Suppression of immune response to sheep red blood cells in mice treated with preparations of a tumor cell component and in tumor-bearing mice

The frequency of rosette-forming cells (RFC) in spleens of mice immunized with sheep red blood cells (SRBC) was significantly reduced by pretreatment with preparations obtained from tumor extracts. This effect was not produced by preparations obtained by similar methods from normal tissue extracts. Significant suppression of RFC frequency was also found in spleens of mice immunized with SRBC at late stages of tumor growth, as compared to that in immunized controls and in mice bearing tumors at early stages. The results suggest that at late stages, a tumor cell component is released by tumor cells which may be similar to the nondialyzable immune suppressive factor(s) separated by us from tumor extracts, factors found in ascites fluid of tumor-bearing mice and those known to be released from tumor cells in vitro.     

Neurobehavioral Symptoms and Family Functioning in Traumatically Brain-Injured Adults

Traumatic brain injury (TBI) often results in a myriad of symptoms across physical, cognitive, and neurobehavioral domains. Despite inherent limitations associated with physical or cognitive impairments, the extant literature suggests that neurobehavioral symptoms tend to be the most distressing symptoms for the family and are more strongly related to poor outcome for the patient. The Neuropsychology Behavior and Affect Profile (NBAP) along with the General Functioning subscale of the Family Assessment Device (FAD-GF) and the Perceived Stress Scale were administered to 153 family members of persons who had sustained a TBI. The results provide new normative data and statistical support for the NBAP as a promising measure of neurobehavioral symptomatology following TBI. The correlation of.54 (p <.01) between FAD-GF and Full Scale NBAP scores provides powerful support for the hypothesis that family dysfunction is related to the presence of neurobehavioral symptoms in the patient. NBAP domains of Depression, Inappropriateness, Pragnosia, and Indifference appear most strongly related to family functioning and also bear a significant relationship to caregiver stress level and patient unemployment, whereas injury severity had little impact on either family functioning or neurobehavioral symptoms. The findings reinforce the significance of neurobehavioral symptoms and fortify their proposed link to family dysfunction post-TBI.     

Molecular determinants of human uveal melanoma invasion and metastasis

The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive, and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype, poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of multiple phenotypes – similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to predict the clinical outcome of patients with uveal melanoma. This revised version was published online in July 2006 with corrections to the Cover Date.     

The development of serum proteins and humoral immunity in opossum `embryos'

The development of serum proteins, immunoglobulins and the immune response was studied in opossum `embryos'. Serum proteins gradually increased from birth to 80 days of age when adult values were obtained. γM immunoglobulins were found at all stages of development but γG immunoglobulins were less regularly present. Those `embryos' which were 5 days or older at the time of immunization had an immune response to bacteriophage f2 and `embryos' 15 days or older responded to a hapten determinant, DNP. γM antibodies were most prominent but γG antibodies could also be detected in the immune response of opossum `embryos'.     

Optimal analysis of composite cytokine responses during alloreactivity

The one-way mixed lymphocyte reaction (MLR) is a useful model of the graft-vs.-host (GvH) response that occurs following bone-marrow transplantation (BMT). Previous studies of the MLR have shown high levels of type-1 cytokine production, such as IL-1, IL-6, IFN-γ and TNF-, but low or undetectable levels of type-2 cytokines, such as IL-4 and IL-10. Here, through establishing optimal conditions for the examination of levels and kinetics of a more definitive panel of type-1/type-2 cytokines (IL-4, IL-5, IL-10 and IL-13, IFN-γ, TNF- and the soluble IL-4 receptor) we show that, contrary to previously published data, the human alloresponse is truly heterogeneous, resulting in abundant type-2 as well as type-1 cytokine secretion. The kinetics of cytokine levels in the MLR show surprising complexity, suggesting a well-defined regulation as the alloresponse develops over time. Furthermore, each MLR responder:stimulator combination tested produces a composite cytokine profile that is intrinsic to that particular pairing. These combination-specific cytokine responses are reproducible when tested on multiple occasions over time. These data reveal a potential clinical application for the cytokine MLR in selecting donors for BMT with the least inflammatory cytokine profile. Additional analysis of this system reveals that the bulk of cytokine measured is both allospecific and T-cell-derived, with comparatively low levels produced through an autologous mechanism. Interestingly, although most of the cytokine detected is produced by CD45RO+ ‘mature/activated’ T cells, CD45RA+ ‘naive’ T cells are responsible for transient early production of IL-4. This novel finding suggests that naive T cells themselves could regulate type-1/type-2 developmental fate through an autocrine IL-4 mechanism.     

SKIN POTENTIAL, HEART RATE, AND THE SPAN OF IMMEDIATE MEMORY

Relations between orienting response and span of immediate memory were studied by measuring skin potential responses (SPR) and heart rate (HR). Four conditions were studied by presenting letters in a tachistoscope and a 1000 cycle, 100 db tone simultaneous on some but not all trials. The conditions (15 Ss in each) were: tone and letters for 10 trials, then letters alone for 10 trials; tone and letters for 20 trials; only letters for 10 trials, followed by letters and tone for 10 trials; and only letters for 20 trials. The results showed: (1) positive SPR habituated and negative did not, (2) tone produced more SP activity, (3) HR showed a shift from acceleration to deceleration over 20 trials, but tone had no influence, (4) tone had no direct influence on span scores, (5) Ss showed improvement in number ol letters reported correctly. There was a significant correlation between span and negative SPR when tone was sounded (r =. 36).