Polyamine biosynthesis is required for survival of sympathetic neurons after axonal injury

Treatment of adult rats with specific inhibitors of polyamine synthesizing enzymes prevented the early increase in ornithine decar☐ylase activity and polyamine content in the superior cervical ganglion after the postganglionic nerve was cut. Moreover, after axotomy, this treatment led to a marked diminution of the chromatolytic response with a marked neuronal cell death. We conclude that after axonal injury an early increase in polyamine biosynthesis, probably within parent sympathetic neurons, is an obligatory step in the progression of the axon reaction.     

Quality of Evidence to Compare Outcomes of Open and Robot-Assisted Laparoscopic Prostatectomy

Robot-assisted laparoscopic radical prostatectomy (RALP) has gained widespread acceptance in the treatment of prostate cancer. While it increasingly is becoming the surgical approach of choice in many centers, limited data exist directly comparing it to radical retropubic prostatectomy (RRP). This review examines the evidence comparing RALP to RRP. The outcomes evaluated are arranged into perioperative, oncologic, and functional outcomes. Of the 21 publications meeting our selection criteria, Level II, III, and IV evidence were found in 9, 1, and 11 articles, respectively. Overall, RALP was associated with lower blood loss, transfusion rates, length of stay, and higher cost when compared to RRP. Definitive conclusions regarding complications and oncologic and functional outcomes are not yet possible, and will require longer-term follow-up and well-designed randomized controlled trials.     

Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses

Rare sequence variants may be important in understanding the biology of common diseases, but clearly establishing their association with disease is often difficult. Association studies of such variants are becoming increasingly common as large-scale sequence analysis of candidate genes has become feasible. A recent report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS). The statistical evidence for this suggestion came from association analyses of a rare 3'-UTR variant, var321, which was observed in two patients but not observed in more than 2000 controls. We genotyped 307 Costa Rican and 515 Ashkenazi individuals (TS probands and their parents) and observed var321 in five independent Ashkenazi parents, two of whom did not transmit this variant to their affected child. Furthermore, we identified var321 in one subject from an Ashkenazi control sample. Our findings do not support the previously reported association and suggest that var321 is overrepresented among Ashkenazi Jews compared with other populations of European origin. The results further suggest that overrepresentation of rare variants in a specific ethnic group may complicate the interpretation of association analyses of such variants, highlighting the particular importance of precisely matching case and control populations for association analyses of rare variants.     

Quantitative flow cytometry of ZAP-70 levels in chronic lymphocytic leukemia using molecules of equivalent soluble fluorochrome

BACKGROUND: ZAP-70 has emerged as a potential pivotal prognostic marker for patients with chronic lymphocytic leukemia (CLL), which could replace immunoglobulin heavy chain mutation status. Although several flow cytometry assays have been described for assessing ZAP-70 in CLL, certain technical and scientific issues remain unsolved, which have prevented results of this crucial test from being reported, even in the best routine flow cytometry laboratories. In this report, we aimed to solve some of these issues by providing a computerized quantitative flow cytometric assay for ZAP-70 within the entire CLL population, which would be easy to perform and enable standardization between laboratories. METHODS: Intracellular ZAP-70 levels in CLL and normal B cells were assessed by molecules of equivalent soluble fluorochrome (MESF), employing Quantum FITC MESF calibration beads to establish a standard curve relating channel value to fluorescence intensity in MESF units and the QuickCal v. 2.2 program (www.bangslabs.com) and clinical relevance of the data was determined. RESULTS: The average ZAP-70 expression value in the CD19(+)/CD5(+) cells from 35 CLL patients was 103,701 MESF when compared with 12,621 MESF in B cells from 20 normal blood samples. "Low" and "high" ZAP-70 CLL subgroups were defined. Patients with "high ZAP-70 MESF" CLL had a shorter time to disease progression (P = 0.0005) and a more advanced clinical stage (P = 0.0018) when compared with patients in the "low ZAP-70 MESF" CLL subgroup. CONCLUSIONS: This quantitative analysis method can be employed to obtain a more specific and highly accurate assessment of ZAP-70 levels in CLL cells. The method can easily be standardized, in any routine flow laboratory, thereby improving reproducibility and reliability of ZAP-70 analysis.     

