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PubMed1993

Healing and the invention of metaphor: the effectiveness of symbols revisited.

In this essay, I argue that a theory of meaning adequate to account for the effectiveness of symbolic healing and psychotherapy requires some variant of the three concepts of myth, metaphor and archetype. Myth stands for the overarching narrative structures of the self produced and lent authority by cultural tradition. Archetype stands not for performed ideas or images, but for the bodily-given in meaning. Metaphor occupies an intermediate realm, linking narrative and bodily-given experience through imaginative constructions and enactments that allow movement in sensory-affective quality space. This pluralistic perspective itself constitutes a middle-ground between constructivist and realist approaches to meaning that can integrate causal and interpretive models of symbolic healing.

Fantasy↗
PubMed2006

A protocol for high-throughput phenotyping, suitable for quantitative trait analysis in mice.

Whole-genome genetic association studies in outbred mouse populations represent a novel approach to identifying the molecular basis of naturally occurring genetic variants, the major source of quantitative variation between inbred strains of mice. Measuring multiple phenotypes in parallel on each mouse would make the approach cost effective, but protocols for phenotyping on a large enough scale have not been developed. In this article we describe the development and deployment of a protocol to collect measures on three models of human disease (anxiety, type II diabetes, and asthma) as well as measures of mouse blood biochemistry, immunology, and hematology. We report that the protocol delivers highly significant differences among the eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6 J, DBA/2 J, and LP/J), the progenitors of a genetically heterogeneous stock (HS) of mice. We report the successful collection of multiple phenotypes from 2000 outbred HS animals. The phenotypes measured in the protocol form the basis of a large-scale investigation into the genetic basis of complex traits in mice designed to examine interactions between genes and between genes and environment, as well as the main effects of genetic variants on phenotypes.

Animals↗
PubMed2004

Classification of papillomaviruses.

One hundred eighteen papillomavirus (PV) types have been completely described, and a yet higher number of presumed new types have been detected by preliminary data such as subgenomic amplicons. The classification of this diverse group of viruses, which include important human pathogens, has been debated for three decades. This article describes the higher-order PV taxonomy following the general criteria established by the International Committee on the Taxonomy of Viruses (ICTV), reviews the literature of the lower order taxa, lists all known "PV types", and interprets their phylogenetic relationship. PVs are a taxonomic family of their own, Papillomaviridae, unrelated to the polyomaviruses. Higher-order phylogenetic assemblages of PV types, such as the "genital human PVs", are considered a genus, the latter group, for example, the genus "Alpha-Papillomavirus". Lower-order assemblages of PV types within each genus are treated as species because they are phylogenetically closely related, but while they have distinct genomic sequences, they have identical or very similar biological or pathological properties. The taxonomic status of PV types, subtypes, and variants remains unchanged and is based on the traditional criteria that the sequence of their L1 genes should be at least 10%, 2-10%, and maximally 2% dissimilar from one another.

Papillomaviridae↗
PubMed2002

Utilisation behaviour consequent to bilateral SMA softening.

The case of patient CU, who presented with severe utilisation behaviour, eventually unaccompanied by psychometric signs of frontal involvement, is reported. He suffered from a bilateral stroke within the territory of the anterior cerebral artery. His arterial system was characterised by a unique variant, whereby the right anterior cerebral artery was missing and three trunks originated from the left anterior cerebral artery, each bifurcating into right and left branches. An occlusion of the middle trunk immediately before its partition gave rise to a symmetrical bilateral parasagittal lesion that damaged the supplementary motor areas (medial part of Brodmann's area 6), sparing the lateral regions including the premotor cortices, the corpus callosum and the gyri cinguli. The hypothesis is put forward that utilisation behaviour should be conceived as a double anarchic hand, and its interpretation should rest on the damaged balance between the premotor cortices, responsive to environmental triggers, and the supplementary motor areas, which modulate actions and inhibit them. The imbalance due to the lesion would result in the patients being left at the mercy of environmental stimuli, unable to inhibit inappropriate actions. This intra-frontal hypothesis accounts for the data presented and those from the literature better than the previously held fronto-parietal equipoise.

