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Biomedical subjects

C A Peterson

Publications and source records attributed to C A Peterson.

At least 19 recordsLinked to original sources
PubMed1995

Role of insulin-like growth factors and myogenin in the altered program of proliferation and differentiation in the NFB4 mutant muscle cell line.

In the present study we used the mutant muscle cell line NFB4 to study the balance between proliferation and myogenic differentiation. We show that removal of serum, which induced the parental C2C12 cells to withdraw from the cell cycle and differentiate, had little effect on NFB4 cells. Gene products characteristic of the proliferation state, such as c-Jun, continued to accumulate in the mutant cells in low serum, whereas those involved in differentiation, like myogenin, insulin-like growth factor II (IGF-II), and IGF-binding protein 5 (IGFBP-5) were undetectable. Moreover, NFB4 cells displayed a unique pattern of tyrosine phosphorylated proteins, especially in low serum, suggesting that the signal transduction pathway(s) that controls differentiation is not properly regulated in these cells. Treatment of NFB4 cells with exogenous IGF-I or IGF-II at concentrations shown to promote myogenic differentiation in wild-type cells resulted in activation of myogenin but not MyoD gene expression, secretion of IG-FBP-5, changes in tyrosine phosphorylation, and enhanced myogenic differentiation. Similarly, transfection of myogenin expression constructs also enhanced differentiation and resulted in activation of IGF-II expression, showing that myogenin and IGF-II cross-activate each other's expression. However, in both cases, the expression of Jun mRNA remained elevated, suggesting that IGFs and myogenin cannot overcome all aspects of the block to differentiation in NFB4 cells.

Animals↗
PubMed1995

Regulation of the myoblast-specific expression of the human beta-enolase gene.

The muscle-specific beta-enolase gene is expressed in proliferating adult myoblasts as well as in differentiated myotubes. Through deletion-transfection analysis, we identified a 79-base pair enhancer from the beta-enolase gene that leads to high level expression of a reporter gene in myoblasts, but not in fibroblasts. Following myoblast differentiation into myotubes, the activity of the enhancer declined, indicating that beta-enolase gene expression in myotubes is mediated by other regulators, possibly the myogenic helix-loop-helix family of transcription factors. Electrophoretic mobility shift assays indicated that proteins present in myoblast nuclear extracts specifically bind to the 3' half of the 79-base pair enhancer. This region contains an ets DNA-binding motif which is required not only for high level activity in myoblasts, but also for repressing activity in fibroblasts. Furthermore, the beta-enolase myoblast-specific enhancer shows limited similarity to the myoblast-specific enhancer associated with the human desmin gene, suggesting that gene expression in adult myoblasts may be coordinately regulated.

Animals↗
PubMed1995

Alterations in calcium intake on peak bone mass in the female rat.

This study compared the effect of a calcium deficit or surfeit on bone growth and development in the early phase of peak bone mass attainment with the late phase of peak bone mass attainment using the female Sprague-Dawley rat as a model. Groups of weanling animals were fed one of three nutritionally complete but calcium-altered diets (0.25%, 0.5%, or 1.0% calcium) for 8 weeks. Animals within each diet group were then rerandomized into one of the above diets and fed until 37 weeks of age. Each group contained five rats. In addition, three groups that received the 0.25% calcium diet for the first 8 weeks remained on the diet until week 20 when they were further randomized into one of the three diet groups and fed until 37 weeks of age. Results of this experiment indicate that increasing the calcium intake after adolescence (12-weeks-old) of those female rats consuming a low calcium diet will not substantially alter the adult bone volume of the metaphyseal region of the proximal tibia. Further, low calcium intakes through adolescence retard and prolong longitudinal bone growth. In contrast, however, those rats fed a diet providing calcium either at (0.5%) or twice the National Research Council's requirement level through adolescence had greater tibial bone volume as an adult when fed diets containing 1.0% calcium after this time period. It appears that the mechanism for this increase involves both a protection from resorption and an increase in bone formation/mineralization. This study is the first to show that low calcium intakes through adolescence have a nonreversible, deleterious effect on peak bone mass, whereas higher intakes promote greater peak bone mass and provide potential protection from age-related bone loss.

Analysis of Variance↗
PubMed1995

Assessment of blood pressure during naproxen therapy in hypertensive patients treated with nicardipine.

Nonsteroidal antiinflammatory drugs (NSAIDs) are known to attenuate the antihypertensive effects of a variety of antihypertensive agents including diuretics, beta-blockers, and vasodilators. Because of their unique mechanisms of actions, calcium channel blockers may not be subject to this interaction. This multicenter, double-blind, randomized, placebo-controlled study was designed to assess the effect of NSAID therapy on blood pressure control in stable hypertensive patients treated with a calcium channel blocker. One hundred patients with stable blood pressure control on 30 mg nicardipine three times a day were treated with 375 mg naproxen twice a day or placebo for 4 weeks. The mean diastolic blood pressures and estimated mean arterial pressures in both groups changed < 1 mm Hg during the 4 weeks of study drug treatment. None of the changes was significantly different from baseline and the two treatment groups were not significantly different from each other. Body weight in the placebo-treated patients did not change significantly whereas body weight in the naproxen-treated patients increased significantly, from 90.3 +/- 3.2 kg to 91.0 +/- 3.2 kg (mean = 0.7, P = .0003). At 4 weeks there was a mean loss of 0.1 kg in the placebo group and a mean gain of 0.4 kg in the naproxen group compared to baseline weights, neither of which was statistically significant (P = .60 and P = .071, respectively). These results indicate that despite a significant increase in body weight, the antihypertensive action of the calcium channel blocker nicardipine is not significantly affected by cotreatment with naproxen.

Adult↗
PubMed1995

Clinical results of the one-bone forearm.

