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J F Whitfield

Publications and source records attributed to J F Whitfield.

261 records · Page 15Linked to original sources
PubMedDate not supplied

Identification of lactate, threonine and alanine in rat thymus and tumorigenic lymphoid cells using 1H 2-D COSY NMR spectroscopy.

One- and two-dimensional 1H NMR spectra were obtained for normal murine thymus and malignant lymphoma tissue, as well as for the supernatant fractions from high speed centrifugal separations. Crosspeaks in the two-dimensional spectra resembled those reported by others for adenocarcinoma and leukemic lymphoblast cells, assigned tentatively to the carbohydrate fucose. However, for the present systems, spectral analysis and the spectral response to addition of known compounds led to assignment of the crosspeaks as follows: 1.33-4.12 ppm, lactate anion; 1.33-4.26 ppm, threonine; 1.48-3.78 ppm, alanine. Differences between the NMR data for the normal and malignant specimens were only in the relative intensities of the peaks. No peaks characteristic of fucose were found in spectra of cytosol, tissue or membrane lipids. Thus, the NMR data for malignant lymphoma cells are significantly different from those for adenocarcinoma and leukemic lymphoblasts. The NMR characteristics of different types of cancer cell must be individually determined.

Alanine↗
PubMedDate not supplied

The M1 subunit of rat liver ribonucleotide reductase appears to be modified by ubiquitination.

Using a combination of immunoblotting, double immunoprecipitation, immunoglobulin-affinity chromatography, and isoelectrofocusing, we have been able to identify a group of proteins that display CDP-reductase activity and contain antigenic epitopes recognized by anti-ribonucleotide reductase M1 subunit and anti-ubiquitin antibodies. In the cytoplasm of rat liver cells, we could detect a total of five proteins with molecular masses of 92, 89, 56, 45, and 37 kilodaltons which reacted with the anti-M1 subunit serum. All of them, except the 89-kilodalton protein (the nascent unmodified M1), were also recognized by the anti-ubiquitin antibody. In normal liver cells, all of the apparently ubiquitinated species of the M1 protein were found in the cytoplasm, but not in the nuclear envelope associated pool of the enzyme. However, we did not detect ubiquitinated M1 protein fragments in the cytoplasm of Morris hepatoma 5123tc. The level of the apparently ubiquitinated fragments of the M1 subunit increased in parallel to the DNA-synthetic activity of normal liver cells, suggesting that ubiquitination plays a key role in the regulation of the activity of the enzyme during the cell cycle.

Amino Acid Sequence↗
PubMedDate not supplied

The parathyroid hormones: bone-forming agents for treatment of osteoporosis.

This is a 3-part article. Part 1 is an overview of bone formation and resorption and the consequences of estrogen loss on bone. Part 2 comprehensively reviews the most current data on the ability of a family of potent osteoblast-stimulating bone-builders, the native 84-amino-acid parathyroid hormone (PTH), and certain of its 31- to 38- amino-acid fragments to stimulate the growth of animal and human bones. These PTHs are currently in, or about to enter, clinical trial as treatment for postmenopausal osteoporosis. Part 3 provides a detailed consideration of how these PTHs might stimulate bone growth via PTH receptor signaling.

Animals↗
PubMedDate not supplied

Characterization of the mitogenic signal from an oncogene ras protein.

Wild-type or cellular RAS proteins function at the end of the G1 phase of the cell cycle, but they cannot signal quiescent cells to start cycling. By contrast, the oncogenic or "activated" RAS proteins produced by certain mutant ras genes can start quiescent cells cycling and appear to be involved in a large fraction of human cancers. One of these "activated" RAS proteins is the temperature-sensitive viral K-RAS protein produced by tsKSV-NRK rat kidney fibroblasts. Reactivating this viral K-RAS protein in serum-starved quiescent cells by lowering the temperature from a non-permissive 41 degrees C to a permissive 36 degrees C is a powerful mitogenic signal which starts the progression of cells through the various stages of the cell cycle even in the absence of serum growth factors. This first signal is associated with transient surges of cytosolic Ca2+ and membrane-associated protein kinase C activity, but is not mediated by signals from the protein-tyrosine kinase receptors of known K-RAS-induced autocrine mitogens such as TGF alpha and PDGF. While the importance of the Ca2+ transient is uncertain, the transient surge of membrane-associated protein kinase C activity appears to be involved in the process by which the viral RAS protein triggers the G0 to G1 transition. The need for the viral K-RAS protein does not end with this first signal. The protein also operates briefly at the end of the G1 phase and then, after chromosome replication, it also stimulates events necessary for the initiation of mitosis.

Animals↗