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T Volk

Publications and source records attributed to T Volk.

At least 73 records · Page 4Linked to original sources
PubMed1995

A calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells.

We recently reported that M-1 mouse cortical collecting duct cells show nonselective cation (NSC) channel activity (Proc. Natl. Acad. Sci. USA 89:10262-10266, 1992). In this study, we further characterize the M-1 NSC channel using single-channel current recordings in excised inside-out patches. The M-1 NSC channel does not discriminate between Na+, K+, Rb+, Cs+, and Li+. It has a linear I-V relation with a conductance of 22.7 +/- 0.5 pS (n = 78) at room temperature. The Pcation/P(anion) ratio is about 60 and there is no measurable conductance for NMDG, Ca2+, Ba2+, and Mn2+. Cytoplasmic calcium activates the M-1 NSC channel at a threshold of 10(-6) M and depolarization increases channel activity (NPo). Cytoplasmic application of adenine nucleotides inhibits the M-1 NSC channel. At doses of 10(-4) M and 10(-3) M, ATP reduces NPo by 23% and 69%, respectively. Furthermore, since ADP (10(-3) M) reduces NPo by 93%, the inhibitory effect of adenine nucleotides is not dependent on the presence of a gamma-phosphoryl group and therefore does not involve protein phosphorylation. The channel is not significantly affected by 8-Br-cGMP (10(-4) M) or by cGMP-dependent protein kinase (10(-7) M) in the presence of 8-Br-cGMP (10(-5) M) and ATP (10(-4) M). The NSC channel is not sensitive to amiloride (10(-4) M cytoplasmic and/or extracellular) but flufenamic acid (10(-4) M) produces a voltage-dependent block, reducing NPo by 35% at depolarizing voltages and by 80% at hyperpolarizing voltages. We conclude that the NCS channel of M-1 mouse cortical collecting duct cells belongs to an emerging family of calcium-activated and nucleotide-sensitive nonselective cation channels. It does not contribute to amiloride-sensitive sodium absorption and is unlikely to be a major route for calcium entry. The channel is normally quiescent but may be activated under special physiological conditions, e.g., during volume regulation.

Animals↗
PubMed1995

Interactions of CO2, temperature and management practices: simulations with a modified version of CERES-Wheat.

A new growth subroutine was developed for CERES-Wheat, a computer model of wheat (Triticum aestivum) growth and development. The new subroutine simulates canopy photosynthetic response to CO2 concentrations and light levels, and includes the effects of temperature on canopy light-use efficiency. Its performance was compared to the original CERES-Wheat V-2 10 in 30 different cases. Biomass and yield predictions of the two models were well correlated (correlation coefficient r > 0.95). As an application, summer growth of spring wheat was simulated at one site. Modeled crop responses to higher mean temperatures, different amounts of minimum and maximum warming, and doubled CO2 concentrations were compared to observations. The importance of irrigation and nitrogen fertilization in modulating the wheat crop climatic responses were also analyzed. Specifically, in agreement with observations, rainfed crops were found to be more sensitive to CO2 increases than irrigated ones. On the other hand, low nitrogen applications depressed the ability of the wheat crop to respond positively to CO2 increases. In general, the positive effects of high CO2 on grain yield were found to be almost completely counterbalanced by the negative effects of high temperatures. Depending on how temperature minima and maxima were increased, yield changes averaged across management practices ranged from -4% to 8%.

Agriculture↗
PubMed1995

An approach to crop modeling with the energy cascade.

Use of plants in advanced life support requires models of crop growth to analyze data, to evaluate areas for improvement, and, for design and engineering, to predict the gas exchanges of crops. We used data from experiments at Utah State University and the Kennedy Space Center for wheat (Triticum aestivum L.) and examined it for time dependence of the major three components in the energy cascade: photosynthetic photon absorption, canopy quantum yield, and carbon use efficiency. From the Utah State data, we developed a model with a total of five trends: absorption increasing until canopy closure, then constant; quantum yield as constant, then decreasing during senescence; carbon use as constant. This system probably is the lower limit of simplicity to which a model can be reduced and yet provide substantial utility. We demonstrated this utility by using the model to predict photosynthesis and respiration for experiments at Kennedy Space Center. The most uncertainty arose in predicting a start time for the senescent decrease of canopy quantum yield. The model should be generally applicable to other crops grown in controlled environments, as a generic tool for the design of life support systems.

Biomass↗
PubMed1994

Reduction of intratumoral pH by the mitochondrial inhibitor m-iodobenzylguanidine and moderate hyperglycemia.

