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Biomedical subjects

D Fast

Publications and source records attributed to D Fast.

13 recordsLinked to original sources

Noninvasive localization of tumors by immunofluorescence imaging using a single chain Fv fragment of a human monoclonal antibody with broad cancer specificity.

BACKGROUND: A single chain antibody fragment, NovoMAb-G2-scFv, derived from a human anti-tumor monoclonal antibody recognizes tumor antigen molecules expressed on a wide variety of human cancers including melanoma, breast carcinoma, colon adenocarcinoma, squamous cell carcinoma, lung carcinoma, and prostate carcinoma. This study was designed to evaluate the use of a NovoMab-G2-scFv/cyanine fluorochrome (Cy5.5.18) conjugate as diagnostic tool for in vivo imaging of tumors. METHODS: The NovoMab-G2-scFv-Cy5 complex was administered to athymic mice injected subcutaneously with human melanoma tumor cells, and the distribution of fluorescence was imaged noninvasively using a charge-coupled device camera. Images were acquired 2, 6, 12, 24, 48, and 72 hours after injection. RESULTS: Fluorescence was detected at the tumor site after injection of NovoMab-G2-scFv-Cy5 but not after injection of a labeled irrelevant control antibody fragment. Fluorescence from the tumor site peaked 2 hours after injection and gradually declined, reaching a minimum 72 hours after injection. Fluorescence was also apparent in the kidneys, indicating clearance of the complex through the kidneys. Results suggest that 16% and 73% of the antibody is located in the tumor and kidneys, respectively. Imaging of isolated organs confirmed the presence of the NovoMab-G2-scFv-Cy5 complex in tumors, kidneys, and liver. No fluorescence was observed in other organs. CONCLUSIONS: Specific binding of the antibody-dye complex to the tumor was observed, and the kinetics of binding to tumors and kidneys were determined. These results suggest that the NovoMab-G2-scFv-Cy5.5 complex may be used for noninvasive tumor localization.

Animals↗

Design considerations for a transcranial Doppler coupled to a stereotactic position arm.

We present the localization error analysis for a stereotactic positioning arm, transcranial Doppler (TCD) system. Localization displacement errors were determined with a custom phantom head. A bubble apparatus was built to measure sample volume (SV). From interface plane relationships, biological material properties, and human computerized tomography (CT) scan data, an algorithm for computing the actual TCD signal path was developed. Localization resolution was diminished by constraints intrinsic to the TCD instrument (+/-1 mm) and the positioning arm (1.9+/-0.9 mm). The overall SV localization error ranged from 3.3 mm from the target, to complete signal loss at a critical cumulative angle of 31, one third of which may be reached at the TCD probe/skin interface. Any stereotactic ultrasound system must include correction for the beam path. The "failed ultrasound window," may be predicted by signal loss based on refraction alone. The use of stereotactic TCD may enhance the clinical applications of TCD.

Equipment Design↗

Isolation of replication-competent molecular clones of visna virus.

Visna virus is the prototypic member of a subfamily of retroviruses responsible for slow infections of animals and humans. As a part of our investigation of the functions of viral gene products in virus replication, we have isolated three infectious molecular clones and determined the complete nucleotide sequences of two of the clones. We have also characterized the progeny of the biologically cloned viral stocks and of the infectious clones and document considerable heterogeneity in plaque size and antigenic phenotype of the former that is reduced to near homogeneity in the progeny of the infectious clones. It thus should now be possible to trace the emergence of antigenic variants of visna virus as well as ascribe defined functions to structural and regulatory genes of the virus in determining neurovirulence and the slow tempo of infection.

Amino Acid Sequence↗

Different hormonal requirements for androgen-independent growth of normal and tumor epithelial cells from rat prostate.

The proliferation of isolated normal prostate epithelial cells from rat and man is androgen-independent and requires cholera toxin, insulin, dexamethasone, epidermal growth factor (EGF) and one or more polypeptide factors that are concentrated in bovine neural tissue. The active agents in the neural tissue extract are heparin-binding polypeptides (prostatropins), the predominant form of which has a molecular weight of 17400 and an acetylalanine at the aminoterminus. Prostatropins supported a half-maximal increase in normal prostate epithelial cell number at 50 picomolar. The proliferation of primary and serially-cultured epithelial cells from androgen-responsive Dunning R3327 rat prostate tumors was also androgen-independent, but exhibited dramatic alterations in response to hormones that stimulated normal cell proliferation. At low cell density, androgen-independent growth of isolated tumor-derived epithelial cells was independent on cholera toxin, was stimulated by dexamethasone, required insulin and either EGF or prostatropin. The presence of either EGF or prostatropin masked the response to the other factor. In the absence of EGF, purified prostatropins supported a half-maximal increase in tumor cell number at 7 picomolar. Endogenous production of EGF-like and prostatropin-like factors or both was suggested by the reduced requirement for EGF and prostatropin at high prostate tumor cell density. These results suggest that anti-hormonal therapies against prostate tumor growth should be based on intervention with the activity of insulin (or insulin-like factors) or simultaneous intervention with both EGF and prostatropin (or their homologues).

