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Enhanced immune priming with spatial distribution of paracrine cytokine vaccines.

In preclinical models, tumor cells genetically modified to express cytokines or other costimulatory molecules can generate systemic antitumor immunity. In some cases, these tumor vaccines have been shown to eradicate micrometastases. These results have led to the initiation of numerous phase I clinical trials employing either autologous or allogeneic tumor vaccines genetically modified to express cytokines and other genes. In this report, we use our murine model to identify a number of parameters that may be critical for enhancing vaccine efficacy. In addition to antigen dose and cytokine level, the distribution of vaccine inoculation was found to have a significant impact on vaccine potency. These results require consideration in early clinical trials designed to evaluate cellular vaccine therapy.

Animals↗

Spatial distribution of thoron and radon concentrations in the indoor air of a traditional Japanese wooden house.

A radon-thoron discriminative passive dosimeter has been developed that can estimate both radon (222Rn) and thoron (220Rn) concentrations at the same time. Two polycarbonate films are installed as solid-state nuclear track detectors in the dosimeter housing. One film registers alpha tracks originating from predominantly thoron and its progeny together with a small contribution from radon, and the other film registers alpha tracks originating from radon and its progeny together with a negligible contribution from thoron. The lower detection limit is estimated to be 2.9 Bq m-3 for the radon concentration and 9.0 Bq m-3 for the thoron concentration for 2 mo exposure. Preliminary measurements from 1991-1992, in a traditional Japanese wooden house located in Kyoto, indicated that the indoor thoron concentration increases exponentially as the interior mud (or plaster-coated) wall is approached. A soil-based plaster commonly used in Japanese wooden houses to fill walls (or as a surface coating on the walls) is the probable source of the indoor thoron. Since thoron is not measured by the usual radon measurements, and the majority of Japanese houses are made of wood, attention should be paid to indoor thoron and its decay products, which may give a significant fraction of the total natural radiation exposure to the general public.

Air Pollutants, Radioactive↗

An analysis of the spatial distribution of attenuation values in computed tomographic scans of liver and spleen.

An autocorrelation analysis of the attenuation values in computed tomographic scans has been performed for a total of 35 normal and eighteen cirrhotic patients. The results confirm preliminary observations on a smaller sample which suggested that this technique may be used to separate normal and cirrhotic livers. The noise structure in a region within the spleen was also examined and found to change in the presence of cirrhosis.

Humans↗

Spatial distribution of tumor vaccine improves efficacy.

OBJECTIVES: Genetically engineered tumor cells were used as a vaccine in a murine model to compare tumor formation after inoculating multiple sites versus a single site. The effect of vaccinating draining lymph node basins was evaluated. STUDY DESIGN: Mice were vaccinated in either the floor of the mouth, the draining nodes of the front legs, the hind leg, or a combination of sites. Seven days later, the mice were challenged with parental tumor cells in the floor of the mouth and followed for tumor growth. METHODS: A retroviral vector was used to transduce the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene into SCCFVII/SF tumor cells, which were then irradiated to prevent replication in vivo. Syngeneic C3H/HeJ mice were vaccinated with 1 x 10(6) cells in various sites, then challenged with 1 x 10(5) parental cells after 7 days. RESULTS: Animals vaccinated in multiple sites had better protection from later tumor challenge than those receiving single vaccinations. Of the animals receiving vaccination at multiple sites, those vaccinated in the site of tumor challenge (floor of the mouth) had more protection than those not vaccinated at the site. CONCLUSIONS: Mice vaccinated at multiple draining lymph node sites were better primed against tumor challenge than mice receiving single inoculations. Vaccination strategies that included the challenge site (floor of the mouth) and the nodes near this site were optimal.

Animals↗

Policies to influence the spatial distribution of physicians: a conceptual review of selected programs and empirical evidence.

To increase the usefulness of existing physician location literature for policy evaluation, literature is grouped into intraurban and urban-rural studies. A conceptual overview of physician location literature is presented. Consensus results, if any, are discussed. A list of hypotheses suggested by the literature is then utilized in a discussion of economic social, prior exposure, and professional development incentives embodied in selected public and private sector programs. Programs are evaluated by type of incentive mechanism and geographic target area to determine if present program structures are based on a solid empirical foundation. This assessment indicates that, in general, use of prevalent location incentive mechanisms is not justified by a consensus of empirical evidence.

