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Biomedical subjects

B J Wagner

Publications and source records attributed to B J Wagner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Structural determinants in AUF1 required for high affinity binding to A + U-rich elements.

AUF1 is an RNA-binding protein that contains two nonidentical RNA recognition motifs (RRMs). AUF1 binds to A + U-rich elements (AREs) with high affinity. The binding of AUF1 to AREs is believed to serve as a signal to an mRNA-processing pathway that degrades mRNAs encoding many cytokines, oncoproteins, and G protein-coupled receptors. Because the ARE binding activity of AUF1 appears central to the regulation of many important genes, we analyzed the domains of the protein that are important for this activity. Examination of the RNA binding affinity of various AUF1 mutants suggests that both RRMs may be required for binding to the human c-fos ARE. However, the two RRMs together are not sufficient. Highest affinity binding of AUF1 to an ARE requires an alanine-rich region of the N terminus and a short glutamine-rich region in the C terminus. In addition, the N terminus is required for dimerization of AUF1. However, AUF1 binds an ARE as a hexameric protein. Thus, protein-protein interactions are important for high affinity ARE binding activity of AUF1.

Adenine↗
PubMed1997

Radiologic assessment of renal masses: implications for patient care.

The relationships between the gross pathologic features of neoplastic and nonneoplastic renal masses and their radiologic analogues, described above, establish specific guidelines for the influence of radiologic studies on clinical management. A tumor that contains fat, as determined with CT or MR imaging, can be confidently diagnosed as an angiomyolipoma without further diagnostic intervention. The size of the lesion should be used to influence clinical decisions related to the fact that angiomyolipomas larger than 4 cm in diameter are more apt to hemorrhage than those smaller than that size. High confidence can also be assigned to those renal masses that exhibit the radiologic analogues for hemangioma with use of imaging modalities that document their vascular nature. These findings should be sufficient for therapeutic decisions directed toward embolization or surgical excision when clinically warranted. If a mass can be characterized as a simple cyst by satisfying all of the required CT or sonographic criteria, no further diagnostic interventions are required. This includes the radiologic findings of thin rim of peripheral calcification and thin septa with or without calcification. An equally high level of confidence is associated with the broad range of CT, sonographic, or MR imaging findings that indicate malignant tumor. These militate for radical surgery. However, the same findings are also encountered in hemorrhagic and infected renal cyst, abscess, benign neoplasms, and inflammatory mass. Therefore, surgical excision, the nature of which will vary according to individual circumstances, is usually required to establish these diagnoses. Exceptions to the need for a tissue diagnosis might be considered in the patient in whom a renal mass is detected in the clinical setting of infection and in the patient with either a small asymptomatic renal mass or a small hyperattenuating mass that meets the other criteria of a simple cyst. Here again, individual circumstances may lead to such alternatives as aspiration of the mass for culture, interval follow-up to seek evidence of growth, or dismissal.

Abscess↗
PubMed1997

Rhabdoid tumor of the kidney in children: a comparative study of 21 cases.

