Low Frequency of Loss and Heterozygosity At the Nevoid Basal Cell Carcinoma Locus and Other Selected Loci in Appendageal Tumors

Previous studies of loss of heterozygosity (LOH) have revealed distinct patterns of allelic loss in some skin tumors. In basal cell carcinomas (BCCs) loss of heterozygosity is virtually restricted to chromosome 9, whereas in squamous cell carcinomas (SCCs) and actinic keratoses loss is more widespread involving chromosomes 3, 9, 13, and 17. Because there are histological similarities between BCCs and some appendageal tumors, and because some lines of evidence suggest that BCCs are appendageal in origin, we carried out a limited allelotype in 41 appendageal tumors. The overall frequency of allelic loss was low (4 out of 247 informative loci; 1.6%). LOH was seen in a proliferating trichilemmal cyst (l7p), a sebaceous epithelioma (l7q), an eccrine porocarcinoma (17q), a trichoepithelioma (9q), and in two basal cell carcinomas showing eccrine or granular cell differentiation that were originally misdiagnosed (9q). The pattern of loss in this mixed group of appendageal tumors shows differences from both BCCs and SCCs, and further emphasizes the unique genetic profile and behavior of BCCs. The finding of 9q loss in BCCs with eccrine or granular cell differentiation shows that 9q loss occurs in different histological subtypes of BCCs

Properties of Low-Lying Heavy-Light Mesons

We present preliminary results for the B meson decay constant and masses of low-lying heavy-light mesons in the static limit. Calculations were performed on the lattice in the quenched approximation using multistate smearing functions generated from a Hamiltonian for a spinless relativistic quark. The 2S--1S and 1P--1S mass splittings are measured. Using the 1P--1S charmonium splitting to set the overall scale, the ground state decay constant, f_B, is 319 +- 11 (stat) MeV.Comment: 8 pages, 9 figures, UCLA/92/TEP/4

Fully Complex Magnetoencephalography

Complex numbers appear naturally in biology whenever a system can be analyzed in the frequency domain, such as physiological data from magnetoencephalography (MEG). For example, the MEG steady state response to a modulated auditory stimulus generates a complex magnetic field for each MEG channel, equal to the Fourier transform at the stimulus modulation frequency. The complex nature of these data sets, often not taken advantage of, is fully exploited here with new methods. Whole-head, complex magnetic data can be used to estimate complex neural current sources, and standard methods of source estimation naturally generalize for complex sources. We show that a general complex neural vector source is described by its location, magnitude, and direction, but also by a phase and by an additional perpendicular component. We give natural interpretations of all the parameters for the complex equivalent-current dipole by linking them to the underlying neurophysiology. We demonstrate complex magnetic fields, and their equivalent fully complex current sources, with both simulations and experimental data.Comment: 23 pages, 1 table, 5 figures; to appear in Journal of Neuroscience Method

Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

BACKGROUND: Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported. RESULTS: This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip(®). Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1) Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-κB. (2) Interferon (IFN)-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-α/β receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN. CONCLUSION: This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-α/β receptor-mediated paracrine pathway

Extreme emotional disturbance: Legal frameworks and considerations for forensic evaluation

A significant minority of jurisdictions in the United States offer extreme emotional disturbance (EED) as a partial defense to murder. The form of this defense, as established by statute and case law, varies widely among jurisdictions. Empirical research on EED is scant with little guidance to forensic mental health professionals on how to approach and conceptualize potential EED cases. This paper addresses these issues by being the first known published work to (1) set forth a contemporary map of the varying definitions and scope of EED across the United States, (2) translate legal terminology into constructs accessible to forensic evaluators, and (3) provide legal and clinical analyses of sample EED cases to highlight key differences in the form of the defense and the admissibility of evidence between jurisdictions

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Aging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective

Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate

Aging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective