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Challenges to understanding spatial patterns of disease: philosophical alternatives to logical positivism.

Most studies of disease distribution, in medical geography and other related disciplines, have been empirical in nature and rooted in the assumptions of logical positivism. However, some of the more newly articulated philosophies of the social sciences, and of social theory, have much to add in the understanding of the processes and mechanisms underlying disease distribution. This paper represents a plea for creative synthesis between logical positivism and realism or structuration, and uses specific examples to suggest how disease distribution, as a surface phenomenon, can be explained using deeper analysis.

Cross-Cultural Comparison

Spatial patterns and travelling waves in population genetics.

We consider a reaction-diffusion equation to model a multi-allelic, single locus problem. The population can migrate in a homogeneous region and the diffusion rates depend upon the genotype. It is shown that if there is an equilibrium point with all alleles present and if this polymorphism is stable for the classical reaction system then it is also stable for the reaction-diffusion equation. Also a simplified model is used to investigate which allele will spread in the two-allele case. Alleles which are associated with large fitness and small dispersion do best.

Alleles

Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits.

Mildly thirsty rabbits were classically conditioned by reinforcement with water to give a discriminative licking response to the presentation of odors. The jaw movement component of the licking conditioned response (JM CR) was elicited only by the reinforced odor; an increase in the relative frequency of sniffing (RR CR) occurred to both reinforced (CS+) and nonreinforced (CS-) odors. Oscillatory electroencephalographic bursts of high-frequency (40-80 Hz) potentials were recorded epidurally from the lateral olfactory bulb with 64-electrode arrays (8 X 8, 3.5 X 3.5 mm) chronically implanted. Emphasis was on comparing bursts during odor presentation with bursts preceding odor arrival on each trial. A "detection" burst was characterized as occurring immediately after odor arrival and before the sniff response. "Discrimination" bursts occurred during the RR CR and before the JM CR onset. Significant air-odor burst differences (together with sniffing) occurred through up to six sessions for both CS+ and CS- odors for "discrimination" bursts but not for "detection" bursts.

Animals

Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis.

A regulatory cascade, initiated during the syncytial stage of embryogenesis, culminates in the striped pattern of engrailed gene expression at the cellular blastoderm stage. The early regulatory genes, for example the pair-rule genes, are expressed transiently and as their products decay a distinct regulatory programme involving segment polarity genes takes over. This late programme maintains and perhaps modifies the striped pattern of engrailed expression through interactions that may involve cell communication.

Animals

Spatial patterns in electoral wards with high lymphoma incidence in Yorkshire health region.

The possibilities of clustering between those electoral wards which display higher than expected incidences of cases of the lymphomas occurring between 1978 and 1982 are examined. Clusters are defined as being those wards with cases in excess (at a probability of less than 10%) which are geographically adjacent to each other. A separate analysis extends the definition of cluster to include high incidence wards that are adjacent or separated by one other ward. The results indicate that many high incidence lymphoma wards do occur close together and when computer simulations are used to compute expected results, many of the observed results are shown to be highly improbable both in the overall number of clustering wards and in the largest number of wards comprising a 'cluster'.

Computer Simulation

Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development.

The p34 protein kinase encoded by the cdc2 gene is a key component of the eukaryotic cell cycle required for the G1- to S-phase transition and entry into mitosis. To study the regulation of plant meristem activity and cell proliferation, we have examined the tissue-specific accumulation of cdc2 transcripts in Arabidopsis thaliana and the related crucifer radish (Raphanus sativus) by in situ hybridization using A. thaliana cdc2 cDNA sequences as a probe. cdc2 transcripts accumulated in leaf primordia and within the vegetative shoot apical meristem. During flower development, high levels of expression were observed in meristems, in the basal regions of developing organs, in the developing vasculature, and associated with rib meristems elaborated late in the development of some floral organs. In root tips, cdc2 transcripts accumulated in the meristematic region and adjacent daughter cells but were not detected in the quiescent center. There was strong hybridization throughout the pericycle, and a further localized accumulation of cdc2 transcripts was observed in the initial stages of the activation of a new meristem at sites of lateral root development. We conclude that cdc2 expression is a critical factor in the regulation of meristem activity and establishment of proliferative competence.

Base Sequence

Spatial pattern of receptor expression in the olfactory epithelium.

A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset of olfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system.

Amino Acid Sequence

Spatial pattern of myosin phosphorylation in contracting smooth muscle cells: evidence for contractile zones.

We have purified a polyclonal antibody by affinity chromatography which binds specifically to the phosphorylated form of the regulatory light chain (Mr = 20,000) of smooth muscle myosin. This antibody does not stain relaxed, permeabilized smooth muscle cells isolated from guinea pig taenia coli. However, when these cells were stimulated to contract with CaCl2 (100 microM) and ATP (1 mM), the immunofluorescence staining was localized in a series of transverse bands. This distribution of activated myosin appears to reflect an underlying structural organization of the smooth muscle cell cytoskeleton into mechanically coupled contractile zones.