Brain Mapping↗
PubMed1978

Adult age differences in reflection-impulsivity.

Adult age differences in reflection-impulsivity were examined on a modified version of Kagan's adult Matching Familiar Figures Test (MFF). The sample consisted of 20 elderly adults (mean age = 70.6) and 20 young adults (mean age = 21.9), each of whom was administered the modified MFF by an adult examiner. On half of the 24 items, the original (i.e., the standard) was present among the four alternatives ("original present" condition), while on the other half, all the alternatives were variants of the standard ("original not present" condition). The elderly subjects were generally more impulsive (had shorter latencies and committed more errors) than were the young adults. The results, though, varied somewhat with the two stimulus conditions employed. An analysis of the mean scores of both age groups indicated that the elderly took less time to respond only in the "original present" condition. A higher number of errors was observed for the older group in both conditions, and both age groups had fewer errors in the "original present" condition. Possible interpretations of these findings, in terms of age group differences in search strategy, anxiety, and other aspects of decision style are offered, and implications for further research are provided.

Adolescent↗
PubMed1997

Angiomyoid and follicular dendritic cell proliferative lesions in Castleman's disease of hyaline-vascular type: a study of 10 cases.

Castleman's disease of hyaline-vascular type (HV CD) may rarely be associated with a confusing variety of stromal cell overgrowths and neoplasms. We report here on the pathologic and clinical findings of 10 such cases. In addition to the usual complex histoimmunophenotype of the stroma of HV CD and some unusual features that mimicked neoplasms, we observed focal proliferations of angiomyoid (five cases) and follicular dendritic cell type (five cases). The former were nonneoplastic growths featuring compact tangles of spindle cells, exhibiting immunoreactivity for smooth muscle actin and interpreted as vessel-related pericytes and myoid cells. The latter were neoplastic growths of oval to spindle cells intermixed with lymphocytes; the tumor cells grew in long, intersecting bundles, featured various degree of atypia, and expressed the markers of follicular dendritic cells (CD21, CD35, KiM4p). The two types were clinically distinct. Four of five patients with angiomyoid proliferations were young women, who presented with an abdominal mass and were cured by surgery; that is, they had a clinical profile similar to that of patients with the stroma-rich variant of HV CD. The follicular dendritic cell proliferations were in older patients of either gender presenting with masses at various sites, recapitulating the profile of follicular dendritic cell tumors arising independently from HV CD; in three patients with long-term follow-up, recurrences or metastases developed at various intervals from the initial diagnosis (1 1/6, 3 1/2, and 11 years), and one patient died as a result. This study confirms the potential for, and the variety of, stromal cell proliferations in HV CD. Because their biologic behavior differs, correct identification of these various proliferative lesions is clinically important.

Actins↗
PubMed2004

Genetic and haplotype diversity among wild-derived mouse inbred strains.

With the completion of the mouse genome sequence, it is possible to define the amount, type, and organization of the genetic variation in this species. Recent reports have provided an overview of the structure of genetic variation among classical laboratory mice. On the other hand, little is known about the structure of genetic variation among wild-derived strains with the exception of the presence of higher levels of diversity. We have estimated the sequence diversity due to substitutions and insertions/deletions among 20 inbred strains of Mus musculus, chosen to enable interpretation of the molecular variation within a clear evolutionary framework. Here, we show that the level of sequence diversity present among these strains is one to two orders of magnitude higher than the level of sequence diversity observed in the human population, and only a minor fraction of the sequence differences observed is found among classical laboratory strains. Our analyses also demonstrate that deletions are significantly more frequent than insertions. We estimate that 50% of the total variation identified in M. musculus may be recovered in intrasubspecific crosses. Alleles at variants positions can be classified into 164 strain distribution patterns, a number exceeding those reported and predicted in panels of classical inbred strains. The number of strains, the analysis of multiple loci scattered across the genome, and the mosaic nature of the genome in hybrid and classical strains contribute to the observed diversity of strain distribution patterns. However, phylogenetic analyses demonstrate that ancient polymorphisms that segregate across species and subspecies play a major role in the generation of strain distribution patterns.