OBJECTIVE: Rhabdoid tumor of the kidney (RTK) is unique among childhood renal neoplasms in its frequent association with primary or metastatic CNS lesions. Previous reports suggest that RTK has characteristic CT features. It has been proposed that if CT could accurately predict the correct diagnosis of RTK preoperatively, then imaging protocols might be modified during the examination to include imaging of the brain. We wished to determine if RTK could be reliably distinguished from other renal neoplasms of early childhood. MATERIALS AND METHODS: We retrospectively reviewed clinical, radiologic, and pathologic records of 21 patients with RTK. The study group included 13 males and eight females who were newborn to 36 months old (mean, 11 months). The study group was compared with 153 patients who were 3 years old or younger and who had solid renal masses. From the comparison group a subset of 54 patients 1 year old and younger was also selected for comparison with 13 (62%) of the 21 patients in the study group who were 1 year old or younger. Both comparison groups consisted of patients whose case material was consecutively added to the radiologic pathology archives at our institution. Diagnoses of the group of 153 patients were Wilms' tumor (n = 93), mesoblastic nephroma (n = 44), clear cell sarcoma of the kidney (n = 12), renal cell carcinoma (n = 3), and undifferentiated sarcoma (n = 1). RESULTS: A prominent eccentric crescent with the attenuation of fluid, representing sub-capsular renal hemorrhage or peripheral tumor necrosis adjacent to tumor lobules, was revealed on CT scans in 15 (71%) of the 21 patients with RTK and in seven (54%) of the 13 patients with RTK who were 1 year old or younger. Nineteen (12%) of 153 patients in the larger comparison group, representing patients with all tumor types, had CT features identical to those of the RTK group, including six (4%) patients with pathologic confirmation of sub-capsular renal hematomas. Six (11%) of the 54 comparison patients 1 year old and younger had CT features identical to those of the RTK group, and all proved to have mesoblastic nephroma. Associated CNS lesions were seen on CT or MR imaging in 11 (52%) of the 21 patients with RTK but none was seen in the comparison group of patients. CONCLUSION: On CT, a peripheral crescent with the attenuation of fluid is characteristic of RTK. However, 12% of renal neoplasms that occur more commonly than RTK in children had CT findings indistinguishable from those of RTK. Because the prevalence of RTK is relatively low, and because the CT findings are not pathognomonic, a renal mass seen on CT in a child is unlikely to represent RTK regardless of its CT features. We therefore conclude that the routine addition of CT of the brain for pediatric patients with renal masses that show a peripheral crescent of fluid attenuation is not justified. Supplemental imaging of the brain should be based on clinical findings or tissue diagnosis.

Brain Neoplasms↗
PubMed1997

The kidney: radiologic-pathologic correlation.

Selected concepts of MR-pathologic correlation of renal masses are presented in this article by way of illustrative examples, with an emphasis on renal adenocarcinoma. Where applicable, practical uses of these concepts are suggested, particularly in those cases in which the differential diagnosis might be narrowed, such as in the evaluation of angiomyolipoma. Also included is a discussion of management decisions that may be affected by the information provided by MR imaging.

Carcinoma, Renal Cell↗
PubMed1997

The adrenal gland: radiologic-pathologic correlation.

The adrenal glands are affected by complex physiologic and neoplastic processes. Recently described computed tomography densitometry and chemical shift MR imaging techniques are useful to distinguish between benign and malignant masses. Knowledge of the basic gross pathologic and histologic correlates of adrenal disease helps in applying these new imaging methods and in understanding established cross-sectional studies.

Adrenal Gland Diseases↗
PubMed1997

Structural determination in AUF1 required for high affinity binding to A + U-rich elements.

AUF1 is a RNA-binding protein that contains two non-identical RNA recognition motifs (RRMs). AUF1 binds to A + U-rich elements (AREs) with high affinity. The binding of AUF1 to AREs is believed to serve as a signal to a mRNA processing pathway which degrades mRNAs encoding many cytokines, oncoproteins and G protein-coupled receptors. Because the ARE-binding activity of AUF1 appears central to the regulation of many important genes, we analyzed the domains of the protein that are important for this activity. Examination of the binding affinity of various mutants indicates that both RRMs may be required for binding. However, they are not sufficient. Highest affinity binding requires an alanine/glycine-rich region of the N-terminus and a short glutamine-rich region in the C-terminus. The N-terminus is required for dimerization of AUF1. However, AUF1 binds an ARE as a hexameric protein. Thus protein-protein interactions are important for high affinity ARE-binding activity of AUF1.

Binding Sites↗
PubMed1996

cDNA cloning of a chick homologue of human ATPase complex subunit 4, quantitative tissue distribution and tertiary structure comparison of the ATPase domain to RecA.

