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Biomedical subjects

R E Thayer

Publications and source records attributed to R E Thayer.

At least 19 recordsLinked to original sources
PubMed2006

Altered metabolism and mitochondrial genome in prostate cancer.

Mutations in mitochondrial DNA are frequent in cancer and the accompanying mitochondrial dysfunction and altered intermediary metabolism might contribute to, or signal, tumour pathogenesis. The metabolism of human prostate peripheral zone glandular epithelial cells is unique. Compared with many other soft tissues, these glandular epithelial cells accumulate high concentrations of zinc, which inhibits the activity of m-aconitase, an enzyme involved in citrate metabolism through Krebs cycle. This causes Krebs cycle truncation and accumulation of high concentrations of citrate to be secreted in prostatic fluid. The accumulation of zinc also inhibits terminal oxidation. Therefore, these cells exhibit inefficient energy production. In contrast, malignant transformation of the prostate is associated with an early metabolic switch, leading to decreased zinc accumulation and increased citrate oxidation. The efficient energy production in these transformed cells implies increased electron transport chain activity, increased oxygen consumption, and perhaps, excess reactive oxygen species (ROS) production compared with normal prostate epithelial cells. Because ROS have deleterious effects on DNA, proteins, and lipids, the altered intermediary metabolism may be linked with ROS production and accelerated mitochondrial DNA mutations in prostate cancer.

DNA, Mitochondrial↗
PubMed2000

The efficacy of SPORT as a dietary supplement on performance and recovery in trained athletes.

This study investigated the efficacy of SPORT (a popular dietary supplement) in improving performance and assisting recovery in 9 trained athletes. In a double-blind, crossover experiment, subjects ran at workloads of 60 and 80% of peak oxygen uptake (Peak VO2) for 5 min each with 5 min recovery after each bout and at 100% Peak VO2 until exhaustion. Two capsules of either SPORT or a gelatin placebo were administered 1 hr prior to exercise and immediately after each workload. Heart rate (HR) and blood lactate (BLa) were measured at 1 hr prior to exercise, immediately after the 100% exercise bout and at 5, 10, 20, and 45 min during recovery. No significant differences between treatments on HR and BLa measures at any of the 6 time periods, or on subjects' time to exhaustion were found. Under the conditions of this experimental design, SPORT had no beneficial effects on performance or recovery in trained athletes.

Adult↗
PubMed1999

Changes in rat muscle with compensatory overload occur in a sequential manner.

The present study was initiated to determine the time course of changes in the profile of selected skeletal muscle myofibril proteins during compensatory overload. Whole muscle isometric contractile properties were measured to assess the physiological consequences of the overload stimulus. Compensatory overload of plantaris muscle of rats was induced by surgical ablation of the synergistic soleus and gastrocnemius muscles. Myosin light chain (LC) and tropomyosin (TM) compositions of control (CP) and overloaded plantaris (OP) muscles were determined by electrophoresis and myofibrillar ATPase assays were performed to assess changes in contractile protein interactions. Within one week of overload decreases in the alpha:beta TM ratio and myofibrillar ATPase activity were observed. Following 30 days of overload, a transition in type II to type I fibres was associated with an increase in slow myosin LC1. Interestingly, after 77 days of overload, the TM subunit ratio returned to one resembling a fast twitch muscle. It is proposed that the early and transitory changes in the TM subunits of OP, as well as the rapid initial depression in maximum tetanic isometric force and myofibrillar ATPase activity may be explained as a result of muscle fibre degeneration-regeneration. We propose that alterations in protein expression induced by compensatory overload reflect both degenerative-regenerative change and increased neuromuscular activity.

Adaptation, Physiological↗
PubMed1994

Self-regulation of mood: strategies for changing a bad mood, raising energy, and reducing tension.