Animals↗
PubMed2004

Sampling and aliasing consequences of quarter-detector offset use in helical CT.

In this paper, the sampling and aliasing consequences of employing a quarter-detector-offset (QDO) in helical computed tomography (CT) are analyzed. QDO is often used in conventional CT to reduce in-plane aliasing by eliminating data redundancies to improve radial sampling. In helical CT, these same redundancies are exploited to improve longitudinal sampling and so it might seem ill-advised to employ QDO. The relative merit of the two geometries for helical CT is studied by conducting a multidimensional sampling analysis of projection-space sampling as well as a Fourier crosstalk analysis of crosstalk among the object's Fourier basis components. Both a standard fanbeam helical CT geometry and a hypothetical parallel-beam CT geometry, which helps illuminate the more complicated fanbeam results, are analyzed. Using the sampling analysis, it was found that the use of QDO leads to very different spectral tiling than arise when not using QDO. However, due to the shape of the essential support of the projection data spectra that arises in practice, both configurations lead to very similar or identical amounts of spectral overlap. This perspective also predicts the spatially variant longitudinal aliasing that has been observed in helical CT. The crosstalk results were consistent with those of the multidimensional sampling analysis. Thus, from the standpoint of aliasing and crosstalk, no compelling difference is found between the two geometries.

Algorithms↗
PubMed1999

Techniques to alleviate the effects of view aliasing artifacts in computed tomography.

Due to practical limitations in data acquisition, 3-D computed tomography systems must attempt to provide rapid reconstructions of acceptable quality from a limited number of views. The use of convolution backprojection (CBP) for image reconstruction from an inadequate number of projections, results in view aliasing artifacts. In this paper we investigate different post-processing methods of alleviating the effects of view aliasing artifacts. Two distinct methods and their variants are considered. The first, termed the intermediate view reprojection (IVR) method, involves estimating a set of intermediate views by reprojection, followed by a reconstruction using the augmented set of views. The second, termed the error-correction (EC) method, incorporates a correction on the initial reconstruction based on the projection-domain error. Suitable modifications and variants of the above methods are indicated. Of the methods discussed, the IVR method is simple, tends to reduce the effects of artifacts with less susceptibility to secondary effects, and is applicable to region-of-interest reconstructions.

Algorithms↗
PubMed2002

Surveillance for influenza--United States, 1997-98, 1998-99, and 1999-00 seasons.

