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Biomedical subjects

J B Mitchell

Publications and source records attributed to J B Mitchell.

At least 379 records · Page 21Linked to original sources
PubMed1976

A day school approach to aggressive adolescents.

A day school for aggressive adolescents, organized cooperatively by a school system, a youth guidance center, and a state hospital, is providing an effective alternative to institutionalization. Education and therapy are combined in a supportive setting.

Adolescent↗
PubMedDate not supplied

Modulation of protein expression and activity by radiation: relevance to intracoronary radiation for the prevention of restenosis.

Restenosis is a common complication of percutaneous transluminal coronary angioplasty. Recent studies have demonstrated a striking reduction in the neointimal hyperplasia characteristic of restenosis following intracoronary radiation (IR), but the mechanisms by which radiation reduces neointima formation following balloon overstretch injury are not elucidated fully. In addition to direct antimitotic effects mediated via oxygen free radicals, ionizing radiation can induce the expression of numerous genes and thereby mediate indirect effects. Additionally, IR prevents restenosis at the cost of decreased healing and increased thrombosis, and we suggest that these adverse reactions can be modulated by adjunct pharmacology or gene-based strategies. This review discusses several genes and proteins modulated by radiation in the context of arterial injury, and their possible therapeutic relevance.

Animals↗
PubMedDate not supplied

The relationship between the sequence identities of alpha helical proteins in the PDB and the molecular similarities of their ligands.

This paper considers the relationship between the percentage sequence identities of protein chains and the molecular similarities of the ligands they bind. Among a set of alpha helical proteins from the PDB, it is found that related proteins tend to bind similar ligands. Furthermore, the property of binding similar ligands can be used to define the categories of "like" and "unlike" pairs of protein chains, separated by an approximate cutoff at a sequence identity of, or somewhat above, 45%. Similarly, the property of binding related protein chains can be used to define "low" and "high" similarity pairs of ligand residues, with a cutoff at a Tanimoto score of 0.70. The ligands bound to two "like" protein chains are five times more likely to be of high similarity than would be expected if protein sequence identity and ligand molecular similarity were independent variables. Nonetheless, the nature of the PDB means that it is unclear whether the same conclusions would be reached with a data set representing an unbiased sample of all protein-ligand complexes in a living cell. The construction of an appropriate data set for such a study represents a significant challenge.

Amino Acid Sequence↗
PubMedDate not supplied

Involvement of mesolimbic dopamine neurons in sexual behaviors: implications for the neurobiology of motivation.

Mesencephalic dopamine-containing neurons that innervate limbic regions, notably nucleus accumbens, are thought to be involved in the control of a variety of species-typical behaviors such as male copulatory behavior, feeding and drinking as well as of behaviors reinforced by many drugs abused by humans. While it is generally agreed that these neurons are an important link in the brain circuitry that mediates these behaviors, their precise function remains a source of conjecture. The present article reviews evidence implicating the mesoaccumbens dopamine projection in sexual behaviors and discusses some of the issues that have contributed to the uncertainty over the exact role of this system in these and other species typical behaviors. This review also describes approaches we have been using in an attempt to address these issues and summarizes recent findings we believe provide important insights into mesoaccumbens dopamine function and the neurobiology of motivation.

Animals↗
PubMedDate not supplied

Hyperthermic sensitization by the radical initiator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). I. In vitro studies.

AAPH (2,2'-azobis-(2-amidinopropane dihydrochloride)) is a water-soluble, heat-labile azo compound which undergoes thermal decomposition to produce carbon-centred free radicals. These carbon-centred radicals might be directly cytotoxic or may react with oxygen to produce potentially cytotoxic alkoxyl and peroxyl radicals. The rate of free radical production as a result of AAPH thermal decomposition increases with increasing temperature. We have evaluated the efficacy of AAPH as a heat sensitizer for Chinese hamster V79 cells by the clonogenic assay. AAPH (50 mM) was not cytotoxic to V79 cells at 37 degrees C for exposures up to 3 h. In contrast, AAPH (50 mM) was found to markedly sensitize cells exposed to 42, 43 and 45 degrees C. For a 75 min exposure to 42 degrees C alone, cell survival was reduced to 9 x 10(-1); however, a 75 min exposure at 42 degrees C+AAPH resulted in survival of 5.5 x 10(-4). For 43 and 45.5 degrees C heating, cell survival was potentiated by AAPH at the 1% survival level by 4.1 and 1.4-fold, respectively. AAPH was also found to sensitize both hypoxic cells and thermotolerant cells. These findings would encourage in vivo evaluation of AAPH (or analogues) as a temperature-dependent heat sensitizer. AAPH represents a new class of heat sensitizers which may have use in unravelling the mechanism(s) of heat killing and may have utility in local hyperthermia treatment.

Amidines↗
PubMedDate not supplied

A local hyperthermia treatment which enhances antibody uptake in a glioma xenograft model does not affect tumour interstitial fluid pressure.

Solid tumours have an elevated interstitial fluid pressure (IFP) due to the lack of normal lymphatics, increased permeability of tumour vasculature and an expanding cell population within a potentially limited space. This elevated IFP has been proposed to be an important barrier to the delivery of drugs and marcromolecules. We have demonstrated that local hyperthermia (4 h, 41.8 degrees C) is capable of significantly enhancing the uptake of radiolabelled monoclonal antibodies (mAbs) in D-54 MG glioma xenografts grown subcutaneously in athymic mice. To determine if this increased uptake was attributable to alterations in the tumour IFP, pressure measurements using the wick-in-needle technique were made in tumours after hyperthermia treatment. These pressure measurements were taken at various time points from 4 to 90 h following the initiation of the hyperthermia and compared with pressures taken concurrently in untreated tumours. In addition, pressures were measured following a 2 h, 41.8 degrees C hyperthermia treatment, a protocol which does not result in elevated uptake of radiolabeled mAbs. No significant differences were seen at any time point in IFP measured in the tumours receiving either hyperthermia treatment when compared with untreated tumours. Thus, we conclude that the mechanism by which this hyperthermia regimen enhances mAb uptake in this human glioma xenograft model is not due to alternations in tumour IFP.

Animals↗