Imaging protocol for suspected ureteric calculi in patients presenting to the emergency department.

AIM: To ensure diagnostic yields were adequate in patients with suspected ureteric calculi with and without haematuria, and to assess whether there was a significant difference between these two groups in men and women. MATERIALS AND METHODS: A retrospective analysis was undertaken of 513 patient records who attended the Emergency Department with suspected ureteric colic over 8 months. RESULTS: 513 patient records were evaluated. The overall positive rate for calculi was 45.4%, with an alternative diagnosis in 14.4%. Of the patients scanned with haematuria 49.36% were positive. The positive scan rate in males was significantly higher than in females (56% v. 31%, p < 0.0001). 32.79% of patients scanned without haematuria had a proven calculus. The positive rate in males without haematuria was 40.39% versus 27.14% in females. CONCLUSION: The overall diagnostic yield of 45.4% is acceptable according to national guidelines. A large number of patients scanned without haematuria were found to have a calculus. This review suggests that in males a negative urine dipstick should not preclude CT investigation for renal colic in the presence of a "classical" history. However, the number of female patients with negative scans suggests that further randomized studies are needed to identify the ideal investigation pathway in women.

Management of acute non-cirrhotic and non-malignant portal vein thrombosis: a systematic review.

BACKGROUND: No definitive evidence exists regarding the treatment of acute portal vein thrombosis (PVT). Treatment modalities described include conservative management, anticoagulation, thrombolysis, and thrombectomy. This review examines the impact of such treatment, its outcomes, and the complications resulting from the resultant portal hypertension. METHODS: A Medline literature search was undertaken using the keywords portal vein thrombosis, anticoagulation, thrombolysis, and thrombectomy. The primary end point was portal vein recanalization. Secondary outcome measures were morbidity and the development of portal hypertension and its sequelae, including variceal bleeding. Data from articles relating to PVT in the context of cirrhosis, malignancy, or liver transplant were excluded. RESULTS: Early systemic anticoagulation results in complete portal vein recanalization in 38.3% of cases and partial recanalization in 14.0% of cases. Spontaneous recanalization without treatment can only be expected in up to 16.7% of patients. Frequently this is only when associated with self-limiting underlying pathology and/or minimal thrombus extension. Thrombolysis can be associated with major complications in up to 60% of patients. CONCLUSIONS: The natural history of acute PVT is poorly described. Spontaneous resolution of acute portal vein thrombosis is uncommon. Early anticoagulation results in a satisfactory rate of recanalization with minimal procedure-associated morbidity. Thrombolysis should be used with caution and only considered if the disease is progressive and signs of mesenteric ischemia are present. Further well-designed trials with precise outcome reporting are needed to improve our understanding of the disease.

Transport and phosphorylation as factors in the antitumor action of cytosine arabinoside.

Survival of mice bearing different transplantable leukemias and treated with cytosine arabinoside was compared with uptake and subsequent phosphorylation of the drug in vitro. Capacity for nucleotide formation was correlated with response and is apparently an important determinant of drug sensitivity. Drug uptake, although apparently mediated, was similar in all cell lines.

Nucleotide formation as a determinant of 5-Fluorouracil response in mouse leukemias.

Survival of mice bearing different transplantable leukemias and treated with 5-fluorouracil was compared with accumulation of drug nucleotides in vitro. There was significant correlation,suggesting that cellular capacity for conversion of the drug to nucleotides is a major determinant of inherent drug sensitivity of these leukemias.

Phaseolin gene from bean is expressed after transfer to sunflower via tumor-inducing plasmid vectors.

Sequences coding for the bean seed protein phaseolin were inserted into transferred DNA regions of tumor-inducing plasmids. Constructions were devised in which the coding region of phaseolin was fused in the correct reading frame with the coding region of octopine synthase and placed under the transcriptional control of the octopine synthase promoter. Other plasmids were prepared to permit expression of the phaseolin-encoding sequences from the flanking phaseolin promoter region. The RNA transcribed in sunflower cells transformed with these constructions was characterized by hybridization procedures, SI nuclease mapping, and by translation in vitro of extracted RNA. These tests showed that the genomic intervening sequences were correctly excised. Immunoreactive phaseolin polypeptides were detected by enzyme-linked immunosorbent assay and by antibody hybridization to electrophoretically separated protein extracts of sunflower tissues isolated from crown gall tumors and of transformed sunflower cells grown in tissue culture. These results demonstrate the expression of a plant gene after transfer to a taxonomically distinct botanical family.

