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G R Anderson

Publications and source records attributed to G R Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Retrotransposon-like VL30 elements are efficiently induced in anoxic rat fibroblasts.

VL30 elements are a multigene family within the class of retroviruses and retrotransposons. We have characterized the response of normal rat fibroblasts to anoxia, in which endogenous VL30 element expression is strongly induced. Optimal induction up to 500-fold occurs under complete anoxia, although a lesser response is seen under atmospheres up to 2% oxygen. Phorbol esters and diacylglycerol, which induce mouse VL30 RNA approximately eightfold, show no effect on the rat VL30 system. The hypoxic conditions optimal for rat VL30 induction represent a mild cellular stress, with no reduction in cell viability during the induction period. Although the precise physiological role of this fibroblast response to temporary anoxia is unknown, it may occur during wound healing. The induction of VL30 by anoxia provides a unique model system wherein a member of the mammalian retrovirus/retrotransposon family is highly responsive to a common physiological signal.

Animals↗
PubMed1988

The major anoxic stress response protein p34 is a distinct lactate dehydrogenase.

Anoxic stress is a common physiological stress, but one with unusual and significant consequences. Anoxic stress results in efficient induction of gene amplification and also plays a controlling role in the production of angiogenesis factor by macrophages. Within tumor masses, cancer cells continue to proliferate under oxygen tensions substantially lower than seen in normal tissues. The molecular basis of the anoxic stress response has not been well characterized. The major anoxic stress protein in subconfluent cell cultures is a 34-kilodalton polypeptide which has been variously reported to be either a new isozyme of lactate dehydrogenase (LDH) or the conventional muscle-type lactate dehydrogenase. This protein is of particular interest since it is also found expressed at high levels in many human cancers and has been demonstrated to be an effective serum cancer marker. We have developed an affinity chromatography procedure for purification of the anoxic stress protein p34 which effectively separates this protein from LDH-5 as well as other standard LDH isozymes. Anoxic stress protein p34 was found to specifically interact with flavins and the cellular alarmone guanosine(5')tetraphospho(5')guanosine, and also to interact with certain nucleic acids. The properties of this protein suggest that its overall role in the anoxic stress response may be in the coordination of a number of cellular systems.

Anaerobiosis↗
PubMed1988

Harvey sarcoma virus genome contains no extensive sequences unrelated to those of other retroviruses except ras.

The Harvey murine sarcoma virus genome contains two rat-derived sets of genetic information recombined with the Moloney mouse leukemia virus. The rat sequences represent a ras oncogene and a rat VL30 element. The VL30 sequences have several discrete regions of similarity with retroviral sequences which were detected by searching a protein database for similarities with predicted polypeptide sequences from the VL30 regions. On the 5' side, the most similar sequences were those of feline sarcoma viruses; on the 3' side, murine leukemia viruses were the most similar. Some of the regions of similarity could also be detected directly by searching a nucleic acid sequence database with the viral DNA sequences. The most extensive region of similarity was that which corresponded to the endonuclease in the pol gene of a murine leukemia virus. The majority of the rat-derived sequences present in the Harvey sarcoma virus genome can now be attributed exclusively to ras or retrovirus- or retrotransposon-related sequences.

Amino Acid Sequence↗
PubMed1987

Expression of an unusual isozyme of lactate dehydrogenase in the serum of cancer patients and comparison with carcinoembryonic antigen.

Two studies reported here demonstrate a statistically significant association between metastatic cancer and the appearance of the k isozyme of lactate dehydrogenase in serum of affected patients. The first study included 190 coded samples from three types of cancer patients and matched controls; the second included 155 preoperative and 200 postoperative colorectal cancer patients. In the second, plasma carcinoembryonic antigen was compared with serum k isozyme of lactate dehydrogenase as an indicator of the presence of metastatic cancer. This comparison showed that both markers were independently useful for assessing patient status and predicted that a combination of the two should be a better discriminator for the presence of metastases than either marker alone.

Biomarkers, Tumor↗
PubMed1987

Two-dimensional polyacrylamide gel electrophoresis analysis of phosphorylated, membrane-localized ras p21 proteins.

The ras p21 oncogene product migrates as a heterogeneous series of polypeptides as resolved by both one- and two-dimensional polyacrylamide gel electrophoresis (PAGE). We have prepared polyclonal rat serum antibody to ras p21 and used this as well as monoclonal antibodies to immunoprecipitate forms of p21 synthesized in vivo in transformed NIH3T3 cells. Two-dimensional PAGE of p21 resolved two distinct groups of polypeptides, one acidic (pI 4.8-5.3) which we call the "A" forms, and one less acidic or more basic (pI 6.5-7.0) which we call the "B" forms. It is the membrane-localized, B forms of v-ras-Ha p21 that are predominantly phosphorylated in vivo.