PROBLEM/CONDITION: In the United States, influenza epidemics occur nearly every winter and are responsible for substantial morbidity and mortality, including an average of approximately 114,000 hospitalizations and 20,000 deaths/year. REPORTING PERIOD: This report summarizes both actively and passively collected U.S. influenza surveillance data from October 1997 through September 2000. DESCRIPTION OF SYSTEM: During each October-May in the period covered, CDC received weekly reports from 1) approximately 120 World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories in the United States regarding influenza virus isolations; 2) approximately 230, 375, and 430 sentinel physicians during 1997-98, 1998-99, and 1999-00, respectively, regarding their total number of patient visits and the number of visits for influenza-like illness (ILI); and 3) state and territorial epidemiologists regarding estimates of local influenza activity. WHO collaborating laboratories also submitted influenza isolates to CDC for antigenic analysis. Throughout the year, the vital statistics offices in 122 cities reported weekly on deaths related to pneumonia and influenza (P&I). RESULTS: During the 1997-98 influenza season, influenza A(H3N2) was the most frequently isolated influenza virus type/subtype. Influenza A(H1N1) and B viruses were reported infrequently. The proportion of respiratory specimens testing positive for influenza peaked at 28% in late January. The longest period of sustained excess mortality (when the percentage of deaths attributed to P&I exceeded the epidemic threshold) was 10 consecutive weeks. P&I mortality peaked at 9.8% in January. Visits for ILI to sentinel physicians exceeded baseline levels for 7 weeks and peaked at 5% in mid-January through early February. A total of 45 state epidemiologists reported regional or widespread activity at the peak of the season. During the 1998-99 season, influenza A(H3N2) viruses predominated; however, influenza B viruses were also identified throughout the United States. Influenza A(H1N1) viruses were identified rarely. The proportion of respiratory specimens testing positive for influenza peaked at 28% in early February. P&I mortality exceeded the epidemic threshold for 12 consecutive weeks and peaked at 9.7% in early March. Visits for ILI to sentinel physicians exceeded baseline levels for 7 weeks and peaked at 5% in early through mid-February. Forty-three state epidemiologists reported regional or widespread activity at the peak of the season. During the 1999-00 season, influenza A(H3N2) viruses predominated, but influenza A(H1N1) and B viruses also were identified. The proportion of respiratory specimens testing positive for influenza peaked at 31% in mid- to late December. The proportion of deaths attributed to P&I exceeded the epidemic threshold for 13 consecutive weeks and peaked at 11.2% in mid-January. Visits to sentinel physicians for ILI exceeded baseline levels 4 consecutive weeks and peaked at 6% in late December. Forty-four state epidemiologists reported regional or widespread activity at the peak of the season. INTERPRETATION: Influenza A(H1N1), A(H3N2), and B viruses circulated during 1997-2000, but influenza A(H3N2) was the most frequently reported virus type/subtype during all three seasons. Influenza A(H3N2) is the virus type/subtype most frequently associated with excess P&I mortality. Influenza activity during all three seasons occurred at moderate to severe levels, and excess P&I mortality was reported during > or = 10 weeks each year. PUBLIC HEALTH ACTIONS: CDC conducts active national surveillance during each October-May to detect the emergence and spread of influenza virus variants and to monitor influenza-related morbidity and mortality. Surveillance data are provided weekly throughout the influenza season to public health officials, WHO, and health-care providers and are used to guide vaccine strain selection, prevention and control activities, and patient care. Influenza vaccination is the most effective means for reducing the yearly effect of influenza. Typically, one or two of the influenza vaccine component viruses are updated each year so that vaccine strains will closely match circulating viruses. Surveillance data will continue to be used to select vaccine strains and to monitor the match between vaccine strains and the currently circulating viruses.

Disease Outbreaks↗
PubMedDate not supplied

Age-variant and age-invariant rhythmicities in the cortical and hippocampal electrical activities of neonatal rats.

The neocortical and hippocampal electrical activities were studied in 8, 15, 22, and 29-day-old rats. Segments of EEG recorded for 4 hours were analyzed by means of fast Fourier transformation. The sleep-wake activity stages were determined. The developments in the neocortical and hippocampal EEG activities were characterized by the gradual appearance of adult-like EEG waves and a shift towards higher frequencies in the theta wave range of the hippocampal electrical activity. The power value in the theta range, however, exhibited age-invariant rhythmicities with cycle lengths of about 9.5-11 and 16-22 min. The manifestation of such an age-invariant rhythm can be interpreted as an electrical manifestation of the rest-activity cycle originally described by KLEITMAN25.

Activity Cycles↗
PubMed1999

Unified approach to the analysis of genetic variation in serotonergic pathways.

Serotonin is a key neurotransmitter in the central nervous system, and dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex psychiatric diseases. Polymorphisms of many of the genes involved in serotonin biosynthesis, catabolism, and response have been reported, suggesting that genetic variability may underlie the development of diseases such as schizophrenia, obsessive compulsive disorder, and suicide. A number of single-gene polymorphisms in serotonergic pathways have been examined in these and other diseases, but to date results from this candidate gene approach have been disappointing. Although this may be because the detection of a small effect may require the analysis of large numbers of patients and controls, an alternative explanation is that the clinical importance of a single subtle genetic variant may be overlooked unless other functionally related genes are studied in tandem. To facilitate an integrated analysis, we have developed a PCR-SSP-based assay that permits the simultaneous genotyping of 13 single nucleotide polymorphisms in 9 serotonergic genes under identical conditions. These genes include tryptophan hydroxylase, tryptophan dioxygenase, monoamine oxidase A, and the serotonin receptors 5HT1A, 5HT1D-alpha, 5HT1D-beta, 5HT2A, 5HT2C, and 5HT5A. Using this technology, we have genotyped 100 Caucasoid control individuals and demonstrate that this approach is reliable, quick, cheap, and easy to interpret. We anticipate that this will facilitate the analysis of the genetic basis of susceptibility and phenotypic variability of a number of complex psychiatric diseases. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:621-627, 1999.