Bioassay procedure for the detection of mutagenic metabolites in human urine with the use of sister chromatid exchange analysis.

A short-term bioassay system for the detection of activated mutagenic metabolites in urine from humans exposed to promutagens was described. Human diploid fibroblasts were grown in medium containing 5--20% urine from smokers, from nonsmokers, and from individuals undergoing cyclophosphamide (Cp) chemotherapy for treatment of cancer. The cells were then subjected to sister chromatid exchange (SCE) analysis. Activated Cp metabolic products in urine specimens produced up to a ten-fold increase in SCE's over preinjection SCE levels for the same individuals. Linear dose-response curves over a urine concentration range from 5 to 20% in culture medium were obtained from cells grown in urine specimens from 7 nonsmokers and 8 cigarette smokers. This test system proved to be sensitive to ambient exposure levels of environmental mutagens and demonstrated that urine from smokers was significantly more mutagenic than was urine from nonsmokers. Replicate experiments showed highly reproducible SCE values for each individual as well as for average SCE values for each group of subjects. The ability of this bioassay system to detect trace mutagenic activity in human urine reproducibly makes it an attractive choice for the monitoring of humans who have been exposed to environmental and/or industrial mutagens.

Anthracycline immunoconjugates prepared by a site-specific linkage via an amino-dextran intermediate carrier.

Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per molecule of immunoglobulin G. Flow-cytometric studies revealed the retention of the antibody-binding activity. The immunoconjugate was cytotoxic to the target cells, as examined by the 75selenomethionine incorporation studies, and remained efficient for targeting a human colonic tumor (GW-39) in the nude mouse model. The conjugate possessed a greater antitumor activity against the subcutaneous tumor than either the free drug or an irrelevant antibody conjugate, and it was well tolerated by the animals at a much higher dose level than was the unconjugated drug.

Clinical studies of cancer radioimmunodetection with carcinoembryonic antigen monoclonal antibody fragments labeled with 123I or 99mTc.

Seventy-three patients with diverse cancers containing carcinoembryonic antigen received 123I-labeled anti-carcinoembryonic antigen monoclonal antibody F(ab')2 fragment [38 patients], 99mTc-labeled anti-carcinoembryonic antigen monoclonal antibody Fab' fragment [23 patients], or both reagents at different times [6 patients] for evaluation of antibody targeting and imaging [radioimmunodetection (RAID)], using planar and single-photon emission computed tomography. The results indicated that antibody fragments are preferred for early tumor imaging (within 24 h). Rapid targeting and clearance from blood and normal organs of the antibody fragments (blood median t1/2 elimination of 26.5 and 13.2 h for the F(ab')2 and Fab' fragments respectively) permitted the use of short-lived radionuclides, such as 123I (13.3 h) and 99mTc (6 h), and confirmed that selective antibody accretion in tumors occurred very soon after administration, such as between 2 and 5 h. Scan interpretations at 24 h for the 123I-labeled F(ab')2 and at 2-5 h for the 99mTc-labeled Fab' revealed overall sensitivities, on a tumor site basis, of 95.9 and 94.9%, respectively. On a site basis, the overall accuracies were 94.2 and 93.8% for the 123I and 99mTc immunoconjugates, respectively. In the 6 patients studied with both radioimmunoconjugates, a high concordance in detection was found. Both imaging agents also revealed a high number of putatively new tumor sites not disclosed by other radiological methods at the time of the RAID studies, of which 40.0 and 20.5% were subsequently confirmed as tumor for the 123I and 99mTc agents, respectively, within an 11-month follow-up period. This represented 24 proven occult tumor sites in 19 patients given the 123I-immunoconjugate and 16 proven occult tumor sites in 9 patients receiving the 99mTc agent. The new lesions were found up to 17 and 7 months earlier for 123I-RAID and 99mTc-RAID, respectively, than with other detection methods. The smallest tumors identified were below 0.5 cm, especially with the 99mTc immunoconjugate and single-photon emission computed tomography imaging. The findings of this study confirm previous evidence that RAID is a safe and a potentially useful new method of cancer detection. Despite the excellent results with the 123I-F(ab')2 antibody fragment, its poor availability and high cost limit its clinical use. Therefore, the 99mTc agent, which is made by an instant, 1-step, 1-vial, direct labeling method, appears to be the method of choice for rapid and accurate detection of cancer by RAID.

Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody.

Sixteen patients with non-Hodgkin's lymphoma were infused with 6.2 to 58.2 mCi (0.2 to 3.9 mg) doses of radioactive iodine (131I)-labeled LL2 immunoglobulin G (IgG) or F(ab')2, in order to study antibody distribution, pharmacokinetics, dosimetry, toxicity, tumor targeting, and therapy. LL2 is a murine IgG2a monoclonal antibody (MAb) reactive with B cells and non-Hodgkin's B-cell lymphoma. In a series of five assessable therapy patients, doses as small as 30 mCi 131I-LL2 IgG or F(ab')2 resulted in tumor responses (two partial remissions, two mixed and minor responses, and one no response), while one patient receiving diagnostic doses as low as 6.2 mCi showed a partial remission for 1 year and a complete remission after a second low radiation dose. No acute toxicities were noted, and only myelotoxicity accompanied therapeutic doses, with grade IV marrow toxicity seen in three of seven patients receiving total doses of about 50 mCi. Dosimetry calculations showed spleen and tumor dose rules of about 4.6 cGy/mCi, which was three to four times the dose to other organs. Despite the administration of relatively low doses of LL2 (0.2 to 3.9 mg), 82% of 60 known extrasplenic lymphoma sites were imaged. Serum clearance showed an average distribution half-life (T1/2) of 2.1 hours and an elimination T1/2 of 32.0 hours. The average total-body clearance T1/2 was 43 to 45 hours. LL2's antigenic target does not appear to be shed in high amounts into the circulation. Three of eight patients having at least two injections showed a human antimouse antibody response. These patients may have been presensitized to animal protein. An interesting observation in this study was the marked drop in circulating B lymphocytes after the administration of radioiodinated LL2 or anticarcinoembryonic antigen MAbs, suggesting that this is a nonspecific radiation effect and not necessarily related to the binding of MAb to normal B cells.

Mutational analysis of the sequence and structural requirements in brome mosaic virus RNA for minus strand promoter activity.

An RNA-dependent RNA polymerase (replicase) activity that specifically copies brome mosaic virus (BMV) RNAs in vitro can be prepared from BMV-infected barley leaves. The signals directing complementary (minus) strand synthesis reside within the 3' 134-nucleotide-long tRNA-like structure that is common to each of the virion RNAs. By studying the influence of minus strand synthesis of numerous mutations introduced throughout this region of the RNA, we have mapped in detail the sequence and structural elements necessary for minus strand promoter activity. Sequence alterations (either substitutions or small, structurally discrete deletions) in most parts of the tRNA-like structure resulted in decreased minus strand synthesis. This suggests that BMV replicase is a large enzyme, possibly composed of several subunits. The lowest activities, 5 to 8% of wild type, were observed for mutants with substitutions at three separate loci, identifying one structural and two sequence-specific elements essential for optimal promoter activity. (1) Destabilization of the pseudoknot structure in the aminoacyl acceptor stem resulted in low promoter activity, demonstrating the importance of a tRNA-like conformation. (2) Substitution of the C residue adjacent to the 3' terminus resulted in low promoter activity, probably by interfering with strand initiation. (3) The low activities resulting from substitutions and a small deletion in arm C suggest this region of the RNA to be a major feature involved in replicase binding. In particular, nucleotides within the loop of arm C appear to be involved in a sequence-specific interaction with the replicase.

Mutational analysis of the tRNA mimicry of brome mosaic virus RNA. Sequence and structural requirements for aminoacylation and 3'-adenylation.

