Incidence of spinal disease and role of spinal radiotherapy in multiple myeloma.

Background: Spinal disease (spd) in multiple myeloma (mm) can be a major source of morbidity in newly diagnosed patients and long-term survivors. We retrospectively assessed the incidence of spinal disease in patients newly diagnosed with myeloma, its effect on survival, and the possible effect of spinal radiation therapy (rt). Methods: Patients diagnosed with mm between 2010 and 2014 were identified through the provincial cancer registry. Plain radiography, computed tomography, and magnetic resonance imaging were reviewed to detect and document the type of spd. Data related to rt and systemic therapy were collected. Kaplan-Meier and time-varying Cox regression models were used to describe overall survival. Results: Of 306 identified patients with newly diagnosed mm, 51% had spd, including 17% with lytic disease, 68% with compression fractures, and 15% with spinal cord compression. Of the patients with spd, 61% received spinal rt. Of those patients, 84% received spinal rt within 3 months after their diagnosis. Median dose was 20 Gy. Most patients (89.2%) received chemotherapy, and 22.5% underwent autologous stem-cell transplantation. Only 6 of the patients treated with spinal rt received re-irradiation to the same site. Overall survival was similar for patients with and without spd. On multivariate analysis, spinal rt had no effect on survival. Conclusions: In patients newly diagnosed with mm, spd is a common presentation. With current systemic therapy, the presence of spd had no adverse effect on overall survival. The effect of spinal rt on overall survival was nonsignificant.

The Ask-Upmark kidney: a curable cause of hypertension in young patients.

We are reporting a case of arterial hypertension in a young woman who had an atrophic kidney with a cortical groove and histological features of the Ask-Upmark kidney. Her hypertension was renin dependent and the patient was cured following nephrectomy. Controversy on the pathogenesis of this clinical entity is briefly reviewed.

The degree of ST-segment depression on symptom-limited exercise testing: relation to the myocardial ischemic burden as determined by thallium-201 scintigraphy.

This study sought to determine the relation between the magnitude of exercise-induced ST depression and the ischemic burden as determined by quantitative thallium-201 scintigraphy. One hundred forty-four consecutive patients were prospectively studied with symptom-limited exercise testing and thallium-201 scintigraphy. Of these patients, 37 had between 1.0 and < 2.0 mm (group 1) and 17 had > or = 2.0 mm (group 2) of exercise-induced ST depression. There were no significant differences between groups 1 and 2 with respect to all exercise parameters including peak exercise heart rate (134 +/- 21 vs 144 +/- 26 beats/min), metabolic equivalents achieved (7.9 +/- 3.0 vs 8.6 +/- 3.3), and exercise time (7.4 +/- 2.7 minutes in both groups). There was no significant difference in the prevalence of thallium-201 redistribution defects in group 1 versus group 2 patients (17 of 37 [46%] vs 8 of 17 [47%]), and in the extent of ischemia as determined by the number of redistribution defects per patient (1.2 +/- 1.8 vs 1.2 +/- 1.5, respectively). Thus, in this consecutive group of patients with exercise-induced ST depression, those with > or = 2.0 mm of ST depression, relative to patients with a lesser degree of ST depression, had comparable exercise capacity and comparable ischemic burden by thallium-201 scintigraphic assessment. We conclude that the magnitude of ST depression on symptom-limited exercise testing does not correlate with the extent of ischemia as assessed by quantitative thallium-201 scintigraphy.

Celebration: AHRA (American Healthcare Radiology Administrators) 15th anniversary. Commentary.

Managers constantly strive to improve; it's an inherent goal of the job. Each of the three articles in this section contains valuable information designed to help the manager think, act or even just imagine.

Caution: speed ahead--rare earth imaging systems.

New faster imaging systems present intensified control problems in image quality. The rare eath imaging system can provide adequate resolution at a great reduction in patient dosage. Analysis of all factors involved in screen imaging is necessary to assure correct implementation of the rare earth system.