Economics↗

The determinants of spatial distribution of hospital utilization in a region.

This article presents a series of models for explaining hospital utilization. The models belong to the multinomial logit class, which relate the probability of hospital selection to factors that include travel time between patients and hospitals, hospital attractiveness factors, physician characteristics, and patient characteristics. Separate models for different population groups (sex, age, socioeconomic classes) and medical services (general medicine, obstetrics, pediatrics, psychiatry, and general surgery) are estimated and compared with the general hospital model. The results, which are based on an extensive data base and new estimation procedures, are superior to those of past studies. A number of differences between utilization patterns for the various populations are also observed.

Adolescent↗

The spatial distribution of pancreatic islets follows a universal power law.

In a previous report we quantified the apparently complex and irregular distribution of pancreatic islets in the guinea pig by showing that they formed a set of cluster or correlation dimension approximately 2.5. Here we show that this distribution holds in a wide range of mammalian species and through ontogenetic development in the guinea pig. These results strongly suggest that islet formation follows an iterative or fractal rule which is universal among mammals.

Animals↗

The spatial distribution and size of rook (Corvus frugilegus) breeding colonies is affected by both the distribution of foraging habitat and by intercolony competition.

Explanations for the variation in the number of nests at bird colonies have focused on competitive or habitat effects without considering potential interactions between the two. For the rook, a colonial corvid which breeds seasonally but forages around the colony throughout the year, both the amount of foraging habitat and its interaction with the number of competitors from surrounding colonies are important predictors of colony size. The distance over which these effects are strongest indicates that, for rooks, colony size may be limited outside of the breeding season when colony foraging ranges are larger and overlap to a greater extent.

Animals↗

The nature and spatial distribution of amino acid substitutions conferring resistance to neutralizing monoclonal antibodies in human rhinovirus type 2.

A total of 38 neutralization escape mutant viruses have been selected from a cloned stock of human rhinovirus serotype 2 (HRV-2), using either of two monoclonal antibodies (MAbs) which recognize overlapping epitopes as judged by competition binding. The mutant viruses were analysed for their sensitivity to a panel of antiviral MAbs by antibody binding and virus neutralization assays. The position and nature of the selected mutations was determined by sequencing of the virus RNAs, and the location of the substituted amino acids on the three-dimensional structure of the virus predicted from the co-ordinates determined for the closely related HRV-1A. Escape from neutralization could be attributed to single amino acid substitutions in all but one case, which had a deletion of four amino acids. In all cases in which the same mutation was found more than once, these mutations were transitions. The ratio of transition to transversion mutations was about 5:1 overall or about 1.7:1 if only unique substitutions are considered. Each antibody selected for a discrete cluster of mutations and the area of these clusters was considerably less than that determined to be in contact with antibodies from X-ray crystallographic analyses of antibody/protein complexes. One mutation did not occur within the cluster of others selected with the same antibody. This substitution occurred at the base of a small loop and may cause conformational changes at the virus surface.

Amino Acids↗

Spatial distribution of nitrogen on grazed karst landscapes.

The impact on water quality by agricultural activity in karst terrain is an important consideration for resource management within the Appalachian region. Karst areas comprise about 18% of the region"s land area. An estimated one-third of the region"s farms, cattle, and agricultural market value are located on karst terrain. Mean nitrate concentrations in several karst springs in southeastern West Virginia exhibit a strong linear relationship with the percentage of agriculture land cover. Development of best management practices for efficient nitrogen (N) use and reduction of outflow of N to water from karst areas requires knowledge about N dynamics on those landscapes. Water extractable NO3-N and NH4-N were measured along transects at four soil depths in two grazed sinkholes and one wooded sinkhole. Distribution of soil NO3-N and NH4-N were related to frequency of animal presence and to topographic and hydrologic redistribution of soil and fecal matter in the grazed sinkholes. Karst pastures are characterized by under drainage and funneling of water and contaminants to the shallow aquifer. Control of NO3-N leaching from karst pasture may depend on management strategies that change livestock grazing behavior in sinkholes and reduce the opportunity for water and contaminants to quickly reach sinkhole drains.

Agriculture↗