The interstitial pH of RIF-1 tumors was selectively lowered by i.p. administration of the mitochondrial inhibitor meta-iodobenzylguanidine (MIBG; 40-100 mg/kg), supported by sustained moderate hyperglycemia (plasma glucose concentration, 14 mM) in rats or by a single i.p. bolus injection of glucose (1.5 g/kg) in mice. Responses were evaluated in a multicenter study by pH measurements with semimicroelectrodes and 31P magnetic resonance spectroscopy, by biochemical analysis of tissue and plasma levels of glucose and lactate, and by positron emission tomography analysis of 2-[18F]fluoro-2-deoxy-D-glucose uptake. In both schedules, treatment with MIBG and glucose reduced the mean intratumoral pH as recorded with semimicroelectrodes to 6.2. In the mouse model, treatment with MIBG plus glucose was accompanied by a 2-3-fold stimulation of 2-[18F]fluoro-2-deoxy-D-glucose uptake and a corresponding increase in tumor glucose content. Responses were maximal in male mice with tumors of 0.2-0.8 g. 31P magnetic resonance spectroscopy analysis revealed no changes in intracellular pH or metabolic status, indicating that only extracellular pH was affected. MIBG was synergistic with bolus or continuous glucose administrations by a dual mechanism. The drug reduced by up to 5-fold the amount of glucose required for effective reduction of intratumoral pH and promoted the availability of (extra) glucose to tumor tissue in a stress-related, sympathomimetic response. Moreover, by converting oxic tumor cells into functionally hypoxic cells, combined treatment resulted in a more homogeneous decrease in intratumoral pH which included better perfused peripheral tumor areas. The effects of combined treatment on tumor glucose metabolism could be monitored noninvasively by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography analysis.

3-Iodobenzylguanidine↗
PubMed1994

A central role for epidermal segment border cells in the induction of muscle patterning in the Drosophila embryo.

The correct patterning of muscles in the Drosophila embryo depends on the migration of developing muscles over the ectoderm and on the attachment of these muscles to specific attachment sites. We investigate the mechanisms that are involved in this process and describe experiments that allow a genetic dissection of the role of the ectoderm in muscle migration and attachment. We show that cells along the segmental border in the ectoderm are used by the developing muscles to reach their attachment sites. These segment border cells are recognized by dissociated myotubes in single suspensions in culture. Thus, developing muscles have properties that allow the specific recognition of the segment border cells and migrate to attach to these cells. The segment border cells are absent in the mutant wingless and naked. In these mutants, the muscles are severely disorganized. We show that this is not a mere consequence of disruption of the epidermis, since, in the mutant patched, where segmental patterning is affected, the segment border cells are present near their normal position; the muscles in this mutant are relatively organized. Similarly, in the mutant lines where ectopic segment border cells are present, the observed muscle derangement correlates well with the ectopic attachment sites that are present. Finally, we have analyzed mutants at the stripe locus and have shown that lethal alleles disrupt muscle organization during embryogenesis. Enhancer-trap alleles of stripe that we have analyzed show reporter gene expression in the segment border cells. Our results indicate a role for the segment border cells in guidance of migrating muscle fibers to their attachment sites.

Animals↗
PubMed1993

Effect of glucose-mediated pH reduction and cyclophosphamide on oxygenation of transplanted rat tumors.

PURPOSE: Glucose-mediated reduction of tumor pH is under investigation as a means to improve the therapeutic index of anticancer agents. An improvement of glucose supply to tumors is, however, likely to influence various metabolic and pathophysiological parameters apart from pH which, in turn, could modulate H+ ion-mediated effects. As a first step to identify changes in these parameter, we have investigated the effect of glucose-mediated pH reduction on oxygenation of malignant tissues either per se or in combination with a pH-sensitive drug, cyclophosphamide. METHODS AND MATERIALS: H+ ion and oxygen-sensitive semi-microelectrodes were used to measure pH and pO2 in transplanted TV1A and AH13r rat tumors at normoglycemia and following high-dose intravenous glucose infusion. RESULTS: In both tumors analyzed, pH reduction was accompanied by a decrease in pO2. In TV1A tumors, for example, the mean (median) pO2 decreased from 8.2 mm Hg (3.7 mm Hg) to 3.9 mm Hg (1.7 mm Hg) at 2 hr and 2.9 mm Hg (1.9 mm Hg) at 24 hr, respectively, after raising the plasma glucose concentration to 25 +/- 2 mmol/l. At the same time points, the mean pH had declined from 6.89 to 6.29 and 6.24, respectively. The class of pO2 readings < 5 mm Hg increased from a pretreatment value of 65% to approximately 90% at 24 hr. In contrast, cyclophosphamide treatment resulted in improved oxygenation of AH13r tumors, an effect first observed at 24 hr after drug administration. When both modalities were combined, cyclophosphamide partly prevented the acidosis-associated decrease in oxygen partial pressure. CONCLUSION: The results of this study indicate that, within the context of the therapeutic approach used, cytotoxic agents should be employed which are more active against hypoxic than against well-oxygenated cells. In particular, glucose-mediated reduction of oxygen partial pressure in malignant tissues may be exploited to increase the fraction of hypoxic cells prior to administration of drugs activated in hypoxic cells by reductive metabolism (bioreductive agents).

Animals↗
PubMed1993

Comments on "Bioprocessing in space"

An analysis developed by Westgate et al. for the digestible energy of edible and inedible biomass, including hydrolysis and fermentation, is reexamined with state-of-the-art values for the harvest index of hydroponic crops.

Biomass↗
PubMed1993

pH in human tumour xenografts: effect of intravenous administration of glucose.

pH frequency distributions of tumours grown s.c. from 30 human tumour xenograft lines in rnu/rnu rats were analysed with the use of H+ ion-sensitive semi-microelectrodes prior to and following stimulation of tumour cell glycolysis by i.v. infusion of glucose. At normoglycemia, the average pH of the tumours investigated was 6.83 (range, 6.72-7.01; n = 268). Without exception, all xenografts responded to the temporary increase in plasma glucose concentration (PGC) from 6 +/- 1 to 30 +/- 3 mM by an accumulation of acidic metabolites, as indicated by a pH reduction to an average value of 6.43 (range, 6.12-6.78; n = 292). This pH value corresponds to a ten-fold increase in H+ ion activity in tumour tissue as compared to arterial blood. Tumour pH approached minimum values at 2-4 h after the onset of glucose administration and could be maintained at acidic levels for 24 h by controlled glucose infusion. Irrespective of pH variations between tumours grown from individual xenograft lines, there was no major difference in pH response to glucose between the four main histopathological tumour entities investigated, i.e. breast, lung and gastrointestinal carcinomas, and sarcomas. In tumours from several xenograft lines, an increase in blood glucose to only 2.5-times the normal value (14 mM) was sufficient to reduce the mean pH to 6.4. Glucose-induced acidosis was tumour-specific. The pH frequency distributions in liver, kidney and skeletal muscle of tumour-bearing rnu/rnu rats were only marginally sensitive to hyperglycemia (average pH, 6.97 vs normal value of 7.14). Tumour-selective activation of pH-sensitive anti-cancer agents, e.g. alkylating drugs, acid-labile prodrugs or pH-sensitive immunoconjugates may thus be feasible in a wide variety of human cancers.

Animals↗
PubMed1992

pH in human tumor xenografts and transplanted rat tumors: effect of insulin, inorganic phosphate, and m-iodobenzylguanidine.

Various strategies to improve the therapeutic index of anticancer agents aim at inducing, by stimulation of aerobic glycolysis, temporary pH differences between malignant and normal tissues which can be exploited to activate cytotoxic agents selectively in tumors. We have investigated whether the pH reduction induced by glucose, the "drug" commonly used to increase lactic acid production in malignant tissues, can be augmented by pharmacological manipulation of tumor cell glycolysis. At normal plasma glucose concentration (6 +/- 1 mM), inorganic phosphate, a modifier of hexokinase and phosphofructokinase activity, had no effect on pH in two transplanted rat tumors and a human tumor xenograft line (average pH, 6.80; range, 6.65-6.95). When plasma glucose concentration was raised to 30 +/- 3 mM by i.v. infusion of glucose, inorganic phosphate reduced the pH in those tumors which exhibited only a moderate pH response to glucose per se (mean pH, 6.60) to an average value of 6.20 (range, 6.05-6.35). In the same setting, insulin, continuously infused at dose rates up to 600 milliunits/kg body weight/min, did not result in acidification of tumor tissue exceeding that induced by glucose alone. However, the H+ ion activity in both transplanted rat tumors and human tumor xenografts was increased by m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. For example, at normoglycemia, MIBG reduced the mean pH in a human mesothelioma xenograft from 6.90 to 6.70. This pH value was further reduced to 6.20 by simultaneous low-dose i.v. glucose infusion (plasma glucose concentration, 14 +/- 3 mM). The acidosis induced by inorganic phosphate and MIBG was tumor specific. Normal tissues of tumor-bearing hosts were only marginally sensitive to hyperphosphatemia or MIBG administration. These results indicate that the known stimulatory effect of exogenous glucose on lactic acid production in malignant tumors in vivo can be further accentuated or, as in the case of MIBG, partially replaced by pharmacological manipulation of aerobic glycolysis using clinically established drugs.

