Mycosis fungoides: developments in incidence, treatment and survival.

BACKGROUND: Prior studies have demonstrated improved disease-specific survival of mycosis fungoides (MF) patients over the last 50 years. OBJECTIVE: To analyse patterns of survival and incidence from 1973 to 2016 and determine whether apparent improvements in MF-specific survival are due to lead-time bias rather than improvements in treatment. METHODS: We performed an analysis of 10 155 patients diagnosed with MF from 1973 to 2016 in the United States cancer registries of SEER-18. We also performed a literature review of papers including stage data for unselected populations of MF patients prior to 2000. RESULTS: Incidence of MF increased from 3.0 per million person-years in the 1970s to 5.9 in the 2010s. For all cohorts, non-Hodgkin lymphoma (including MF) was the leading cause of death. Survival analysis demonstrated marked improvement in disease-specific and overall survival from the 1970s to 2010s. Based on systematic review of the literature, 32%-73% of patients diagnosed prior to 2000 were diagnosed with early-stage disease, as opposed to 81% of patients in the SEER 2000-2016 cohort (P < 0.035 for all cohorts). CONCLUSIONS: Although there have been improvements in MF-related survival over the last 50 years, these may reflect improvements in our ability to diagnose early-stage disease rather than improved treatment.

VEEVVIE: Visual Explorer for Empirical Visualization, VR and Interaction Experiments.

Empirical, hypothesis-driven, experimentation is at the heart of the scientific discovery process and has become commonplace in human-factors related fields. To enable the integration of visual analytics in such experiments, we introduce VEEVVIE, the Visual Explorer for Empirical Visualization, VR and Interaction Experiments. VEEVVIE is comprised of a back-end ontology which can model several experimental designs encountered in these fields. This formalization allows VEEVVIE to capture experimental data in a query-able form and makes it accessible through a front-end interface. This front-end offers several multi-dimensional visualization widgets with built-in filtering and highlighting functionality. VEEVVIE is also expandable to support custom experimental measurements and data types through a plug-in visualization widget architecture. We demonstrate VEEVVIE through several case studies of visual analysis, performed on the design and data collected during an experiment on the scalability of high-resolution, immersive, tiled-display walls.

Marked increase in mitochondrial DNA deletion levels in the cerebral cortex of Huntington's disease patients.

To determine if somatic mtDNA mutations might contribute to the neurodegeneration observed in Huntington's disease (HD), we quantitated the amount of the common mitochondrial 4977 nucleotide pair deletion (mtDNA4977) in cortex and putamen of HD patients and age-matched controls by the serial dilution-polymerase chain reaction method. Cortical deletion levels were analyzed in the temporal, frontal, and occipital lobes. HD temporal lobes had an 11-fold greater mean mtDNA4977 deletion level than age-matched controls, and HD frontal lobes had fivefold greater levels. HD occipital lobe and putamen deletion levels were comparable with control levels. These results support the hypothesis that HD is associated with elevated cortical mtDNA damage.

Variable retinal and neurologic manifestations in patients harboring the mitochondrial DNA 8993 mutation.

OBJECTIVE: Ophthalmologic and neurologic manifestations of the mitochondrial DNA mutation at position 8993 (MTATP*NARP8993) are reported and compared with previously published reports of patients with the 8993 mutation and other mitochondrial disorders. DESIGN: Pedigree analysis. SETTING: University referral center. PATIENTS: Eight subjects from two unrelated pedigrees that were positive for the mitochondrial DNA replacement mutation at nucleotide position 8993 were evaluated ophthalmologically and neurologically. RESULTS: Retinal abnormalities ranged from mild salt-and-pepper changes to severe retinitis pigmentosa-like changes with maculopathy. Neurologic manifestations were also highly variable and ranged from migraine headaches to severe dementia and Leigh's disease. CONCLUSIONS: The type and extent of retinal pigmentary changes and neurologic findings varied substantially, even among members of the same family. These changes, although not specific for the MTATP*NARP8993 mutation, are highly suggestive of mitochondrial disease.

Physical studies on the membranes and lipids of plasmalogen-deficient Megasphaera elsdenii.

Membrane fluidity and thermotropic phase behavior in the wild-type and plasmalogen-deficient strains of Megasphaera elsdenii have been studied by means of diphenylhexatiene steady state fluorescence anisotropy in isolated membranes, and by 31P-NMR and X-ray diffraction of the isolated phospholipids. Compared to the wild-type plasmalogen content of greater than 75%, plasmalogen-deficient strains had less than 5% plasmalogen, consisting largely of phosphatidylethanolamine and phosphatidylserine. Steady state fluorescence anisotropy measurements yielded an order parameter which was 6% lower in the plasmalogen-deficient membranes from 10 degrees to 40 degrees C, indicating higher membrane lipid mobilities. Both 31P-NMR and X-ray diffraction revealed the formation of a hexagonal phase in the lipids from the wild-type strain starting above 30 degrees C. In general the transition was not complete by 80 degrees C. In contrast, phospholipids from plasmalogen-deficient strains appeared to form a relatively stable lamellar phase.

