Tumor immunity to murine plasma cell tumors. III. Detection of common and unique tumor-associated antigens on BALB/c, C3H, and NZB plasmacytomas by in vivo and in vitro induction of tumor-immune responses.

Tumor-associated antigens (TAA) were demonstrated on plasmacytomas derived from BALB/c, NZB, and C3H mouse strains, by in vivo and in vitro techniques. By immunizing the appropriate F1 hybrid mice with these tumors, it was possible to show that all the plasmacytomas expressed cross-reactive tumor-associated transplantation antigens. When cytotoxic lymphocytes (CL) were induced in vitro by the coculturing of syngeneic or F1 hybrid spleen cells with irradiated plasmacytoma cells, "shared" and "unique" plasmacytoma TAA were demonstrable. This was accomplished by inducing CL in vitro against one syngeneic plasmacytoma and assaying for lytic activity on a range of 51Cr-labeled BALB/c, NZB and C3H plasmacytoma cells in vitro. In a second in vitro assay, unlabeled plasmacytoma cells were tested for their ability to inhibit the lysis of a particular 51Cr-labeled plasmacytoma, with the use of CL induced in vitro against it. The possibility that these TAA were "self" antigens was excluded by demonstrating in the inhibition assay that they were not present on T lymphomas and spleen cells of the same strain, and that CL "autosensitized" in vitro could not significantly lyse 51Cr-labeled plasmacytoma cells in vitro. From both in vivo and in vitro studies of immunity to these tumors, it was concluded that any one plasmacytoma line possesses multiple TAA of both shared and unique types.     

Treatment of selected neuromuscular patients with posterior instrumentation and arthrodesis ending with lumbar pedicle screw anchorage

STUDY DESIGN: This is a retrospective analysis of 23 patients with severe neuromuscular spinal deformity treated with posterior instrumentation and fusion ending in the lumbar spine. OBJECTIVES: The purposes of this study were to determine the safety and efficacy of stopping posterior instrumentation constructs in the lumbar spine with pedicle screw anchorage. SUMMARY OF BACKGROUND DATA: There are sparse data in the peer-reviewed literature regarding indications and outcomes in patients with neuromuscular disorders for instrumented fusion ended short of the pelvis with transpedicular fixation. METHODS: The average age of patients at surgery was 18.4 years (range, 10-61 years). Additional anterior discectomy and fusion were performed in four patients with large, stiff curves. No patient received anterior instrumentation. Criteria for exclusion of the pelvis from the fusion were less than 15 degrees of pelvic obliquity as a result of a compensatory curve below the major curve(s), the absence of problematic lower extremity contractures, and, often, the potential for ambulation. Process and clinical outcomes and complications were analyzed. RESULTS: Radiographic follow-up was available in 21 patients at an average of 62 months (range, 24-110 months) after surgery. Their average Cobb angle was 71 degrees before surgery, 25 degrees after surgery (64% correction), and 32 degrees at follow-up (54% correction). Their average spinal-pelvic obliquity was 6 degrees before surgery, 5 degrees after surgery, and 6 degrees at follow-up. The average lower instrumented vertebra was lumbar 3.7. Clinical follow-up was available for all 23 patients for an average of 61 months (range, 24-110 months). There were no perioperative deaths, deep wound infections, pseudarthroses, or instrument failures. Outcomes based on responses to questionnaires completed by patient, parent, or caregiver were highly satisfactory in 20 patients (87%), satisfactory in 2 patients (9%) and neither satisfactory nor unsatisfactory in 1 patient (4%). CONCLUSION: Posterior instrumentation and arthrodesis using lumbar lower instrumented vertebra pedicle screw anchorage can be performed safely and effectively, in selected patients patients with scoliosis and minimal pelvic obliquity.     

Soft tissue sarcomas of adults: state of the translational science.

Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality.     

Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy

Experimental laboratory data suggest that tumour growth is a balance between apoptosis and proliferation and that suppression of drug-induced apoptosis by oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in human breast tumours both prior to chemotherapy and in the residual resistant cell population at the completion of treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoperative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive association between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment. In the residual specimens AI and Ki67 were significantly reduced compared with pre-treatment biopsies, while Bcl-2 expression showed a significant increase. No differences were seen in the pre-treatment levels of any of the variables measured between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apoptosis and proliferation are closely related in vivo. It is possible that the phenotype of reduced apoptosis and proliferation, and increased Bcl-2 may be associated with breast cancer cells resistant to cytotoxic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response.     

Glutamatergic drugs exacerbate symptomatic behavior in a transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder

We previously created a transgenic mouse model of comorbid Tourette's syndrome and obsessive-compulsive disorder (TS+OCD), by expressing a neuropotentiating cholera toxin (CT) transgene in a subset of dopamine D1 receptor-expressing (D1+) neurons thought to induce cortical and amygdalar glutamate output. To test glutamate's role in the TS+OCD-like disorder of these transgenic mice (D1CT-7 line), the effects of glutamate receptor-binding drugs on their behavior were examined. MK-801, a non-competitive NMDA receptor antagonist that indirectly stimulates cortical-limbic glutamate output, aggravated a transgene-dependent abnormal behavior (repetitive climbing and leaping) in the D1CT-7 mice at doses insufficient to induce stereotypies, and more readily induced stereotypies and limbic seizure behaviors at high doses. NBQX, a seizure-inhibiting AMPA receptor antagonist, reduced only the MK-801-dependent stereotypic and limbic seizure behavior of D1CT-7 mice, but not their transgene-dependent behaviors. These data imply that TS+OCD-like behavior is mediated by cortical-limbic glutamate, but that AMPA glutamate receptors are not an essential part of this behavioral circuit. Our findings lead to the prediction that the symptoms of human Tourette's syndrome and obsessive-compulsive disorder are elicited by excessive forebrain glutamate output.     

Don’t Have No Time: Daily Rhythms and the Organization of Time for Low‐Income Families*

Using ethnographic data from Welfare, Children, and Families: A Three‐City Study, we examined time obligations and resource coordination of low‐income mothers. Longitudinal data from 75 African American, Hispanic, and non‐Hispanic White families residing in Chicago, including information on daily routines, perceptions of time, and access to resources, were gathered via participant observation and intensive semistructured interviews over 4 years. Results indicated that families constantly improvised daily rhythms to obtain and sustain resources, including child care, transportation, and social services. Participants were proactive in identifying and coordinating resources to transition from welfare to work or to maintain paid employment. Strategies used to coordinate resources and the cost associated with the inability to do so are discussed. Policy and social service recommendations are offered.