Ghassan Ghandour

Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile.

γδ T lymphocytes in the intestinal intraepithelial layer (γδ IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of γδ IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8+ αβ T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8+ αβ T cells must be activated to become cytotoxic effectors, γδ IELs are constitutively activated and appear to use different signaling cascades. Our data suggest that γδ IELs may respond efficiently to a broad range of pathological situations irrespective of their diverse T cell antigen receptor repertoire. γδ IELs may modulate local immune responses and participate in intestinal lipid metabolism, cholesterol homeostasis, and physiology. This study provides a strong basis for further investigations of the roles of these cells as well as mucosal immune defense in general.

Statistical Models for Behavioral Observations.

Statistical models for the Behavior Stream (renewal processes) are used to explore properties of behavioral observations. For continuous observation, statistical and psychometric properties are obtained for four types of behavioral measures: (i) empirical rates of behavior; (ii) empirical proportions, or relative frequencies, of a type of behavior; (iii) empirical prevalence (proportion of time the behavior occurs); and (iv) empirical event duration. Also, time-sampling alternatives to continuous observation are evaluated. Our formulation includes representations for three sources of unreliability: (a) finite observation time, (b) recorder errors, and (c) heterogeneity (instability) over occasions of observation. Traditional psychometric methods carried over from the analysis of responses to test items (including generalizability theory) are shown not to be applicable to behavioral observations. Our results provide a guide for design and a framework for statistical analysis in behavioral observation research.

Comparative statistics for DNA and protein sequences: multiple sequence analysis.

Concepts and methods [Karlin, S. & Ghandour, G. (1985) Proc. Natl. Acad. Sci. USA 82, 5800-5804] for the analysis of patterns and relationships are extended to multiple DNA and protein sequences. Functionals include multiple sequence common word occurrence distributions, characterizations of high frequency shared words, and ascertainment of long block identities. Various comparisons of sequences using natural alphabets obtained from grouping nucleotides or amino acids by their chemical and functional characteristics are described. Specific applications are given to globin genes, mitochondrial genomes, and a variety of mammalian viruses.

Algorithms for identifying local molecular sequence features.

Efficient algorithms are described for identifying local molecular sequence features including repeats, dyad symmetry pairings and aligned matches between sequences, while allowing for errors. Specific applications are given to the genomic sequences of the Epstein-Barr virus, Varicella-Zoster virus and the bacteriophages lambda and T7.

Cholesterol-related counseling by registered dietitians in northern California.

BACKGROUND An estimated 40 million Americans have serum cholesterol levels that warrant medically supervised dietary intervention. Although registered dietitians are expected to play an important role in treating these patients, current treatment practices in the community are largely unknown. METHODS A questionnaire concerning treatment practices was mailed to all 377 registered dietitians listed in the directories of the American Dietetic Association for two large California districts. Number of patients seen and length and content of dietary counseling were ascertained for three types of patients: (a) hypercholesterolemic outpatients without heart disease, (b) hypercholesterolemic outpatients who have heart disease, and (c) inpatients with myocardial infarction. RESULTS A return rate of 59% (n = 252) was obtained for the questionnaire. A total of 44% of the registered dietitians counseled hypercholesterolemic patients in any of the categories surveyed. About 30% of the respondents counseled hypercholesterolemic outpatients without heart disease. They saw an average of 4.9 such patients a week, spent an average of 53 min in an initial session, and usually did not see the patient again in follow-up. Fewer than 10% of patients had as many as four sessions. About 27% of the respondents saw hypercholesterolemic outpatients with heart disease, averaging 3.5 such contacts per week. The reported practices were similar to those provided to noncardiac outpatients. About 22% of registered dietitians worked with hospitalized myocardial infarction patients. They spent an average of a total of 41 min over 2.5 visits with each patient. CONCLUSION Currently, outpatient registered dietitian counseling for hypercholesterolemia appears to be limited in both the number of patients reached and the duration of the counseling. Further research into the impact of, barriers to, and efficacy of alternative delivery methods of dietary counseling is needed.

DNA sequence patterns in human, mouse, and rabbit immunoglobulin kappa-genes

SummaryDNA sequences of the human, mouse, and rabbit immunoglobulin kappa-gene (J-C regions) are compared with respect to various DNA patterns, including dyad symmetry pairings, runs of nucleotides, repeat clusters, and repeats that occur with unusually high frequency. The significant dyad symmetry pairings within each of the sequences emphasize the two “control-enhancer” elements of the J5-C intron. Dyad symmetry pairs between the J-C region and a number of kappa variable (V)-gene domains suggest differences in the affinities between the V and J segments. It is the “consensus heptamer” rather than the “consensus nonamer” that embodies the longest V-J dyad symmetry combinations. In the rabbit there are long runs and repeat clusters of the sequences that identify regions of high duplication; these regions are absent in the human and mouse sequences. High-frequency oligonucleotides feature the consensus nonamer 5′ to the J segments, especially in the mouse sequence.