3-Iodobenzylguanidine↗
PubMed1992

Metabolic response of AH13r rat tumours to cyclophosphamide as monitored by pO2 and pH semi-microelectrodes.

The composition of the microenvironment has an important influence on the cellular response to cytotoxic agents. Using pH and pO2 semi-microelectrodes, we have monitored metabolic changes in AH13r rat tumours as a function of time after subcurative chemotherapy. Prior to therapy, tumours contained large areas considered hypoxic (mean pO2 approximately 4 mmHg) and are characterised by a marked accumulation of acidic metabolites (mean pH 6.65). Administration of cyclophosphamide (40 mg/kg body weight) resulted in tumour regression to 15% of pretreatment volumes and a growth delay of 12 days. Concomitant with volume reduction, tumours became reoxygenated (mean pO2 approximately 7 mmHg), with maximum values being reached within 2-4 days, paralleled by a shift of pH to more alkaline values (0.17 U on average). These changes coincided with the development of subtotal necrosis. During early tumour regrowth, the pH and pO2 histograms returned to control values. These data corroborate and extend the results of previous studies in which noninvasive techniques had been applied for the monitoring of treatment-induced metabolic changes in malignant tumours in vivo. In addition, these results support the notion that the effectiveness of anticancer therapy might be improved by selecting and scheduling therapeutic agents in consideration of physiological changes caused by preceding courses of treatment.

Animals↗
PubMed1992

A new member of the spectrin superfamily may participate in the formation of embryonic muscle attachments in Drosophila.

Myotube migration and the formation of muscle attachments are crucial events for the proper development of muscle patterning in the Drosophila embryo. This paper describes the identification of a new embryonic muscle-specific protein, MSP-300, in Drosophila. This protein is initially expressed by muscle precursors at muscle-ectoderm and muscle-muscle attachment sites. As development continues, MSP-300 becomes associated with muscle myofibrillar network. Studies of the subcellular localization of this muscle-specific protein in primary embryonic cultured myotubes show that MSP-300 decorates actin filaments, and that it is specifically enriched in sites where actin microfilaments are linked to the plasma membrane. Migrating myotubes exhibit high levels of this protein at their leading edge while, in myotubes that have already developed sarcomeric architecture, the protein is localized mainly at the Z-discs. Sequence of a partial 3.9 kb cDNA clone and molecular analysis of the predicted protein sequence of this protein indicates that it encodes a high relative molecular mass protein (approximately 300 x 10(3), which exhibits at least five spectrin-like repeats. Several properties are shared by MSP-300 and members of the spectrin superfamily: it is associated with actin microfilaments, its sequence exhibits spectrin-like repeats and it is localized at sites where actin is linked to the plasma membrane. This protein could have a developmental role in the formation of muscle-ectoderm attachments and may be involved in myotube migration on the ectoderm.

Amino Acid Sequence↗
PubMed1990

A role for integrin in the formation of sarcomeric cytoarchitecture.

We propose that integrins help to coordinate the differentiation of the internal, sarcomeric cytoarchitecture of a muscle fiber with its immediate environment and are essential for correct integration of muscle cells into tissue. We found that integrin alpha PS2 beta PS accumulated at contact regions of Drosophila embryo cells cultured in D-22 medium on Drosophila laminin. Myotubes formed, but subsequent addition of serum or fibronectin was needed for sarcomere formation: integrin and actin became concentrated at Z-bands; myosin and actin occurred between the Z-bands. This change failed to occur in the multinucleate myotubes derived from integrin beta PS null myospheroid mutants. In normal embryos/early larvae, integrin was located at Z-bands and at muscle insertions. Myogenesis and Z-bands were defective in myospheroid embryos. Attachment, spreading, and growth of myoblasts and neurons on the laminin substrate utilized different binding proteins and were independent of integrin.

Animals↗
PubMed1990

Cleavage of A-CAM by endogenous proteinases in cultured lens cells and in developing chick embryos.