The ocular lens consists of a single layer of epithelial cells on its anterior surface and underlying fiber cells, which are derived from the epithelial cells by differentiation and make up the bulk of the lens. Because lens cells are segregated by age and stage of differentiation, we are using this tissue to study the role of the proteasome in differentiation. The purpose of this study is to corroborate the ATPase function of chick subunit 4 (cS4) and assess the levels of the mRNA in the differentiating lens relative to other tissues. We have generated a computer model of the tertiary structure of the ATPase domain of the cS4 of the ATPase complex that regulates the 20S proteasome. The predicted polypeptide from the cloned cDNA of cS4 (440 residues) had a calculated molecular mass of 49,182 and is 98 and 73% identical to human and yeast S4 protein sequences, respectively. A computer search for comparison with known proteins in GenBank showed that the cS4 protein sequence has a conserved region of about 200 amino acid residues including an ATP/GTP binding site and a mitochondrial energy transfer proteins signature sequence. Based on secondary structure, the computer-generated model of the ATPase domain is comparable to that of RecA, with a root mean square deviation of 0.851 from the RecA triad. mRNA in the 14-day-old chick embryo lens is derived primarily (90%) from differentiating cells. The level of cS4 mRNA determined by quantitative RT/PCR in this differentiating tissue was comparable to the cS4 mRNA levels in chick liver, heart, and brain.

Adenosine Triphosphatases↗
PubMed1996

Localization and physical mapping of genes encoding the A+U-rich element RNA-binding protein AUF1 to human chromosomes 4 and X.

Messenger RNAs encoding many oncoproteins and cytokines are relatively unstable. Their instability, which ensures appropriate levels and timing of expression, is controlled in part by proteins that bind to A+U-rich instability elements (AREs) present in the 3'-untranslated regions of the mRNAs. cDNAs encoding the AUF1 family of ARE-binding proteins were cloned from human and murine cDNA libraries. In the present study monochromosomal somatic cell hybrids were used to localize two AUF1 loci to human chromosomes 4 and X. In situ hybridization analyses using P1 clones as probes identified the 4q21.1-q21.2 and Xq12 regions as the locations of the AUF1 genes.

Animals↗
PubMed1996

Ultrasound versus radiography in the detection of soft-tissue foreign bodies.

STUDY OBJECTIVE: To determine the usefulness of ultrasound and radiography in detecting foreign bodies in soft-tissue models closely duplicating puncture-wound trauma and hand anatomy. METHODS: In this randomized, blinded descriptive study, two radiologists independently evaluated 120 chicken thighs for foreign bodies with the use of standard two-view radiography and 7.5-MHz transducer ultrasonography. All chicken thighs were manipulated with hemostats to ensure uniform tissue damage. In 60 thighs, one foreign body had been inserted (10 each: gravel, metal, glass, cactus spine, wood, and plastic). RESULTS: The sensitivity of ultrasound in detecting gravel was 40%, that for metal was 45%, that for glass was 50%, that for cactus spine was 30%, that for wood was 50%, and that for plastic was 40%. The overall sensitivity, specificity, and false-negative and false-positive rates for ultrasound were 43%, 70%, 50%, and 30%, respectively. No individual foreign body had an ultrasound detection rate of 50%. Radiography detected foreign bodies generally considered radiopaque (gravel, glass, metal) 98% of the time, but it never detected bodies considered radiolucent (wood, plastic, cactus spine). The false-negative and false-positive rates for radiography were 50% and 1.6%, respectively. CONCLUSION: Ultrasound detection of foreign bodies by skilled operators in this animal model revealed poor sensitivity and specificity. Radiographic detection was highly sensitive for foreign bodies considered radiopaque. Our data suggest that ultrasound should not be relied on to rule out the possibility of a retained foreign body in the distal extremities.

Animals↗
PubMed1996

From the archives of the AFIP. Gestational trophoblastic disease: radiologic-pathologic correlation.

Gestational trophoblastic disease (GTD) is a manifestation of an aberrant fertilization event that leads to a proliferative process and, potentially, to an invasive neoplasm. The spectrum of GTD includes hydatidiform moles (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic disease (rare). Increased levels of human chorionic gonadotropin (beta-hCG) are associated with all forms. Ultrasonography (US), performed late in the first trimester of a pregnancy complicated by hyperemesis gravidarum, toxemia, or bleeding, is essential in the early detection of hydatidiform mole, the most common form of GTD (80% of cases). In these cases, US typically reveals a central heterogeneous mass with anechoic spaces, which correspond to hydropic villi. In cases of invasive mole, imaging may show a central uterine process (similar to that seen in noninvasive moles), occasionally with myometrial invasion. Choriocarcinoma is often seen as a mass enlarging the uterus, with a heterogeneity that correlates with necrosis and hemorrhage. Because of the widespread availability of serum measurement of beta-hCG, diagnosis of the more severe, persistent manifestations of GTD seldom depends on radiologic examinations. However, imaging studies may alert the referring physician to the diagnosis in cases of early disease. Also, imaging studies may have a problem-solving role in examining patients with recurrent GTD or a confusing clinical picture.