Animals

Spatial patterns in the fruiting bodies of the cellular slime mold Polysphondylium pallidum.

During morphogenesis in the slime mold Polysphondylium pallidum cell masses are periodically pinched off from the base of the developing sorogen. These masses round up and differentiate into secondary sorogens, which become radially ordered arrays of secondary fruiting bodies called whorls. Here we describe the morphogenesis of P. pallidum and characterize the spacing of whorls along the central stalk of the fruiting body and the spacing of sorocarps within whorls. We find both are highly regular. We propose that the linear spacing of whorls can be accounted for satisfactorily by a model that views the periodic release of cell masses from the base of the developing sorogen as the consequence of an imbalance between forces that orient amoebae toward the tip of the culminating sorogen, and cohesive forces between randomly moving cells in the basal region of the sorogen, which act as a retarding force. The orderly arrangement of fruiting bodies within whorls can be explained most easily by models that employ short-range activation and lateral inhibition.

Cell Differentiation

[Spatial pattern and microvascularization of the ductuli efferentes testis of bulls (Bos taurus)].

The arrangement, origin, course and opening of the ductuli efferents testis of the bull (Bos taurus) were visualized using scanning electron microscopy. The corresponding capillary structure was also described and documented with the help of corrosive microanatomical casts. The number of the ductuli efferents testis of the bull varies narrowly between 12 to 13. Ductuli removed from the surrounding tissue have a length of up to 78 cm. The duct system is composed of linear as well as tortuous parts, permitting division into three distinct segments. Blind ending ductules are very short. We therefore do not see these structures as being associated with spermiostasis. The capillary density as well as the capillary architecture show regional peculiarities. All segments of the ductuli efferents testis are composed of capillaries of the continuous type. The findings indicate that the increased capillary density in the voluminous initial section of the ductuli efferents testis represents the basis for resorptive as well as secretory activities in the bull.

Animals

Developmental and spatial patterns of expression of the mouse homeobox gene, Hox 2.1.

The Hox 2.1 gene forms part of a cluster of homeobox-containing genes on mouse chromosome 11. Analysis of Hox 2.1 cDNAs isolated from an 8 1/2-day p.c. mouse embryo library predicts that the gene encodes a 269 amino acid protein (Mr, 29,432). This deduced protein contains a homeobox 15 amino acids from the carboxy terminus and is very rich in serine and proline. A second partially conserved region present in several other genes containing homeoboxes, the hexapeptide Ile-Phe-Pro-Trp-Met-Arg, is located 12 amino acids upstream of the homeodomain and is encoded by a separate exon. Analysis of Hox 2.1 gene expression reveals a complex and tissue-specific series of RNA transcripts in a broad range of fetal tissues (lung, spinal cord, kidney, gut, spleen, liver and visceral yolk sac). Comparison of the temporal patterns of gene expression during development and in the adult suggests that Hox 2.1 is regulated independently in different tissues. Evidence is also presented that transcripts from other loci have extensive homology to the Hox 2.1 gene in sequences outside of the homeobox. In situ hybridization shows that Hox 2.1 transcripts are regionally localized in the spinal cord in an apparent anterior-posterior gradient extending from the hind brain. The distribution of RNA also displays a cell-type specificity in the lung, where mesodermal cells surrounding the branching epithelial cell layer accumulate high levels of Hox 2.1 transcripts.

Amino Acid Sequence

Nucleoli and AgNOR proteins in 32 cases of primary breast carcinoma. Spatial pattern of interactions between 50 clinical and histometric criteria.

The purpose of this paper is to analyze a method allowing selection of the best morphometric criterion for quantifying AgNOR proteins under conventional observation conditions by light microscopy. We determined 50 parameters for 32 cases of primary breast carcinoma. For each case, three 100-nucleus samples (tumor center and periphery on a Giemsa-stained, 3-microns tumor section, periphery on a silver-stained section) were quantified. Distribution-free multidimensional data analysis was used to explore the geometric significance of the coefficient of correlation. This analysis revealed a clinical message linked with the largest "nucleolar structure" (nucleolus or AgNOR clump) per nucleus on the tumor periphery. Tumor recurrence or death correlated only with the coefficient of variation of the "nucleolar/nuclear" ratio of the greatest clump of AgNORs per nucleus periphery (CVRSa). The prognostic value of CVRSa is independent of that of conventional criteria, such as age, tumor size, Scarff-Bloom-Richardson grading and lymph node status. The largest AgNOR clump per nucleus may prove to be a further practical prognostic predictor.

Biometry