Codon↗
PubMed1999

Atypical plasmacytoid monomorphic adenoma of salivary glands of the tongue: cytologic, histologic, immunohistochemical, and ultrastructural findings.

We describe the case of an 11-yr-old boy with a 2.5-cm-diameter soft tumor superficially located at the dorsal aspect of the tongue. Fine-needle aspiration cytology smears showed plump epithelioid cells with round to mildly oval nuclei and open chromatin. One or two nucleoli of intermediate size were noticed in each nucleus. These cells appeared singly or in small groups. The findings were interpreted as containing plasmacytoid cells coming from an adenoma of salivary gland origin. The histologic examination of the surgical specimen revealed noncohesive, pleomorphic polygonal cells combining plasmacytoid/rhabdoid cytoplasmic features, with mild to moderate nuclear pleomorphism. One mitotic figure was observed per 10 high-power fields. Immunoreactivity was strongly positive for vimentin and S-100 protein, less intense for the cytokeratins, and negative for smooth muscle actin, muscle-specific actin, myoglobin, and GFAP. No ultrastructural evidences of myogenous differentiation were found. We propose that this case represents an unusual atypical variant of plasmacytoid monomorphic adenoma.

Adenoma↗
PubMed1983

Hemifacial microsomia and variants: pedigree data.

Ear malformations occur per se or together with other congenital anomalies. Many syndromes with ear malformations have been described. We have studied propositi with hemifacial microsomia (HFM) or Goldenhar syndrome (GS), also called oculoauriculovertebral "dysplasia" (OAV). In addition to ear malformations some individuals may have a small and/or malformed mandible, epibulbar, or conjunctival lipodermoids and anomalies of the cervical spine. Other malformations may also be seen. At present, the cause of these disorders is unclear. Here we present pedigree data on 97 propositi, 44 of whom had a family history of the same or similar anomaly. First-degree relatives were most often affected (35/433, 8%). Of 176 sibs tabulated, 11 (6%) were considered affected. The pattern of occurrence in many families suggested multifactorial determination, although other interpretations are possible. The occurrence of differing anomalies within a family suggests that the disorders constitute a single entity. The most frequent anomaly was a mild ear malformation (preauricular node or tag). This suggests a broad phenotypic spectrum. These data are useful for purposes of genetic counseling.

Ear, External↗
PubMed2005

Automated splicing mutation analysis by information theory.

Information theory-based software tools have been useful in interpreting noncoding sequence variation within functional sequence elements such as splice sites. Individual information analysis detects activated cryptic splice sites and associated splicing regulatory sites and is capable of distinguishing null from partially functional alleles. We present a server (https://splice.cmh.edu) designed to analyze splicing mutations in binding sites in either human genes, genome-mapped mRNAs, user-defined sequences, or dbSNP entries. Standard HUGO-approved gene symbols and HGVS-approved systematic mutation nomenclature (or dbSNP format) are entered via a web portal. After verifying the accuracy of input variant(s), the surrounding interval is retrieved from the human genome or user-supplied reference sequence. The server then computes the information contents (Ri) of all potential constitutive and/or regulatory splice sites in both the reference and variant sequences. Changes in information content are color-coded, tabulated, and visualized as sequence walkers, which display the binding sites with the reference sequence. The software was validated by analyzing approximately 1,300 mutations from Human Mutation as well as eight mapped SNPs from dbSNP designated as splice site variants. All of the splicing mutations and variants affected splice site strength or activated cryptic splice sites. The server also detected several missense mutations that were unexpectedly predicted to have concomitant effects on splicing or appeared to activate cryptic splicing.