Animals↗

The effect of dibutyryl cyclic adenosine-3'-5'-monophosphate on protein secretion from the rat exocrine pancreas in vitro.

1 The mechanism by which dibutyryl cyclic adenosine-3'-5'-monophosphate (dibutyryl cyclic AMP) potentiates the secretory effect of carbachol in rat exocrine pancreas was investigated. 2 Dibutyryl cyclic AMP potentiated the secretory effect of carbachol only at carbachol concentrations greater than or equal to 10(-7) mol/l; was independent of carbachol at concentrations greater than 10(-7) mol/l and was inversely proportional to extracellular [Ca2+]. 3 Carbachol increased and dibutyryl cyclic AMP reduced the rate of 45Ca efflux from the tissue. 4 A-23187 stimulated 3H-protein release in the presence of Ca2+ and this effect was potentiated by dibutyryl cyclic AMP; the degree of potentiation was inversely proportional to extracellular [Ca2+]. At 10(-3) mol/l [Ca2+] the potentiation occurred only at ionophore concentrations less than or equal to 10(-6) mol/litre. 5 These results support the hypothesis that dibutyryl cyclic AMP potentiates the effect of secretagogues in rat exocrine pancreas by maintaining an elevated intracellular calcium concentration. It does so by inhibiting Ca2+ efflux. The results also suggest that the limiting factor in carbachol-stimulated secretion, at all concentrations of carbachol, is intracellular [Ca2+].

Animals↗

Sporulation synchrony of Saccharomyces cerevisiae grown in various carbon sources.

Sporulation of several strains of Saccharomyces cerevisiae grown in a variety of carbon sources that do not repress the tricarboxylic acid cycle enzymes was more synchronous than the sporulation of cells grown in medium containing dextrose which does repress those enzymes. Dextrose-grown cells showed optimal sporulation synchrony when inoculated into sporulation medium from early stationary phase when the dextrose in the medium is exhausted. Logarithmic-phase cells grown in either non-fermentable carbon sources (acetate and glycerol) or a fermentable carbon source that does not repress tricarboxylic acid cycle enzymes (galactose) sporulated more synchronously than the early stationary-phase dextrose cells. Attempts were made to sporulate cells taken from both complex and semidefined media. The semidefined acetate medium failed to support the growth of a number of strains. However, cells grown in the complex acetate medium, as well as both complex and semidefined glycerol and galactose media, sporulated with better synchrony than did the dextrose-grown cells.

Acetates↗

Effect of dibutyryl cyclic adenosine 3',5'-monophosphate, theophylline, and other nucleotides upon calcium and phosphate metabolism.

The effect of dibutyryl cyclic adenosine 3',5'-monophosphate upon calcium and phosphate metabolism in thyroparathyroidectomized rats was undertaken in an effort to clarify the possible role of adenosine 3',5'-monophosphate (3',5' AMP) in parathyroid hormone action. The infusion of dibutyryl cyclic 3',5' AMP at a rate of 3 mg/hr into thyroparathyroidectomized rats leads to changes in calcium, phosphate, and hydroxyproline excretion, and calcium and phosphate concentrations in plasma that are qualitatively similar to those induced by parathyroid hormone given at a rate of 5 mug/hr. The effect of dibutyryl cyclic 3',5' AMP upon calcium and hydroxyproline mobilization from bone is blocked by thyrocalcitonin administration in the same way that thyrocalcitonin blocks PTH effects. Other closely related nucleotides do not act in the same way. These data indicate that dibutyryl cyclic 3',5' AMP produces effects similar to parathyroid hormone in thyroparathyroidectomized rats, and support the notion that 3',5' AMP is an intermediate in the mechanism of PTH action. However, the changes in magnesium and potassium excretion are different after dibutyryl cyclic 3',5' AMP infusion from those seen after PTH infusion. Also, theophylline was found to potentiate the action of smaller doses of dibutyryl 3',5' AMP, but not that of PTH.

Adenine Nucleotides↗

Ritualistic use of the holly Ilex guayusa by Amazonian Jívaro Indians.

In Amazonian Peru and Ecuador leaf decoctions of the rainforest holly Ilex guayusa with high caffeine concentrations are used as a morning stimulant. After daily ingestion, ritualistic vomiting by male Achuar Indians, better known as Jívaros, reduces excessive caffeine intake, so that blood levels of caffeine and biotransformed dimethylxanthines do not cause undesirable CNS and other effects. Emesis is learned and apparently not due to emetic compounds.

Caffeine↗