Renal allografts in acute rejection: evaluation using duplex sonography

Sixty-nine duplex sonographic studies were performed in 24 patients who had received renal allografts. After a prospective qualitative analysis of the Doppler waveforms, results were correlated with biopsy material and each patient's clinical course. Increased pulsatility of the Doppler waveform of intrarenal arterial flow constituted an abnormal study, indicating acute rejection. Overall sensitivity varied with the histologic form of rejection, with a 60% sensitivity for acute interstitial rejection with or without vascular rejection and an 82% sensitivity for acute vascular rejection. Overall specificity was 95% and 96%, respectively. Early rejection was also accurately detected in three patients less than 48 hours following kidney transplantation. Duplex sonography has a useful role in evaluating posttransplantation renal failure. Abnormal study results may obviate the need for biopsy and help in guiding clinical management.     

Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells

Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.     

Increased basal and induced tyrosine phosphorylation of the insulin- like growth factor I receptor beta subunit in circulating mononuclear cells of patients with polycythemia vera

We have previously shown that circulating progenitor cells in patients with polycythemia vera (PV) are hypersensitive to insulin-like growth factor I (IGF-I) with respect to erythroid burst formation in serum- free medium, and that this effect occurs through the IGF-I receptor. To investigate the molecular basis of this IGF-I hypersensitivity phenomenon, we examined tyrosine phosphorylation of the IGF-I receptor beta subunit in peripheral blood mononuclear cells (PBMNC) from eight PV patients and six normals. Cells were exposed to IGF-I at concentrations of 10(-8) and 10(-10) mol/L for 0, 1, 3, and 10 minutes, and then lysed. The IGF-I receptor beta subunit was immunoprecipitated, and the protein was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotted with antiphosphotyrosine antibody (4G10). We found that, in the absence of exogenous IGF-I, there was a basal level of tyrosine phosphorylation of the IGF-I receptor beta subunit, and it was substantially greater in PV than in normal. At 10(-10) mol/L IGF-I in normals, no evidence of increased tyrosine phosphorylation was detected; however in PV, a pronounced increase in tyrosine phosphorylation was observed at both 10(-10) and 10(-8) mol/L IGF-I, and it occurred earlier and attained a higher level than in normal. In contrast, in PBMNC from three patients with erythrocytosis, no significant increase above normal was seen in either basal or induced tyrosine phosphorylation of the IGF-I receptor beta subunit. Thus, our findings show two distinctive features of the PV phenotype in PBMNC: (1) an increased basal tyrosine phosphorylation of the IGF-I receptor beta subunit, and (2) a hypersensitive and hyperresponsive receptor with respect to tyrosine phosphorylation. These features may influence the ability of the receptor to transmit a proliferative signal; thus, they may play a role in the pathogenesis of PV.     

Gastrinomas: comparison of MR imaging with CT, angiography, and US

In this prospective study, magnetic resonance (MR) imaging was used to localize gastrinoma in 24 patients with Zollinger-Ellison syndrome. The results were confirmed by means of either surgery or percutaneous liver biopsy and compared with results of computed tomographic (CT) scanning, selective abdominal angiography, and abdominal ultrasound (US). For primary extrahepatic gastrinoma (intra-or extrapancreatic), MR imaging had a sensitivity of 20% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 11%. For metastatic gastrinoma in the liver, MR imaging had a sensitivity of 43% and a specificity of 100%, with a positive predictive value of 100% and a negative predictive value of 81%. The ability of MR imaging to depict extrahepatic gastrinomas was directly related to tumor size; no tumors smaller than 1 cm were detected, and 50% of tumors 3 cm or larger were detected. MR imaging was as effective as abdominal US but less effective than either CT scanning or selective abdominal angiography for the detection of extrahepatic gastrinoma. In seven patients with hepatic gastrinoma, three gastrinomas were detected with MR imaging and with abdominal US, while five were detected with CT scanning and with selective abdominal angiography. These results indicate that, at the present time, MR imaging is generally not useful in the initial attempt to localize gastrinomas.     

Rheumatoid arthritis: MR imaging manifestations

Radiologic assessment of the stage and treatment response of rheumatoid arthritis (RA) is based on the presence of bone erosions, joint-space narrowing, and osteoporosis. Most radiologic methods for staging RA lack interobserver correlation and are time consuming. Magnetic resonance (MR) imaging provides excellent depiction of soft-tissue abnormalities of the joints affected by RA, which allows detection of early changes. Nineteen joints of 17 patients with RA were studied with surface-coil MR imaging. Measurable abnormalities demonstrated by MR imaging but not clearly seen on plain radiographs included bone erosions, joint effusion, synovial sheath effusion, and cartilage irregularity and thinning. Seven patients of this group underwent MR imaging before and after 6 months of gold therapy. Four patients had significant interval changes on MR images that were not seen on plain radiographs. MR imaging may become a sensitive and objective method for quantitative assessment of the joint changes of RA.