We describe two truncated forms of A-CAM (N-cadherin) and present evidence suggesting that both forms are proteolytically derived from the intact A-CAM molecule. The first is a membrane-bound fragment of A-CAM displaying an apparent molecular weight of 78 kDa. This polypeptide, containing the C-terminal portion of the protein, may be generated in cultured chicken lens cells, either by a short treatment with trypsin-EGTA, or by endogenous proteinase(s) during incubation in low Ca2+ medium. Immunofluorescent labeling of normal and EGTA-treated cells indicated that the 78-kDa fragment is uniformly distributed over the cell surface. Moreover, staining of developing chick embryos with pairs of antibodies which distinguish the 78-kDa fragment from intact A-CAM indicated that, at early stages of sclerotome dissociation in developing somites, a truncated derivative of the molecule is generated. The second truncated form of A-CAM is a 97-kDa polypeptide which is constitutively released by cultured lens cells into the culture medium in the presence of normal medium. We present evidence that the 97-kDa molecule is proteolytically derived from A-CAM by the action of an endogenous proteinase. We discuss possible mechanisms leading to the formation of these two truncated derivatives and their possible involvement in the physiological modulation of A-CAM-mediated interactions.

Amino Acid Sequence↗
PubMed1990

Open systems living in a closed biosphere: a new paradox for the Gaia debate.

While energetically open, the biosphere is appreciably closed from the standpoint of matter exchange. Matter cycling and recycling is hence a necessary and emergent property of the global-scale system known as Gaia. But how can an aggregate of open-system life forms have evolved and persisted for billions of years within a planetary system that is largely closed to matter influx and outflow? The puzzling nature of a closed yet persistent biosphere draws our attention to the course of evolution of fundamental metabolic strategies and matter-capture techniques. It suggests a facet of the Gaia hypothesis, framed in terms of persistence. The oceans, atmosphere, soils and biota constitute a complex system which maintains and adjusts matter cycling and recycling within the constraints of planetary closure such that open-system forms of life can persist. This weaker version of the Gaia hypothesis may be useful because it readily lends itself to at least one form of test. What is the solution to the closed biosphere puzzle, and does it indicate that Gaia merits status as a discrete entity? We suggest several disciplines within the field of biology that might provide tools and perspectives toward reaching a solution. These disciplines include artificial closed ecosystems, prokaryote evolution, the nexus of thermodynamics and evolutionary biology, and hierarchy theory in ecosystem modeling and evolution theory.

Biological Evolution↗
PubMed1989

Transpiration during life cycle in controlled wheat growth.

We use a previously-developed model of wheat growth, which was designed for convenient incorporation into system-level models of advanced space life support systems. We apply the model to data from an experiment that grew wheat under controlled conditions and measured fresh biomass and cumulated transpiration as a function of time. We examine the adequacy of modeling the transpiration as proportional to the inedible biomass and an age factor, which varies during the life cycle. Results indicate that during the main phase of vegetative growth in the first half of the life cycle, the rate of transpiration per unit mass of inedible biomass is more than double the rate during the phase of grain development and maturation during latter half of the life cycle.

Biomass↗
PubMed1988

The modulation of cell adhesion molecule expression and intercellular junction formation in the developing avian inner ear.

The cells that constitute the membranous labyrinth in the vertebrate inner ear are all derived from a single embryonic source, namely, the otocyst. The mature inner ear epithelia contain different regions with highly differentiated cells, displaying a highly specialized cytoarchitecture. The present study was designed to determine the presence of adherens-type intercellular junctions in this tissue and study the expression of cell adhesion molecules (CAMs) associated with these junctions, namely, A-CAM and L-CAM, in the developing avian inner ear epithelia. The results presented here show that throughout the early otocyst, A-CAM is coexpressed with L-CAM. The formation of asymmetries between sensory and nonsensory areas in the epithelium is accompanied by the modulation of CAMs expression and the assembly of intercellular junctional complexes. A-CAM and L-CAM display reciprocal expression patterns, the former being expressed mostly in the mosaic sensory epithelium, while L-CAM becomes conspicuous in the nonsensory areas but its expression in the sensory region is markedly reduced. Adherens-type junctions and numerous desmosomes are found in the junctional complexes of early otocyst cells. The former persist to maturity of the various inner ear epithelia, whereas desmosomes disappear from junctional complexes of hair cells but remain in the intercellular junctional complexes of all other cell types in the membranous labyrinth. Thus, adherens type intercellular junctions comprise the only defined cytoskeleton-bound junction in mature hair cells. A-CAM-positive cells are also found in the region of the acoustic ganglion in early developmental stages but not in the mature neural elements.

Actins↗