CtrA mediates a DNA replication checkpoint that prevents cell division in Caulobacter crescentus.

Coordination of DNA replication and cell division is essential in order to ensure that progeny cells inherit a full copy of the genome. Caulobacter crescentus divides asymmetrically to produce a non-replicating swarmer cell and a replicating stalked cell. The global response regulator CtrA coordinates DNA replication and cell division by repressing replication initiation and transcription of the early cell division gene ftsZ in swarmer cells. We show that CtrA also mediates a DNA replication checkpoint of cell division by regulating the late cell division genes ftsQ and ftsA. CtrA activates transcription of the P(QA) promoter that co-transcribes ftsQA, thus regulating the ordered expression of early and late cell division proteins. Cells inhibited for DNA replication are unable to complete cell division. We show that CtrA is not synthesized in pre-divisional cells in which replication has been inhibited, preventing the transcription of P(QA) and cell division. Replication inhibition prevents the activation of the ctrA P2 promoter, which normally depends on CtrA phosphorylation. This suggests the possibility that CtrA phosphorylation may be affected by replication inhibition.

Ordered expression of ftsQA and ftsZ during the Caulobacter crescentus cell cycle.

The mechanisms by which bacterial cell division and DNA replication are co-ordinated are still unknown. We have used the easily synchronizable bacterium Caulobacter crescentus to determine when the cell division genes ftsQ and ftsA are transcribed during the DNA replication cycle and to compare their transcription with that of ftsZ. Unlike the situation in Escherichia coli, transcription of ftsQ and ftsA does not extend into ftsZ in Caulobacter. ftsQ and ftsA are co-transcribed by a strong promoter, P(QA), present within the end of the ddl gene upstream of ftsQ. Transcription of P(QA) is turned on at the end of the DNA replication period, coincident with the end of the ftsZ transcription period. ftsA is also transcribed by another promoter, P(A), present between ftsQ and ftsA. P(A) transcription is approximately 10 times weaker than P(QA) and occurs during the DNA replication period. Transcription of ftsA by P(A) is sufficient for cell viability, but is not sufficient for normal cell division. When the transcription of ftsA is increased constitutively, cell division is inhibited and stalks are synthesized at aberrant positions. Thus, transcription of ftsA and ftsZ mimics their order of action in Caulobacter and proper transcription of ftsA has to be maintained for normal cell division and differentiation.

Photoresponses of the purple nonsulfur bacteria Rhodospirillum centenum and Rhodobacter sphaeroides.

We have measured the photoresponse of two purple nonsulfur bacteria, Rhodobacter sphaeroides and Rhodospirillum centenum, under defined conditions in a light beam propagating at 90 degrees to the optical axis of the microscope. This beam presented cells with a steep gradient of intensity perpendicular to the direction of propagation and a shallow gradient in the direction of light propagation. R. centenum, a species that reverses to change direction, accumulated in the light beam, as expected for a "scotophobic" response, while R. sphaeroides, which stops rather than reverses, accumulated outside the light beam. We also compared the behavior of liquid-grown R. centenum, which swims by using a single polar flagellum, to that of surface-grown R. centenum, which swarms over agar by using many lateral flagella and has been shown to move as colonies toward specific wavelengths of light. When suspended in liquid medium, both liquid- and surface-grown R. centenum showed similar responses to the light gradient. In all cases, free-swimming cells responded to the steep gradient of intensity but not to the shallow gradient, indicating they cannot sense the direction of light propagation but only its intensity. In a control experiment, the known phototactic alga Chlamydamonas reinhardtii was shown to swim in the direction of light propagation.

Dominant C-terminal deletions of FtsZ that affect its ability to localize in Caulobacter and its interaction with FtsA.