Brain Neoplasms↗
PubMed1995

Age-dependent association of isolated bovine lens multicatalytic proteinase complex (proteasome) with heat-shock protein 90, an endogenous inhibitor.

The multicatalytic proteinase complex (MPC) (proteasome) is a high-molecular-weight proteolytic enzyme found in eukaryotic cells and archaebacteria. Regulatory proteins that inhibit or activate the MPC have been described. Association with an ATPase complex alters the specificity of the multicatalytic proteinase complex to permit cleavage of ubiquitinylated proteins. Unidentified proteins have been observed in highly purified preparations of the multicatalytic proteinase complex. Based on immunoreactivity and N-terminal sequencing, we have identified heat-shock protein 90 as a major component of the multicatalytic proteinase complex prepared from 1-month, but not 2-year bovine lenses. alpha-Crystallin, a lens structural protein with chaperone activity, is also found in multicatalytic proteinase complex preparations. Both heat-shock protein 90 and alpha-crystallin inhibit hydrolysis of Cbz-Leu-Leu-Leu-MCA by the multicatalytic proteinase complex at a stoichiometry of 1 mol heat-shock protein per mole of MPC. Heat-shock proteins may interact with denatured proteins and facilitate their degradation. These studies give evidence for the involvement of heat-shock proteins in proteolysis by direct interaction with the multicatalytic proteinase complex.

Age Factors↗
PubMed1995

D20S16 is a complex interspersed repeated sequence: genetic and physical analysis of the locus.

The genomic structure of the D20S16 locus has been evaluated using genetic and physical methods. D20S16, originally detected with the probe CRI-L1214, is a highly informative, complex restriction fragment length polymorphism consisting of two separate allelic systems. The allelic systems have the characteristics of conventional VNTR polymorphisms and are separated by recombination (theta = 0.02, Zmax = 74.82), as demonstrated in family studies. Most of these recombination events are meiotic crossovers and are maternal in origin, but two, including deletion of the locus in a cell line from a CEPH family member, occur without evidence for exchange of flanking markers. DNA sequence analysis suggests that the basis of the polymorphism is variable numbers of a 98-bp sequence tandemly repeated with 87 to 90% sequence similarity between repeats. The 98-bp repeat is a dimer of 49 bp sequence with 45 to 98% identity between the elements. In addition, nonpolymorphic genomic sequences adjacent to the polymorphic 98-bp repeat tracts are also repeated but are not polymorphic, i.e., show no individual to individual variation. Restriction enzyme mapping of cosmids containing the CRI-L1214 sequence suggests that there are multiple interspersed repeats of the CRI-L1214 sequence on chromosome 20. The results of dual-color fluorescence in situ hybridization experiments with interphase nuclei are also consistent with multiple repeats of an interspersed sequence on chromosome 20.

Alleles↗
PubMed1995

Intracranial vascular malformations.

Intracranial vascular malformations are nonneoplastic developmental anomalies that present a variety of clinical patterns, ranging from asymptomatic to fatal intracranial hemorrhage. A practicing radiologist can expect to encounter these abnormalities, which include capillary telangiectasias, venous angiomas (also called developmental venous anomalies), cavernous angiomas, and arteriovenous malformations. The imaging findings that characterize these lesions are reviewed in this article, along with their pathological and clinical features.

Brain↗
PubMed1995

Multilocular cystic renal tumor in children: radiologic-pathologic correlation.