Four studies evaluated the success of behaviors and strategies used to self-regulate bad moods, raise energy, and reduce tension. Study 1 (N = 102) used an open-ended questionnaire to identify behavioral categories. Studies 2 and 4 surveyed a representative sample (N = 308) with a fixed-response questionnaire to quantify behaviors, general strategies, and individual differences. Study 3 used psychotherapist (N = 26) judgments of the likely success of the strategies. Therapist and self-rating converged on success of strategies and gender differences. These studies clarify and confirm previous research findings, particularly gender differences in controlling depression. Exercise appears to be the most effective mood-regulating behavior, and the best general strategy to change a bad mood is a combination of relaxation, stress management, cognitive, and exercise techniques. Results support a 2-dimensional biopsychological model of mood.

Adolescent↗
PubMed1994

Acute and chronic response of skeletal muscle to resistance exercise.

Skeletal muscle tissue is sensitive to the acute and chronic stresses associated with resistance training. These responses are influenced by the structure of resistance activity (i.e. frequency, load and recovery) as well as the training history of the individuals involved. There are histochemical and biochemical data which suggest that resistance training alters the expression of myosin heavy chains (MHCs). Specifically, chronic exposure to bodybuilding and power lifting type activity produces shifts towards the MHC I and IIb isoforms, respectively. However, it is not yet clear which training parameters trigger these differential expressions of MHC isoforms. Interestingly, many programmes undertaken by athletes appear to cause a shift towards the MHC I isoform. Increments in the cross-sectional area of muscle after resistance training can be primarily attributed to fibre hypertrophy. However, there may be an upper limit to this hypertrophy. Furthermore, significant fibre hypertrophy appears to follow the sequence of fast twitch fibre hypertrophy preceding slow twitch fibre hypertrophy. Whilst some indirect measures of fibre number in living humans suggest that there is no interindividual variation, postmortem evidence suggests that there is. There are also animal data arising from investigations using resistance training protocols which suggest that chronic exercise can increase fibre number. Furthermore, satellite cell activity has been linked to myotube formation in the human. However, other animal models (i.e. compensatory hypertrophy) do not support the notion of fibre hyperplasia. Even if hyperplasia does occur, its effect on the cross-sectional area of muscle appears to be small. Phosphagen and glycogen metabolism, whilst important during resistance activity appear not to normally limit the performance of resistance activity. Phosphagen and related enzyme adaptations are affected by the type, structure and duration of resistance training. Whilst endogenous glycogen reserves may be increased with prolonged training, typical isotonic training for less than 6 months does not seem to increase glycolytic enzyme activity. Lipid metabolism may be of some significance in bodybuilding type activity. Thus, not surprisingly, oxidative enzyme adaptations appear to be affected by the structure and perhaps the modality of resistance training. The dilution of mitochondrial volume and endogenous lipid densities appears mainly because of fibre hypertrophy.

Exercise↗
PubMed1993

LINE-1: a human transposable element.

Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb segments that are active retrotransposons. Expression of these retrotransposons appears to be favored in cells of germ line origin, as well as in some other tumor cells of epithelial origin. In such cells, the product of the first L1Hs open reading frame (ORF), a protein called p40, is detectable; p40 has no apparent similarity to gag proteins, but contains a leucine zipper region which may be responsible for the occurrence of p40 multimers. Transcription of L1Hs initiates at residue 1 although the transcriptional regulatory regions are downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1-binding site in the first 20 bp reduces transcription by fivefold. Translation of the second ORF, which encodes reverse transcriptase, is independent of the translation of the frame encoding p40.

Amino Acid Sequence↗
PubMed1993

Undermethylation of specific LINE-1 sequences in human cells producing a LINE-1-encoded protein.

Nucleotide sequences near the 5' ends of some long interspersed elements-1 (LINE-1) from Homo sapiens (L1Hs) are undermethylated in cell lines which produce a L1Hs-encoded protein. In contrast, these sequences are methylated in cell lines with little or no detectable L1Hs expression. The fact that the 5' end of L1Hs is differentially methylated in cells exhibiting different levels of L1Hs expression suggests that the methylation state of this region plays a role in L1Hs expression.

Blotting, Southern↗
PubMed1993

Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory sequence in the human LINE-1 transposable element.