Beyond the patient: couple and family therapy for individual problems

We introduce the Journal of Clinical Psychology: In Session issue on couple and family therapies for adult psychological problems and health-compromising behaviors. The 8 articles, each with an extensive case study, represent different theoretical orientations (cognitive-behavioral, psychoeducational, systemic-strategic, experiential) and address problems with depression, anxiety, severe mental illness, substance use disorders, and dysfunctional coping with chronic illness. We identify points of consensus and divergence among the different therapies and consider implications for training psychotherapists.     

Family consultation for psychiatrically complicated health problems

We describe a social cybernetic view of health behavior problems and a team-based family consultation (FAMCON) format for strategic intervention based on that view. This approach takes relationships rather than individuals as the primary unit of analysis and attaches more importance to problem maintenance than to etiology. Treatment aims to interrupt two types of interpersonal problem maintenance-ironic processes and symptom-system fit (conceptualized, respectively, as positive and negative feedback cycles)-and to mobilize communal coping as a relational resource for change. A case example features a depressed husband and bipolar wife complaining of severe communication difficulties related to the husband's kidney cancer and diabetes. Over 6 consultation sessions, strategic interventions focused on interrupting ironic interpersonal patterns resolved the presenting complaint. Although cost-effectiveness is an open question, FAMCON may offer a useful alternative to psychoeducational and cognitive-behavioral treatments in the framework of stepped care.     

Monoclonal antibody to a DNA-binding domain of p53 mimics charge structure of DNA: anti-idiotypes to the anti-p53 antibody are anti-DNA

Antibodies to DNA are important markers of various autoimmune diseases and can be pathogenic; however, their generation is not understood. We previously reported that anti-DNA antibodies could be induced in mice by idiotypic immunization to PAb-421, an antibody to a DNA-binding domain of p53. We now report that two monoclonal antibodies of moderate affinity (K(D) asymptotically equal to 10(-7)), raised from PAb-421-immunized mice, specifically recognized both PAb-421 and DNA. These antibodies feature multiple arginine residues in the antigen-binding site, a unique characteristic of disease-associated anti-DNA antibodies; nevertheless, these anti-DNA antibodies show specific complementarity to PAb-421 by competing with p53 for PAb-421 binding and recognize defined oligonucleotides with a specificity similar to that of p53. To study the structural basis for the cross-recognition of PAb-421 and DNA by the anti-DNA antibodies, we constructed computer models (fine-tuned by protein-protein docking) of PAb-421 and one of the monoclonal anti-DNA antibodies. The modeled structures manifested structural complementarity. Most notably, the modeled structure of PAb-421 resembled the structure of DNA by the positions of negatively charged groups and aromatic side chains. Thus, a protein molecule may mimic the structure of DNA and the elusive generation of anti-DNA antibodies could be explained by idiotypic immunity to a DNA-binding protein, like p53.     

Molecular alterations in the TP53 gene of peripheral blood cells of patients with chronic myeloid leukemia

The TP53 gene has been extensively studied in patients with chronic myeloid leukemia (CML), both in chronic phase and in blast crisis. Mutations in the gene were found in up to 30% of the patients, especially among those in blast crisis. We report the results of an analysis of 29 blood samples from CML patients: 8 samples from chronic phase patients, 8 from patients in the accelerated phase, and 13 from patients in blast crisis. By using genomic DNA, we sequenced PCR products of the coding exons and most introns of the TP53 gene, finding genetic changes in 30% of the blast crisis samples and 12% in chronic phase. All mutations were found in introns and were previously unreported. Immunocytochemical studies revealed accumulation of TP53 in blood cells of samples both from chronic phase and blast crisis patients. Since these samples had no TP53 mutations, we believe that wild type TP53 accumulates in blood cells of CML patients. Our results, therefore, indicate that molecular changes in coding regions of the TP53 gene are rare. The significance of the abundance of intronic changes should be investigated further. Accumulation of wild type TP53 in CML cells may indicate an additional mechanism involving this gene in the pathogenesis of this disease. Genes Chromosomes Cancer 21:2–7, 1998. © 1998 Wiley-Liss, Inc.