Automation↗
PubMed2006

Post-glacial recolonization of the Great Lakes region by the common gartersnake (Thamnophis sirtalis) inferred from mtDNA sequences.

Pleistocene events played an important role in the differentiation of North American vertebrate populations. Michigan, in particular, and the Great Lakes region, in general, were greatly influenced by the last glaciation. While several hypotheses regarding the recolonization of this region have been advanced, none have been strongly supported. We generated 148 complete ND2 mitochondrial DNA (mtDNA) sequences from common gartersnake (Thamnophis sirtalis) populations throughout the Great Lakes region to evaluate phylogeographic patterns and population structure and to determine whether the distribution of haplotypic variants is related to the post-Pleistocene retreat of the Wisconsinan glacier. The common gartersnake was utilized, as it is believed to have been one of the primary vertebrate invaders of the Great Lakes region following the most recent period of glacial retreat and because it has been a model species for a variety of evolutionary, ecological, behavioral, and physiological studies. Several genetically distinct evolutionary lineages were supported by both genealogical and molecular population genetic analyses, although to different degrees. The geographic distribution of the majority of these lineages is interpreted as reflecting post-glacial recolonization dynamics during the late Pleistocene. These findings generally support previous hypotheses of range expansion in this region.

Animals↗
PubMed2007

Interpretation of multiple probe sets mapping to the same gene in Affymetrix GeneChips.

BACKGROUND: Affymetrix GeneChip technology enables the parallel observations of tens of thousands of genes. It is important that the probe set annotations are reliable so that biological inferences can be made about genes which undergo differential expression. Probe sets representing the same gene might be expected to show similar fold changes/z-scores, however this is in fact not the case. RESULTS: We have made a case study of the mouse Surf4, chosen because it is a gene that was reported to be represented by the same eight probe sets on the MOE430A array by both Affymetrix and Bioconductor in early 2004. Only five of the probe sets actually detect Surf4 transcripts. Two of the probe sets detect splice variants of Surf2. We have also studied the expression changes of the eight probe sets in a public-domain microarray experiment. The transcripts for Surf4 are correlated in time, and similarly the transcripts for Surf2 are also correlated in time. However, the transcripts for Surf4 and Surf2 are not correlated. This proof of principle shows that observations of expression can be used to confirm, or otherwise, annotation discrepancies. We have also investigated groups of probe sets on the RAE230A array that are assigned to the same LocusID, but which show large variances in differential expression in any one of three different experiments on rat. The probe set groups with high variances are found to represent cases of alternative splicing, use of alternative poly(A) signals, or incorrect annotations. CONCLUSION: Our results indicate that some probe sets should not be considered as unique measures of transcription, because the individual probes map to more than one transcript dependent upon the biological condition. Our results highlight the need for care when assessing whether groups of probe sets all measure the same transcript.

Animals↗
PubMedDate not supplied

Effect of apolipoprotein E variants on plasma lipids and apolipoproteins in the Orang Asli ('aborigines') of Malaysia.

Members of the Semai group of Orang Asli ('aborigines') in peninsular Malaysia were examined for apolipoprotein E (apo E) variants in relation to plasma total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDLC), triglycerides (TG), apolipoprotein AI and apolipoprotein B (apo B). The e2 and e4 alleles were found to be higher than in most other groups as reported. The sample as a whole was normotriglyceridaemic (mean plasma TG, 1.5 mmol/l) and very markedly hypocholesterolaemic (mean plasma TC 1.7 mmol/l). The distribution of apo E variants was not related to any of the plasma lipids or apolipoprotein fractions using results from all subjects, but if a distinctly hypertriglyceridaemic sub-section was omitted (TG > 1.7 mmol/l) then apo E variants were determinants of plasma TC, LDLC, and apo B concentrations, the lower values of these being associated with the 2-2 and 2-3 genotypes, and the higher with 3-4, and 4-4.

Alleles↗

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