. Methods: Institutional review board approval was obtained for this retrospective, dual-institutional Health Insurance Portability and Accountability Act-compliant study. The requirement for informed consent was waived. Contrast-enhanced MRI studies performed on patients with cirrhosis were retrospectively assessed using LI-RADS 2014 by at least two readers. All nodules were individually evaluated to determine their major imaging features at diagnosis, and follow-up data were used to determine the associated imaging outcomes. Results: One hundred eighty-one untreated LR4 nodules in 139 patients had adequate imaging and follow-up for inclusion in the study. Most (61% [111/181]) of these demonstrated arterial phase hyperenhancement, washout, and diameter less than 20 mm. During the follow-up period (median 163 days), 31% (56/181) of the nodules upgraded to LR5, 40% (73/181) remained stable, and 29% (52/181) downgraded. Of the nodules that upgraded, 61% (34/56) increased their size category and 54% (30/56) developed newly visualized capsules. No LR4 nodules developed venous invasion, satellites nodules, or new intrahepatic or extrahepatic metastatic disease. 75% (42/56) of the nodules that upgraded to LR5 did so within 6 months. Conclusions: Approximately one-third of LR4 nodules upgrade to LR5, and the short-term risk of developing venous invasion or metastasis is very low.     

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature. Administration of the NOS inhibitor l-NAME to pregnant mice recapitulated the angiotensin sensitivity and oxidative stress observed with sFlt1 overexpression. Sildenafil, an FDA-approved phosphodiesterase 5 inhibitor that enhances NO signaling, reversed sFlt1-induced hypertension and angiotensin II sensitivity in the preeclampsia mouse model. Sildenafil treatment also improved uterine blood flow, decreased uterine vascular resistance, and improved fetal weights in comparison with untreated sFlt1-expressing mice. Finally, sFLT1 protein expression inversely correlated with reductions in eNOS phosphorylation in placental tissue of human preeclampsia patients. These data support the concept that endothelial dysfunction due to high circulating sFLT1 may be the primary event leading to enhanced vasoconstrictor sensitivity that is characteristic of preeclampsia and suggest that targeting sFLT1-induced pathways may be an avenue for treating preeclampsia and improving fetal outcomes.     

Pathology of the thin-cap fibroatheroma: a type of vulnerable plaque

Thin cap atheroma is the precursor of plaque rupture, which accounts for a majority of coronary thrombi. The morphologic features of thin cap atheromas that predict rupture are unknown, but we know from studies of ruptured plaques that large necrotic cores, fibrous cap < 65 microns and numerous macrophages within the cap likely indicate instability. There is some evidence that a speckled pattern of calcification is associated with vulnerability to rupture. There are usually multiple thin cap atheroma in the hearts of patients dying with acute plaque rupture, as well as multiple fibroatheromas with intraplaque hemorrhage. Targeted therapy for the purpose of stabilizing coronary lesions that are prone to rupture is a major future goal of the interventionist.     

A randomized,double-blind trial of the effect of metronidazole on pain after closed hemorrhoidectomy

PURPOSE: Patients consider hemorrhoidectomy to be a painful operation. Attempts to reduce the length of inpatient stay have concentrated mainly on a reduction in postoperative pain. Metronidazole has been shown to reduce pain after open hemorrhoidectomy. The aim of this study was to evaluate the effect of metronidazole after closed hemorrhoidectomy. METHODS: Thirty-eight patients undergoing closed hemorrhoidectomy were randomly allocated to receive metronidazole 400 mg (n = 18) or placebo (n = 20) three times daily for seven postoperative days. All patients received a stool softener and analgesics perioperatively. Linear analog scales were used to assess expected pain, actual pain and patient satisfaction. Time to first bowel movement, return to normal activity, complications, and use of additional analgesics were recorded. RESULTS: Both groups of patients experienced less pain than expected. Patients in the metronidazole group required fewer additional analgesics postoperatively (6.3 vs. 26.3 percent), and satisfaction scores in the placebo group were higher at one week (0.5 vs. 2.5), although these differences were not statistically significant. There were no differences in pain actually experienced, time to first bowel movement, return to normal activity, or complications between the two groups. Satisfaction scores at six weeks for all patients were relatively high, with no significant difference between the groups. CONCLUSION: Closed hemorrhoidectomy results in high patient satisfaction and low pain scores. The use of postoperative metronidazole did not reduce postoperative pain.     

急性非淋巴细胞白血病分型与红细胞AB抗原表达强度相关性研究4例报告及文献复习

目的:分析研究急性非淋巴细胞白血病(ANLL)分型与红细胞AB抗原表达强度相关性。方法:临床诊断ANLL患者红细胞AB抗原表达强度减弱4例,并复习国内近26年文献中完整资料77例病例报告一起进行分析。结果:81例ANLL中红细胞A抗原、B抗原、AB抗原同时表达减弱分别为51.85%、39.51%、8.64%。在ANLL中M2型最为多见,其次依次为M1型、M5型、M3型。结论:在进行ANLL患者红细胞ABO血型鉴定时,必须应用高效价抗血清试剂(≥128)进行正定型鉴定,以防止由于患者红细胞AB血型抗原表达减弱所致血型误判。