The first step of the currently favored model for the mechanism of transposition of the human LINE-1 element involves the synthesis of full length LINE-1 mRNA. Previous work demonstrated that the 5'-terminal 100 base pairs of the human LINE-1 element (L1Hs) has an important role in regulating it's expression. Here we report further deletion analysis revealing the presence of a cis regulatory element overlapping the region between base pairs +12 and +18. Oligonucleotides containing this sequence form a specific complex with a nuclear protein extracted from NTera2D1 and Jurkat cells, and with recombinant YY1 produced in E. coli. The complex is competed by YY1 binding sites found in other genes, and is ablated by anti-YY1 serum. These results suggest that YY1 is involved in the regulation of L1Hs transcription and therefore transposition.

Base Sequence↗
PubMed1990

Translation of LINE-1 DNA elements in vitro and in human cells.

The LINE-1 (L1) family of interspersed DNA sequences found throughout the human genome (L1 Homo sapiens, L1Hs) includes active transposable elements. Current models for the mechanism of transposition involve reverse transcription of an RNA intermediate and utilization of element-encoded proteins. We report that an antiserum against the polypeptide encoded by the L1Hs 5' open reading frame (ORF1) detects, in human cells, an endogenous ORF1 protein as well as the ORF1 product of an appropriate transfecting recombinant vector. The endogenous polypeptide is most abundant in teratocarcinoma and choriocarcinoma cells, among those cell lines tested; it appears to be a single species of approximately 38 kDa. In contrast, RNAs synthesized in vitro from cDNAs representing full-length, polyadenylylated cytoplasmic L1Hs RNA yield, upon in vitro translation, ORF1 products of slightly different sizes. This is consistent with the fact that the various cDNAs are different and represent transcription of different genomic L1Hs elements. In vitro studies additionally suggest that translation of ORF1 is initiated at the first AUG codon. Finally, in no case was an ORF1-ORF2 fusion protein detected.

Animals↗
PubMed1987

Genomic organization of low copy number sequences that are associated with deca-satellite DNA in the monkey genome.

A previously described segment of African green monkey DNA (cloned in phage lambda MkA) contains deca-satellite linked to DNA sequences that are estimated to occur once per genome. Sequences homologous to the low copy number sequences in lambda MkA are also associated with species-specific satellite DNAs in the human and mouse genomes. A second clone, lambda Mk8, contains a monkey DNA region that is colinear and homologous to a portion of the low copy number sequences in lambda MkA, but no satellite sequences. The two cloned segments are markedly different starting at a point proximal to the satellite DNA region in lambda MkA. DNA-blotting experiments indicate that lambda Mk8 but not lambda MkA represents the typical genomic organization and that the low copy number segments occur only once per haploid genome. The data suggest that rearrangements such as deletions or inversions occurring in monkey cells account in part for the structure of lambda MkA. Additional rearrangements may have occurred during cloning in E. coli. This unique chromosomal region may be particularly susceptible to recombination.

Animals↗
PubMed1987

Energy, tiredness, and tension effects of a sugar snack versus moderate exercise.

After either eating a candy bar or walking briskly for 10 min on 12 selected days, 18 volunteers made systematic self-ratings of their energy, tiredness, and tension feelings for a fixed 2-hr period each day in the context of their normal daily activities. The snacking or walking activity was randomly selected on each test day after completion of a pretest. Results indicated that walking was associated with higher self-rated energy and lower tension significantly more than was snacking. In the walk condition reliable increases in energy and decreases in tension were observed for 2 hr. The sugar snack condition was associated with significantly higher tension after 1 hr, and a pattern of initially increased energy and reduced tiredness, followed 1 hr later by increased tiredness and reduced energy. The results partially support a general conceptual hypothesis that sugar snacking is often motivated by a low-awareness attempt to raise energy. Additionally, the results clarify an apparent conflict between neurochemical research, which indicates that sugar ingestion increases the tendency to sleep, and popular nutrition theory, which indicates that it increases tension.

Adult↗
PubMed1986

Isolation of low-copy-number sequences that neighbor satellite DNA in mammals.