The genomic RNAs of brome mosaic virus (BMV) exhibit various tRNA-like properties, including specific tyrosylation by tyrosyl-tRNA synthetases and adenylation of the 3'-CCOH derivative by tRNA nucleotidyl transferases. We have studied the effect of numerous mutations in all domains of the tRNA-like structure of BMV RNA on tyrosylation and adenylation in vitro. Surprisingly few mutations resulted in more than 50% decrease in tyrosylation rates with either wheat germ or yeast synthetases; those mutations were at the 3' terminus, the pseudoknot, and the bases of arms B and E. The results suggest an interaction of synthetase with arm A as the analog of the aminoacyl acceptor stem of tRNAs, and arm B as the analog of the anticodon arm of tRNAs, although there is no apparent interaction with the terminal loop of arm B analogous to the interaction with the anticodon in tRNAs. Mutations at several loci resulted in large losses of adenylation activity catalyzed by wheat germ and Escherichia coli nucleotidyl transferases; those loci were the pseudoknot, the bases of arms B, C and D, and at the junctions of these arms with arm A. These studies have identified mutants specifically defective in one of the tRNA-like activities, which are appropriate for investigating the role of these activities during infection in vivo.

Replication in vivo of mutant brome mosaic virus RNAs defective in aminoacylation.

In order to understand the relationship between replication and aminoacylation of the genomic RNAs of brome mosaic virus, the replication of four mutants, whose RNAs were expected (on the basis of their properties in vitro) to be inefficiently tyrosylated in vivo, was studied in barley protoplasts and plants. Test inocula consisted of capped transcripts of wild-type RNAs 1 and 2, and of RNA 3 variants with defined mutations in the 3' tRNA-like region. Mutant 5'PsK, which is defective in minus-strand promoter activity and a poor substrate in vitro for both tyrosylation and 3' adenylation, replicated in protoplasts to 20% of wild-type even though only about 6% of the progeny molecules had correct 3' termini that would permit tyrosylation. Mutant psi GG, which is defective in vitro for 3' adenylation and minus-strand promoter activities but accepts tyrosine at near-normal rates, replicated to 40% of wild-type in protoplasts although only 15% of the progeny molecules had correct 3' termini. Two other mutants (delta 5' and 5'AGA), with 20-fold lower rates of tyrosylation in vitro than wild-type RNA, replicated to 60 to 70% of wild-type levels in protoplasts and gave similar yields to wild-type in systemic infections of plants. All mutant sequences were preserved in progeny RNAs, indicating that no recombination between homologous 3' ends occurred. The 40% reduction of replication in protoplasts seen for mutant delta 5', whose only known functional lesion is depressed tyrosylation in vitro, may indicate that an indirect role for aminoacylation exists. However, the results obtained argue against an obligatory role for tyrosylation in RNA replication in vivo.

Minus-strand initiation by brome mosaic virus replicase within the 3' tRNA-like structure of native and modified RNA templates.

An RNA-dependent RNA polymerase (replicase) extract from brome mosaic virus-infected barley leaves has been shown to initiate synthesis of (-) sense RNA from (+) sense virion RNA. Initiation occurred de novo, as demonstrated by the incorporation of [gamma-32P]GTP into the product. Sequencing using cordycepin triphosphate to terminate (-) strands during their synthesis by the replicase generated sequence ladders that confirmed that copying was accurate, and that initiation occurred very close to the 3' end. The precise site of initiation was further defined by testing the replicase template activity after stepwise removal of 3'-terminal nucleotides. Whereas removal of the terminal A did not decrease template activity, removal of the next nucleotide (C-2) did. Thus, initiation almost certainly occurs opposite the penultimate 3'-nucleotide (C-2) in vitro. The structure of the double-stranded replicative form of RNA isolated from brome mosaic virus-infected leaves was consistent with such a mechanism occurring in vivo, in that it lacked the 3'-terminal A found on virion RNAs. The specific site of (-) strand initiation and normal template activity were retained for RNAs with as many as 15 to 30 A residues added to the 3' end. However, only limited oligonucleotide 3' extensions can be present on active templates. In order to assess the 5' extent of sequences required for an active template, a 134-nucleotide-long fragment of brome mosaic virus RNA, corresponding to the tRNA-like structure, was generated. This RNA had high template activity, but a shorter 3' (85-nucleotide) fragment was inactive. RNAs with various heterologous sequences 5' to position 134 also showed high template activity. Thus, the 3'-terminal tRNA-like structure common to all four brome mosaic virus virion RNAs contains all of the signals required for initiation of replication, and sequences 5' to it do not play a role in template selection.

