Nephrotic syndrome. What is new since the 1988 study?

Hormone-refractory prostate cancer (HRPC) patients often have nonmeasurable disease. In such patients, predictive biomarkers other than tumor response may be required to compare therapeutic effects. We examined the predictive value for survival of various clinical and laboratory parameters, including prostate-specific antigen (PSA), in HRPC patients treated with suramin. Data from 103 HRPC patients were analyzed using various survival analyses, the likelihood ratio approach, and logistic regression analyses. When pretreatment factors, percentage decrease in PSA at 4 weeks from start of treatment (deltaPSA), and updated survival data were fit by a multivariate Cox proportional hazards model, acid phosphatase, lactate dehydrogenase, and deltaPSA were significant, with risk ratios close to 1. There was a decrease in likelihood ratio with increasing APSA. A logistic regression model was developed to predict the probability of <1 year of survival from the start of treatment. Hemoglobin and deltaPSA were found to be significant variables. However, in view of the complexities involving the relationship between PSA expression and prostate cancer growth and possible selective effect of treatment on PSA, further prospective testing is necessary. Therefore, deltaPSA cannot necessarily be used as a biomarker for survival response in individual patients during the evaluation of the therapeutic response of HRPC to new antineoplastic drugs.     

Calmodulin is essential for estrogen receptor interaction with its motif and activation of responsive promoter

Calmodulin (CaM) has been reported to have affinity for the estrogen receptor (ER). Observations reported here reveal a direct physical interaction between purified CaM and ER. This direct ER-CaM interaction may be an initial event preceding the assembly of ER plus auxiliary proteins into the active ER complex with its DNA motif, the estrogen response element. We demonstrate that CaM is an integral component of this complex by using a system reconstituted from purified ER and nuclear extract from ER-negative breast cancer cells and also with ER-depleted nuclear extract of an ER-positive breast cancer cell line. Although CaM is essential for formation of this complex, it is not sufficient, suggesting roles also of auxiliary proteins. CaM also is functionally required for activation of an ER-responsive promoter, in the 17beta-estradiol-ER pathway of hormone action and regulation of 17beta-estradiol-responsive gene expression that is associated with proliferation of mammary epithelial cells.     

Complex radiation diagnosis of retroperitoneal tumors and tumor-like states

The paper presents the results of complex radiation diagnosis of 118 cases of retroperitoneal tumors and tumor-like states, including 71 patients with tumors of mesenchymal origin, 7 with those of neurogenic origin, 6 with cysts, 9 with lymphogranulomatosis, 8 with retroperitoneal fibrosis, 12 with metastases, and 5 with hematomas. A wide complex of routine and up-to-date high-technology radiation diagnostic techniques was used to study the patients. The authors show the merits and dismerits of each technique. Greatest attention is given to the assessment of current techniques, primarily to ultrasonography (US) and computed tomography (CT). The studies have indicated that despite some specific features, many retroperitoneal tumors and tumor-like states bear similarities when various radiation methods are employed. The authors describe some syndromes which can be used to make a diagnosis. Despite the high capacities of US and CT in studying the normal and pathological structures of the human body, there are still great difficulties in differentiating different abnormalities when even the latest techniques are applied, these cases need paracentic aspiration or open biopsy.     

Calretinin-immunoreactive neurons in the human thalamus

To identify plant defense components that are important in restricting the growth of virulent pathogens, we screened for Arabidopsis mutants in the accession Columbia (carrying the transgene BGL2-GUS) that display enhanced disease susceptibility to the virulent bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326. Among six (out of a total of 11 isolated) enhanced disease susceptibility (eds) mutants that were studied in detail, we identified one allele of the previously described npr1/nim1/sai1 mutation, which is affected in mounting a systemic acquired resistance response, one allele of the previously identified EDS5 gene, and four EDS genes that have not been previously described. The six eds mutants studied in detail (npr1-4, eds5-2, eds10-1, eds11-1, eds12-1, and eds13-1) displayed different patterns of enhanced susceptibility to a variety of phytopathogenic bacteria and to the obligate biotrophic fungal pathogen Erysiphe orontii, suggesting that particular EDS genes have pathogen-specific roles in conferring resistance. All six eds mutants retained the ability to mount a hypersensitive response and to restrict the growth of the avirulent strain Psm ES4326/avrRpt2. With the exception of npr1-4, the mutants were able to initiate a systemic acquired resistance (SAR) response, although enhanced growth of Psm ES4326 was still detectable in leaves of SAR-induced plants. The data presented here indicate that eds genes define a variety of components involved in limiting pathogen growth, that many additional EDS genes remain to be discovered, and that direct screens for mutants with altered susceptibility to pathogens are helpful in the dissection of complex pathogen response pathways in plants.     

Congenital bilateral perisylvian syndrome

The congenital bilateral perisylvian syndrome is characterized by pseudobulbar palsy, moderate delay in mental and motor development and epilepsy. Three characteristic case stories are presented. Epileptic seizures are most frequently generalized: tonic, astatic, atypical absences and tonic-clonic seizures. Partial seizures are less frequent. Seizure control is often unsatisfactory. Neuroimaging demonstrates thickening of the cerebral cortex in the perisylvian area bilaterally; these changes together with the clinical picture establish the diagnosis. The etiology is unknown.     

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients

Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.     

The State of the Art of Spatial Interfaces for 3D Visualization

We survey the state of the art of spatial interfaces for 3D visualization. Interaction techniques are crucial to data visualization processes and the visualization research community has been calling for more research on interaction for years. Yet, research papers focusing on interaction techniques, in particular for 3D visualization purposes, are not always published in visualization venues, sometimes making it challenging to synthesize the latest interaction and visualization results. We therefore introduce a taxonomy of interaction technique for 3D visualization. The taxonomy is organized along two axes: the primary source of input on the one hand and the visualization task they support on the other hand. Surveying the state of the art allows us to highlight specific challenges and missed opportunities for research in 3D visualization. In particular, we call for additional research in: (1) controlling 3D visualization widgets to help scientists better understand their data, (2) 3D interaction techniques for dissemination, which are under‐explored yet show great promise for helping museum and science centers in their mission to share recent knowledge, and (3) developing new measures that move beyond traditional time and errors metrics for evaluating visualizations that include spatial interaction.     

Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14⁺⁺CD16⁺ monocytes, CD56⁺ CD16^dim natural killer cells, marginal zone-like IgD⁺CD27⁺ B cells, and on CD4⁺ and CD8⁺ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.