The cell division protein FtsZ is composed of three regions based on sequence similarity: a highly conserved N-terminal region of approximately 320 amino acids; a variable spacer region; and a conserved C-terminal region of eight amino acids. We show that FtsZ mutants missing different C-terminal fragments have dominant lethal effects because they block cell division in Caulobacter crescentus by two different mechanisms. Removal of the C-terminal conserved region, the linker, and 40 amino acids from the end of the N-terminal conserved region (FtsZdeltaC281) prevents the localization or the polymerization of FtsZ. Because two-hybrid analysis indicates that FtsZdeltaC281 does not interact with FtsZ, we hypothesize that FtsZdeltaC281 blocks cell division by competing with a factor required for FtsZ localization or that it titrates a factor required for the stability of the FtsZ ring. The removal of 24 amino acids from the C-terminus of FtsZ (FtsZdeltaC485) causes a punctate pattern of FtsZ localization and affects its interaction with FtsA. This suggests that the conserved C-terminal region of FtsZ is required for proper polymerization of FtsZ in Caulobacter and for its interaction with FtsA.

Cell cycle-dependent transcriptional and proteolytic regulation of FtsZ in Caulobacter.

In the differentiating bacterium Caulobacter crescentus, the cell division initiation protein FtsZ is present in only one of the two cell types. Stalked cells initiate a new round of DNA replication immediately after cell division and contain FtsZ, whereas the progeny swarmer cells are unable to initiate DNA replication and do not contain FtsZ. We show that FtsZ expression is controlled by cell cycle-dependent transcription and proteolysis. Transcription of ftsZ is repressed in swarmer cells and is activated concurrently with the initiation of DNA replication. At the end of the DNA replication period, transcription of ftsZ decreases substantially. We show that the global cell cycle regulator CtrA is involved in the cell cycle control of ftsZ transcription. CtrA binds to a site that overlaps the ftsZ transcription start site. Removal of the CtrA-binding site results in transcription of the ftsZ promoter in swarmer cells. Decreasing the cellular concentration of CtrA increases ftsZ transcription and conversely, increasing the concentration of CtrA decreases ftsZ transcription. Because CtrA is present in swarmer cells, is degraded at the same time as ftsZ transcription begins, and reappears when ftsZ transcription decreases at the end of the cell cycle, we propose that CtrA is a repressor of ftsZ transcription. We show that proteolysis is an important determinant of cell type-specific distribution and cell cycle variation of FtsZ. FtsZ is stable when it is synthesized and assembles into the cytokinetic ring at the beginning of the cell cycle. After the initiation of cell division, the rate of FtsZ degradation increases as both the constriction site and the FtsZ ring decrease in diameter. When ftsZ is expressed constitutively from inducible promoters, the abundance of FtsZ still varies during the cell cycle. The coupling of transcription and proteolysis to cell division ensures that FtsZ is inherited only by the progeny cell that will begin DNA replication immediately after cell division.

Effect of a covalently attached synergistic anion on chelator-mediated iron-release from ovotransferrin: additional evidence for two concurrent pathways.

The mechanism by which the iron-transport protein transferrin releases its iron in vivo is presently unclear. In vitro studies have implicated two concurrent chelator-mediated iron-release pathways: one which is hyperbolic in nature, involving a conformational change in the protein as a rate limiting step, and a second which has been proposed to be first-order in nature and to involve initial release of a synergistic anion. We have examined the effect that an affinity-label analog of the synergistic anion has on chelator-mediated iron-release from this protein. A covalently attached anion would inhibit iron-release via any pathway in which anion release is a prerequisite to iron release. The present investigation examined the effect that the covalently attached anion had on iron-release to pyrophosphate (PPi) and N, N-bis(phosphonomethyl)glycine (DPG), two chelators which are believed to utilize both pathways concurrently. Results show that when the affinity-label anion is utilized, strictly hyperbolic data are obtained, with similar observed kmax values. This is strong support for the hypothesis of a common, chelator-independent rate-limiting step for the one available pathway. These results also support strongly the hypothesis that synergistic anion removal is a prerequisite step to iron-release via the second pathway.