Rice Triosephosphate Isomerase Gene 5[prime] Sequence Directs [beta]-Glucuronidase Activity in Transgenic Tobacco but Requires an Intron for Expression in Rice.

In rice (Oryza sativa L.), cytosolic triosephosphate isomerase (TPI) is encoded by a single gene. TPI catalyzes a vital step in glycolysis, and RNA blots showed that the tpi gene is expressed in all vegetative tissues (root, culm, and leaves) and in rice suspension cells. No effect of light on expression was detected, but submergence of rice seedlings resulted in elevated levels of TPI mRNA in roots and culms. The 2767-bp 5[prime] upstream sequence of the tpi gene was fused translationally with the [beta]-glucuronidase (gusA) gene, and the resulting construct, TPI-GUS, was found to express constitutive, high levels of GUS activity in transgenic tobacco (Nicotiana tabacum) plants. However, the same construct yielded no GUS activity in stably transformed rice plants, and RNA blots showed that no GUS mRNA could be detected even though stable integration of functional copies of the construct was confirmed by Southern blot and genomic polymerase chain reaction analyses. Transient assays using particle bombardment yielded high levels of GUS expression from the TPI-GUS construct in tobacco leaves, but essentially no expression in rice, barley, or maize leaves. When the first intron of the tpi gene was included in the construct (TPI-int1-GUS), transient GUS activity was routinely obtained in rice leaves, revealing that the first intron of the rice tpi gene is crucial for its expression in rice. TPI-int1-GUS also directed transient GUS expression in maize and barley leaves, but little or no activity was obtained from this construct in tobacco, tomato, or soybean leaves. These results with the rice tpi promoter are in accordance with mounting evidence that differences in gene expression exist between monocots and dicots.

Cell Ablation Reveals That Expression from the Phaseolin Promoter Is Confined to Embryogenesis and Microsporogenesis.

Most previous studies of the [beta]-phaseolin (phas) gene, which encodes the major storage protein in bean (Phaseolus vulgaris L.), have shown its expression to be rigorously confined to the developing seed, both in bean and transgenic tobacco (Nicotiana tabacum L. cv Xanthi) plants. To confirm unequivocally the lack of phas expression in vegetative tissues, we placed the diphtheria toxin A-chain (DT-A) coding region under the control of [beta]-phaseolin promoter sequences. Tobacco plants transgenic for phas/DT-A were phenotypically normal until flowering, when they produced anthers that were externally normal but contained no viable pollen. Microscopic examination of immature anthers revealed a normal tapetum, but the pollen mother cells did not undergo meiosis and subsequently degenerated, resulting in male-sterile plants. This demonstration of phas expression during microsporogenesis was corroborated by the expression of [beta]-glucuronidase in pollen of plants transformed with comparable phas/uidA constructs. Although these findings suggested that similarities in phas expression may exist between seed and pollen maturation, no phas activity could be detected in bean pollen. After fertilization of the DT-A-transformed plants with pollen from wild-type tobacco, 50% of the resulting embryos aborted at the heart stage, defining this as the earliest time for phas expression during embryogenesis.

Is Abdominal Fat Distribution Measured by Axial CT Imaging an Indicator of Complications and Mortality in Acute Pancreatitis?

BACKGROUND: Obesity is an important risk-stratifying co-morbidity for many pathological conditions. Controversy exists about its influence in outcomes after acute pancreatitis (AP). This study assessed abdominal fat distribution (subcutaneous, retroperitoneal and intra-abdominal) measured using computer tomography (CT) images and related it to outcomes in patients with AP. METHODS: The case notes of patients admitted with AP were identified from computerised records from 2008 to the 2013. Image analysis software was used to assess the individual abdominal fat distributions from CT images. RESULTS: A total of 79 patients were included. There was no relationship between fat distribution and either severity of, or mortality from, AP. Fat distribution was not found to be an independent risk factor on multivariate analysis. There was, however, a positive correlation between retroperitoneal and intra-abdominal fat with APACHE II scores, Ranson and Glasgow score and Multiple Organ Dysfunction score (MODS) on various days following admission (r = 0.421, p = 0.0008; r = 0.469, p < 0.0001; r = 0.398, p = 0.007; r = 0.336, p = 0.011, respectively). On multiple logistical regression analysis, the only variables associated with mortality were Balthazar Severity Index, MODS and EWS with a p value of <0.0001, 0.0019 and 0.0481, respectively. CONCLUSIONS: Obese patients have worse predicted outcomes as measured by the EWS, MODS and Ranson scores. Abdominal fat distribution, however, was not shown to be directly related to AP severity or mortality. The addition of fat parameters may be of use in prognostic CT severity index models, but from this data, it does not appear to be an independent risk factor of adverse outcome.