To investigate the role of satellite DNA in eukaryotic genomes, we isolated from an African green monkey (Cercopithecus aethiops) genomic library cloned segments containing the previously described deca-satellite linked to low-copy-number genomic sequences. Three such clones were obtained. The low-copy-number sequences in the three clones do not cross-hybridize suggesting that they derive from different genomic loci. The structure of one of the clones, lambda MkA, is described in detail. Subcloned segments containing the low-copy-number sequences from lambda MkA anneal to monkey, human and mouse genomic DNA. The subcloned probes were used to select clones containing homologous sequences from a second, independent monkey library as well as from human and mouse genomic libraries. Several of the newly isolated monkey clones hybridized to probes containing the species-specific deca- and alpha-satellites, confirming the genomic association of the low-copy-number sequence in lambda MkA with satellite DNA. Moreover, several of the human and mouse clones hybridized to species-specific human and mouse satellite DNAs, respectively. These experiments indicate that the low-copy-number sequence in lambda MkA and its association with satellite DNA is conserved in primates and rodents.

Animals↗
PubMed1983

Homology between the KpnI primate and BamH1 (M1F-1) rodent families of long interspersed repeated sequences.

The KpnI and BamH1 (or M1F-1) families are the predominant sets of long interspersed repeated DNA sequences (LINEs) in primates and rodents, respectively. Recently, the sequences of several cloned subsegments from each family were determined in different laboratories. These sequences have now been compared and found to be homologous over at least 1400 bp. The data suggest that the two LINE families had a common progenitor and have been conserved in similar abundance although in divergent forms in the two mammalian orders.

Animals↗
PubMed1983

Kpn I family of long interspersed repeated DNA sequences in primates: polymorphism of family members and evidence for transcription.

An approximately equal to 2-kilobase-pair-long member (Kpn I-LS1) of the African green monkey Kpn I family of repeated sequences has been cloned, subjected to sequence analysis, and compared to other family members which are over 6 kilobase pairs (Kpn I-alpha 7) and 829 base pairs (Kpn I-RET) long. Both Kpn I-LS1 and Kpn I-RET lack sequences found at the ends of the longer family member and their structures resemble those of processed genes. Kpm I-LS1 sequences are colinear with part of the long family member, Kpn I-alpha 7. However, although all sequences in Kpn I-RET are represented in Kpn I-LS1, the two are not colinear; Kpn I-RET is missing 731 base pairs found in Kpn I-LS1 and one segment flanking the deletion is inverted. The results demonstrate that Kpn I family members are not only of different lengths but may also contain scrambled arrangements of common sequences. Sequences in Kpn I-LS1 hybridize to RNA from monkey and human cells, indicating that some family members are transcribed.

Animals↗
PubMed1983

Interruption of an alpha-satellite array by a short member of the KpnI family of interspersed, highly repeated monkey DNA sequences.

We describe here the interruption of a cloned African green monkey alpha-satellite array by an 829-base-pair-long nonsatellite DNA segment. Hybridization experiments indicate that the sequences within the interruption are homologous to segments frequently found in the 6-kilobase-pair-long members of the KpnI family of long, interspersed repeats. These data confirm and extend earlier results suggesting that sequences common to the KpnI family can occur independently of one another and in segments of variable lengths. The 829-base-pair-long segment, which is termed KpnI-RET, contains a terminal stretch of adenosine residues preceded by two typical but overlapping polyadenylation sites. KpnI-RET is flanked by direct repeats of a 14-base-pair-long segment of alpha-satellite that occurs only once in the satellite consensus sequence. These structural features suggest that KpnI-RET was inserted into the satellite array as a movable element.

Animals↗
PubMed1981

Sequence relationships between single repeat units of highly reiterated African Green monkey DNA.

Individual monomer and dimer units of the highly repeated alpha-component DNA of African Green monkeys were isolated and amplified by molecular cloning in pBR322. The purified sequences were characterized by digestion with restriction endonucleases and by primary nucleotide sequence analysis. Comparison of the cloned units with the 172 base pair long sequence representing the most abundant nucleotide at each position in the set of sequences comprising alpha-component allows the following conclusions. The set of sequences comprising alpha-component is made up of a very large number of related but slightly divergent sequences. Two neighboring repeats of the monomer unit are not necessarily more similar to one another than are randomly isolated monomers.

Animals↗