Multilocular cystic renal tumor is a term that encompasses two histologically distinct but grossly indistinguishable lesions: cystic nephroma and cystic partially differentiated nephroblastoma (CPDN). Cystic nephroma is a segmental, purely cystic mass characterized by multiple septations composed entirely of differentiated tissues, without blastemal elements. CPDN is also a multiloculated lesion without nodular solid components, but its septa contain embryonal cells. Multilocular cystic tumors primarily affect boys during early childhood, with a substantial number of the lesions containing blastema (CPDN), and adult women, with lesions that more commonly lack septal blastema (cystic) nephroma). As a rule, nephrectomy is curative and the clinical course benign, but CPDN may recur locally. Although cystic nephroma and CPDN cannot be distinguished radiologically, failure to do so has no practical impact on management, since all of these tumors are surgically removed. However, the differential diagnosis includes other pediatric cystic renal masses that may require different treatment stratagems: Wilms tumor with cyst formation due to hemorrhage and necrosis, cystic clear cell sarcoma, cystic mesoblastic nephroma, cystic renal cell carcinoma, multicystic dysplastic kidney, and segmental multicystic dysplasia in a duplicated renal collecting system.

Adolescent↗
PubMed1994

Characterization of cDNAs encoding the murine A+U-rich RNA-binding protein AUF1.

A+U-rich elements (ARE) serve to control the degradation of some proto-oncogene and lymphokine mRNAs. The protein, AUF1, which consists of two polypeptides of 37 and 40 kDa (p37 and p40, respectively) when purified from cytosol, has been implicated in ARE-directed mRNA turnover due to its binding to ARE. Molecular cloning of a cDNA (p37AUF1) corresponding to human p37 predicted a polypeptide containing two non-identical RNA recognition motifs (RRM) and a C-terminal Gln-rich domain [Zhang et al. Mol. Cell. Biol. 13 (1993) 7652-7665]. Two cDNAs, designated muAUF1-3 and muAUF1-7, were isolated from a murine fetal cDNA library, using as a probe, a fragment of the p37AUF1 cDNA encoding RRM1 and approximately half of RRM2. The muAUF1-3 open reading frame (ORF) was very homologous to human p37AUF1 with the greatest homology between the corresponding RRMs and the C-terminal Gln-rich motif. Clone muAUF1-7 was highly homologous to muAUF1-3, but was truncated within the region encoding the RNP-1 box in RRM2. Clone muAUF1-3 encoded 19 amino acids in RRM1 not encoded by either muAUF1-7 or human p37AUF1. Such alterations in sequence could modify the RNA-binding properties of these proteins and have concomitant effects on ARE-directed posttranscriptional processes.

Adenine↗
PubMed1994

Magnetic resonance evaluation of congenital uterine anomalies.

Congenital malformations of the uterus (also known as müllerian duct anomalies) exist as a spectrum of disorders; each of these, to some extent, is associated with reproductive dysfunction. Significant improvements in imaging methods such as ultrasound and magnetic resonance have the potential to eliminate the need for invasive evaluation of patients with suspected uterine anomalies. This article reviews the relevant embryology and classification of müllerian duct anomalies as well as the relationship between the imaging features and general therapeutic options.

Congenital Abnormalities↗
PubMed1994

From the archives of the AFIP. Ovarian epithelial neoplasms: radiologic-pathologic correlation.

Ovarian carcinoma is the most common cause of death from a gynecologic malignant neoplasm. The typically advanced stage at presentation and aggressive nature of these neoplasms result in an overall 5-year survival rate of less than 40%. Most malignant ovarian neoplasms are of the surface epithelial cell type, which includes serous, mucinous, clear cell, endometrioid, and Brenner tumors. However, among the epithelial neoplasms, benign lesions are more common than malignant neoplasms, and other entities (including nonneoplastic masses) are far more common causes of a pelvic mass. Imaging studies (ultra-sound, computed tomography, and magnetic resonance imaging) can depict the tumor morphology: solid or cystic, unilocular or multilocular cystic, with or without thickening of the walls or septa, with or without papillary excrescences or other soft-tissue elements, and with or without calcifications. Evaluation of these morphologic characteristics allows attempted differentiation among malignant, benign neoplastic, and nonneoplastic lesions. Lesion characterization assists in surgical planning. Malignant neoplasms nearly always require laparotomy, whereas benign neoplasms may be managed laparoscopically. In the case of ovarian carcinoma, treatment is primarily surgical, and most patients also receive chemotherapy. Unfortunately, recurrence is common.

Adult↗