Virus recovery is induced in Brome mosaic virus p2 transgenic plants showing synchronous complementation and RNA-2-specific silencing.

Nicotiana benthamiana plants expressing Brome mosaic virus (BMV) p2 protein complemented replication of RNAs1 + 3 but, surprisingly, supported little or no replication of RNA-2. Despite this, the p2 transgenic plants were able to support systemic migration of RNAs-1 and -3. Kinetic analyses showed identical degradation rates for RNAs-2 and -3, greatly detracting from the concept of an induction of an RNA-2-specific degradation system. Deletion analysis identified a 200-nucleotide sequence that may contribute to silencing in a context-specific manner. When R1 progeny of a severely silencing p2 transgenic line were tested for virus resistance, three different classes of reactions were observed. In class 1 and class 3 plants, the virus moved systemically and showed various extents of RNA-2 silencing. However, in class 2 plants, there was a stochastic onset of post-transcriptional silencing in the systemic leaves that was reminiscent of virus recovery. Plants showing recovery tended to have a greater number of transgene loci than did those exhibiting component-specific silencing. The induction of silencing did not appear to be dependent solely on the combined steady state levels of the transgene and viral RNA. Some plants transformed with a p2 frameshift construct showed a complete silencing phenotype, but none showed RNA-2-specific silencing. While the relationship between the two types of silencing remains unclear, we speculate that our observations reflect early events in the induction of virus recovery.

Paraneoplastic syndromes: mechanisms.

Neoplasms may affect distant host tissues, but they always involve normal physiologic mechanisms. Van R. Potter said that "Oncogeny is blocked ontogeny," so tumors are committed to their organ anlagen. Paraneoplastic mediators are appropriate to their blocked anlagen stages. Mediators may have autocrine, paracrine, or endocrine actions. However, their release and distribution depend on the mode of cell death, and the spatial relations to host vascularity. Invasiveness and metastasis are means of normal embryonic development, and not new cancer-specific properties. Nor do human cancers acquire new foreign genetic information; thus, they cannot express neoantigens nor be recognized by the host. However, tumors breach the blood-brain barrier and basement membrane separations of ectoderm from mesenchyme and release "forbidden" self-antigens, to which host immunocytes may respond causing cell- and antibody-mediated autoimmunity. This can damage normal host tissues by a "bystander" effect. Paraneoplastic mechanisms can also be analyzed as arising from three-way interactions between cells blocked in ontogeny, their molecular messengers, and the host tissues they target.

Imaging of colorectal carcinoma with radiolabeled antibodies.

Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular study, almost all investigators have observed the disclosure of occult neoplasms by RAID; and (9) RAID, a more functional test of usually high specificity, can complement other radiological methods, such as computed tomography scans, which are limited to structural information.

Common replication strategies emerging from the study of diverse groups of positive-strand RNA viruses.

Studies using brome mosaic virus (BMV), Sindbis virus and poliovirus have provided evidence that disparate groups of plant and animal positive strand RNA viruses have remarkably similar replication strategies. The conservation of several functional domains within virus-encoded nonstructural proteins implies that, although the precise character of these and interacting host components varies for each virus, they employ similar mechanisms for RNA replication. For (+) strand replication, similarities in cis-acting sequence motifs and RNA secondary structures within 5' termini of genomic (+) strands have been identified and have been shown to participate in binding of host factors. The model presented for replication of BMV RNA suggests that binding of these factors to internal control region (ICR) sequence motifs in the double-stranded replication intermediate releases a single-stranded 3' terminus on the (-) strand that may be essential for initiation of genomic (+) strand synthesis. ICR sequences internal to the BMV genome were also found to be required for efficient replication. Asymmetric production of excess genomic (+) over (-) strand RNA, characteristic of all (+) strand viruses, may be accomplished through transition of the replicase from competence for (-) to (+) strand synthesis by the recruitment of additional host factors.