Animals↗
PubMed1987

In situ staining procedure for the detection of ornithine transcarbamylase activity in polyacrylamide gels.

Ornithine transcarbamylase deficiency is a human genetic disease potentially susceptible to gene therapy. A murine model system exists for the disease in the sparse-fur (spf) mouse. Before gene therapy studies can be performed it is necessary to have practical methods which could detect successful gene transfer. Therefore we have developed an in situ staining procedure for the detection of ornithine transcarbamylase activity in polyacrylamide gels. Following electrophoretic separation under nondenaturing conditions inorganic phosphate cleaved from carbamyl phosphate in gels as a result of enzymatic activity was precipitated as phosphomolybdic acid and visualized by reduction with ascorbic acid. Results from the procedure correlated with ornithine transcarbamylase activity as measured by solution assay for citrulline, the other product of the reaction. This procedure readily distinguished mutant forms of ornithine transcarbamylase as exemplified by the murine spf mutation and resolved ornithine transcarbamylases of all animals tested into multiple forms. The procedure further distinguished ornithine transcarbamylases of animals of several different genera while yielding virtually identical patterns of the enzyme from species within the same genus. This procedure also suggested that the human enzyme was more labile than murine ornithine transcarbamylase; direct thermolability studies confirmed this finding.

Animals↗
PubMed1987

Geographic and specialty distributions of WAMI Program participants and nonparticipants.

In an effort to make the geographic distribution of physicians closer to the distribution of the population as a whole, in 1971 the states of Washington, Alaska, Montana, and Idaho established the WAMI Program. In a departure from the Flexnerian model of medical education, the WAMI Program was organized to distribute the components of medical education throughout the region, both at the medical center at the University of Washington School of Medicine and at remote sites. In the present article, the authors describe the results of the first seven years of the program (1975-1981) in terms of the geographic and specialty distribution of the school's graduates before and after the establishment of the program. At the time of the study, 23 percent of the graduates with WAMI Program experience practiced in nonmetropolitan areas as defined by the U.S. Bureau of the Census. Only 13 percent of all U.S. physicians practiced in such areas in 1981, while 24 percent of the U.S. population lived there. In addition, 61 percent of the graduates with program experience were in primary care practice in contrast to 35 percent of all U.S. physicians. If all U.S. physicians behaved as these graduates do, the distribution of U.S. physicians would be reversed, with the proportion of physicians practicing primary care in nonmetropolitan areas being larger than the proportion of the population living in those areas.

Alaska↗
PubMed1985

LDHk in the retina of diverse vertebrate species: a possible link to the Warburg effect.

LDHk is a cancer-associated lactate dehydrogenase which is also found at high levels in normal mammalian retina. Such retinas share with most cancer tissues a dependence on aerobic glycolysis, leading to high production of lactate. However, retinas of lower vertebrate species are significantly less dependent on aerobic glycolysis. We find that retinas of species less dependent on aerobic glycolysis express significantly lower levels of an LDHk-like activity, less than or equal to the low levels seen in brains. The enzymes from lower species differ from the mammalian retinal enzyme in their pH optima and responsiveness to oxygen; but share a similar degree of inhibition by 5'-5'-dinucleoside tetraphosphates. Therefore, the expression pattern of LDHk in brain and retina of diverse vertebrate species suggests a link with the Warburg effect.

Adenine Nucleotides↗
PubMed1984

An unusual oxygen-sensitive lactate dehydrogenase isozyme associated with Kirsten murine sarcoma virus in human serum.

An unusual isozyme of lactate dehydrogenase, lactate dehydrogenase associated with Kirsten murine sarcoma virus (LDHk) was found in the sera of many patients with malignant tumors, while the sera of healthy persons had little or no such activity. This isozyme was detectable only when assayed in a nitrogen atmosphere, and its activity showed little or no relationship to the total lactate dehydrogenase activity as measured by a standard clinical assay. The activity of serum LDHk appeared to be correlated with the presence of known metastases. Increased serum LDHk appeared in a wide variety of patients with cancer, although it appeared to be more common in certain types of cancer. Increased serum LDHk activity was also found in the sera of some patients with nonmalignant disease. The activity of serum LDHk may be useful to monitor recurrence or response to therapy in certain types of cancer.