A novel approach to extract colon lumen from CT images for virtual colonoscopy.

An automatic method has been developed for segmentation of abdominal computed tomography (CT) images for virtual colonoscopy obtained after a bowel preparation of a low-residue diet with ingested contrast solutions to enhance the image intensities of residual colonic materials. Removal of the enhanced materials was performed electronically by a computer algorithm. The method is a multistage approach that employs a modified self-adaptive on-line vector quantization technique for a low-level image classification and utilizes a region-growing strategy for a high-level feature extraction. The low-level classification labels each voxel based on statistical analysis of its three-dimensional intensity vectors consisting of nearby voxels. The high-level processing extracts the labeled stool, fluid and air voxels within the colon, and eliminates bone and lung voxels which have similar image intensities as the enhanced materials and air, but are physically separated from the colon. This method was evaluated by volunteer studies based on both objective and subjective criteria. The validation demonstrated that the method has a high reproducibility and repeatability and a small error due to partial volume effect. As a result of this electronic colon cleansing, routine physical bowel cleansing prior to virtual colonoscopy may not be necessary.

A survey of architectures for volume rendering.

Five hardware architectures for volume rendering, which requires efficiently handling a huge amount of volumetric data, are surveyed, categorized, and compared. They are Cube, Insight, PARCUM, Voxel Processor, and 3DP. General-purpose graphics systems that exploit their surface-based geometry engine to reduce the computational burden of the rendering process are briefly reviewed.

Modified Dendrogram of Attribute Space for Multidimensional Transfer Function Design.

We introduce a modified dendrogram (MD) (with subtrees to represent clusters) and display it in 2D for multidimensional transfer function design. Such a transfer function for direct volume rendering employs a multidimensional space, termed attribute space. The MD reveals the hierarchical structure information of the attribute space. The user can design a transfer function in an intuitive and informative manner using the MD user interface in 2D instead of multidimensional space, where it is hard to ascertain the relationship of the space. In addition, we provide the capability to interactively modify the granularity of the MD. The coarse-grained MD primarily shows the global information of the attribute space while the fine-grained MD reveals the finer details, and the separation ability of the attribute space is completely preserved in the finest granularity. With this so called multigrained method, the user can efficiently create a transfer function using the coarse-grained MD, and then fine tune it with the fine-grained MDs. Our method is independent on the type of the attributes and supports arbitrary-dimension attribute space.

Disappearance of plasmalogen-containing phospholipids in Megasphaera elsdenii.

The plasmalogen content of phospholipids isolated from Megasphaera elsdenii ATCC 17752 decreased markedly in cultures passed serially at intervals of 3 to 6 weeks. From the wild-type ratio of vinyl ether to lipid phosphorus of 0.8, clones were isolated with ratios less than 0.05. Clonal analysis, as well as the reproducibility of the phenomenon and the long time course, suggest that the loss of plasmalogens is an adaptive process. Although small variations in cell morphology and ratios of end products of fermentation were detected, plasmalogen-rich and -deficient cells were virtually indistinguishable with respect to growth rates, range of fermentable carbohydrates, activities of selected enzymes, and electrophoretic patterns in both membrane and soluble proteins. Large decreases in saturated fatty acid production accompanied the decline of plasmalogens.

Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain.

A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age-related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/micrograms of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10-fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15-fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age-related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age-dependent increases in incidence of neurodegenerative diseases.

Novel mitochondrial DNA deletion found in a renal cell carcinoma.

Polymerase chain reaction (PCR) was used to analyze a rarely deleted region of mitochondrial DNA (mtDNA) from 39 human renal cell carcinomas (RCC) and matched normal kidney tissue removed during radical nephrectomy. One tumor specimen (E.R.) had a unique PCR product approximately 250 base pairs (bp) smaller than the PCR product found in the normal E.R. kidney. Sequence analysis of the tumor-specific PCR fragment revealed a 264 bp deletion in the first subunit (NDI) of NADH:ubiquinone oxidoreductase (complex I) of the electron transport chain. Southern analysis of the RCCs demonstrated that approximately 50% of the mtDNA molecules in the primary RCC contained a unique 3.2 kb EcoRV restriction fragment found only in E.R. tumor mtDNA. Northern analysis demonstrated preferential transcription of the truncated NDI mRNA. None of the five metastases or any normal tissue from E.R. contained levels of the NDI deletion detectable by PCR. This is the first reported case of an intragenic NDI mtDNA deletion.