Adenine Nucleotides↗
PubMed1984

Fluctuation of a cancer-associated lactate dehydrogenase during S phase of the cell cycle in HeLa cells.

An unusual isozyme of lactate dehydrogenase, originally detected in Kirsten sarcoma virus-infected cells and later shown to be induced in normal mammalian cells by anaerobic shock, has also been reported at elevated levels in several human carcinomas. This enzyme is subject to inhibition by guanosine triphosphate and by the dinucleosides 5',5"'-diadenosine tetraphosphate and 5',5"'-diguanosine tetraphosphate (4). Fluctuation of the activity of this enzyme in soluble extracts of synchronized HeLa cells suggests the enzyme may be linked to DNA synthesis. The lactate dehydrogenase K activity increased in early S phase and then decreased to nearly undetectable levels during the period of most active DNA synthesis. This was observed in cells synchronized by thymidine excess or by aphidicolin, an inhibitor of DNA polymerase alpha.

Aphidicolin↗
PubMed1983

A cancer-associated lactate dehydrogenase is expressed in normal retina.

An unusual isozyme of lactate dehydrogenase, lactate dehydrogenase k, is found in high concentrations in cultured cells transformed by the Kirsten murine sarcoma virus and in many human cancer tissues. In experiments described here high levels of a lactate dehydrogenase k activity were detected in extracts of normal rodent retina. This activity had the same key properties as the human tumor isozyme, namely, a highly cathodic electrophoretic mobility and inhibition of enzymatic activity by oxygen and 5',5'-dipurinenucleoside tetraphosphates. Expression of this activity in the retina may be related to the high aerobic glycolysis characteristic of the retina, a metabolic feature shared with many tumors.

Animals↗
PubMed1983

Medicine vs. religion: the case of Jehovah's Witnesses.

When a Jehovah's Witness refuses to consent to needed medical treatment on religious grounds, a hospital's treatment team confronts a variety of ethical, legal, and medical dilemmas. This article explores the background and issues relating to cases in which Jehovah's Witnesses have refused treatment and discusses how the worker can effectively perform the tasks of case preparation, intervention, and advocacy with these clients.

Blood Transfusion↗
PubMed1983

Rapid test for detection of rabies antibodies in human serum.

A simple, sensitive, rapid method based on the principle of immunoadherence hemagglutination (IAHA) has been devised for the detection of rabies antibody. In this test, fixation of complement to complexes of rabies antigen with specific antibodies is readily detected by agglutination of human erythrocytes bearing receptors for C3. Sera from individuals undergoing preexposure rabies immunization were tested for rabies antibodies by the IAHA method and by a virus neutralization test performed in tissue culture, the rapid fluorescent focus inhibition test. IAHA titers showed a high degree of correlation with rapid fluorescent focus inhibition test titers, although it is not known whether results of the IAHA test represent the detection of neutralizing antibodies. An advantage of the IAHA test over the rapid fluorescent focus inhibition test was that results were obtained in a shorter period of time. In some instances, this can be of clinical significance in determining antibody levels to rabies virus. Furthermore, the IAHA test is most applicable as a rapid screening tool for the detection and quantitation of rabies antibodies in vaccinated subjects.

Antibodies, Viral↗
PubMed1982

Influence of age on accumulation of alpha-actin in satellite-cell-derived myotubes in vitro.

Because muscle satellite cells have been implicated in the process of muscle growth and mass regulation, as well as regeneration, alterations in the capacity of satellite cells to differentiate and accumulate muscle specific proteins during aging could play a role in the process of senile muscle atrophy. Skeletal muscle satellite cells were cultured from male rats from the following four age groups: neonatal rats (less than 5 days of age), growing rats (1--3 months of age, adult rats (9--12 months of age) and old rats (more than 24 months of age). A series of experiments was conducted in which cultures were harvested at daily intervals following fusion, and the amount of alpha-actin per myotube nucleus was determined. Analysis of maximum actin accumulation in myotubes from each experiment within each age group revealed no significant differences among cells derived from growing, adult or old rats; however, myotubes differentiating from neonatal muscle cells were able to accumulate more than three times as much alpha-actin per myotube nuclei as cells from the other three age groups. This result may reflect fundamental differences between authentic satellite cells and myogenic cells of prenatal origin. Aside from differences between neonatal cells and satellite cells, satellite cells from old muscle do not appear to have a diminished capacity to accumulate muscle-specific proteins following differentiation into muscle fibers.

Actins↗