Between 1973 and 1991, 19 patients underwent creation of a one-bone forearm at our institution as treatment for radioulnar instability secondary to trauma ("type 1" patients) or tumor resection or congenital deformity ("type 2" patients). Seventeen had failed previous reconstruction attempts. Ten one-bone forearms were constructed in neutral rotation, and nine in varying pronation (mean, 24 degrees). The distal ulna was absent or excised at the time of surgery in nine patients, partially excised in two, and shortened in one. At a mean follow-up interval of 42 months, the primary union rate was 68%, and the secondary rate was 74%. Using a rating scale devised for this study, 37% excellent, 32% good, 26% fair, and 5% poor results were noted. Poor results were statistically associated with previous trauma (type 1 patients), infection, severe nerve injury, and multiple previous surgical procedures. This is a retrospective study, and because of the limitations of such studies, no correlation of results with forearm rotational position, preoperative wrist or elbow dysfunction, fusion location, distal ulna excision or synostosis union was noted. Significant complications were noted in 10 patients, with a higher rate in type 1 patients. Although one-bone forearm construction remains a viable salvage option for forearm instability in selected patients, results may be less predictable than previously reported.

Adult↗
PubMed1995

Cell culture systems as tools for studying age-related changes in skeletal muscle.

Two aspects of muscle cell phenotype that may be affected by aging are amenable to study in vitro: proliferative potential and ability to differentiate. These processes in primary myoblast cultures as well as in established myoblast cell lines will be examined, and the usefulness of these in vitro systems in addressing fundamental molecular mechanisms of muscle aging will be discussed.

Adolescent↗
PubMed1995

An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair.

Replication protein A (RPA) is required for simian virus 40-directed DNA replication in vitro and for nucleotide excision repair (NER). Here we report that RPA and the human repair protein XPA specifically interact both in vitro and in vivo. Mapping of the RPA-interactive domains in XPA revealed that both of the largest subunits of RPA, RPA-70 and RPA-34, interact with XPA at distinct sites. A domain involved in mediating the interaction with RPA-70 was located between XPA residues 153 and 176. Deletion of highly conserved motifs within this region identified two mutants that were deficient in binding RPA in vitro and highly defective in NER both in vitro and in vivo. A second domain mediating the interaction with RPA-34 was identified within the first 58 residues in XPA. Deletion of this region, however, only moderately affects the complementing activity of XPA in vivo. Finally, the XPA-RPA complex is shown to have a greater affinity for damaged DNA than XPA alone. Taken together, these results indicate that the interaction between XPA and RPA is required for NER but that only the interaction with RPA-70 is essential.

Amino Acid Sequence↗
PubMed1995

Mutations in XPA that prevent association with ERCC1 are defective in nucleotide excision repair.

The human repair proteins XPA and ERCC1 have been shown to be absolutely required for the incision step of nucleotide excision repair, and recently we identified an interaction between these two proteins both in vivo and in vitro (L. Li, S. J. Elledge, C. A. Peterson, E. S. Bales, and R. J. Legerski, Proc. Natl. Acad. Sci. USA 91:5012-5016, 1994). In this report, we demonstrate the functional relevance of this interaction. The ERCC1-binding domain on XPA was previously mapped to a region containing two highly conserved XPA sequences, Gly-72 to Phe-75 and Glu-78 to Glu-84, which are termed the G and E motifs, respectively. Site-specific mutagenesis was used to independently delete these motifs and create two XPA mutants referred to as delta G and delta E. In vitro, the binding of ERCC1 to delta E was reduced by approximately 70%, and binding to delta G was undetectable; furthermore, both mutants failed to complement XPA cell extracts in an in vitro DNA repair synthesis assay. In vivo, the delta E mutant exhibited an intermediate level of complementation of XPA cells and the delta G mutant exhibited little or no complementation. In addition, the delta G mutant inhibited repair synthesis in wild-type cell extracts, indicating that it is a dominant negative mutant. The delta E and delta G mutations, however, did not affect preferential binding of XPA to damaged DNA. These results suggest that the association between XPA and ERCC1 is a required step in the nucleotide excision repair pathway and that the probable role of the interaction is to recruit the ERCC1 incision complex to the damage site. Finally, the affinity of the XPA-ERCC1 complex was found to increase as a function of salt concentration, indicating a hydrophobic interaction; the half-life of the complex was determined to be approximately 90 min.

Amino Acid Sequence↗
PubMed1995

Simultaneous treatment with IGF-I and GH additively increases anabolism in parenterally fed rats.

We compared the effects of recombinant human insulin-like growth factor I [rhIGF-I, 800 micrograms/day, coinfused with total parenteral nutrition (TPN)], growth hormone (rhGH, 800 micrograms/day, subcutaneous injection twice daily), and simultaneous treatment with rhIGF-I and rhGH (800 + 800 micrograms/day) in rats subjected to surgical stress and maintained with TPN. Weight gain induced by IGF-I plus GH was double that shown by IGF-I or GH alone. Although weight gain was similar with IGF-I or GH, IGF-I selectively increased heart, kidney, thymus, spleen, and small intestine mass, whereas GH selectively increased gastrocnemius muscle mass. IGF-I and/or GH increased carcass protein and water while decreasing fat. Serum total and free IGF-I levels were highest with IGF-I plus GH. Serum rat GH levels were reduced with IGF-I and/or GH. IGF-I given with GH reversed the GH-induced increase in serum insulin. In summary, IGF-I and GH show tissue-specific anabolic effects, and simultaneous treatment with IGF-I plus GH additively increases anabolism during TPN.

Animal Nutritional Physiological Phenomena↗
PubMed1994

Assignment of xeroderma pigmentosum group C (XPC) gene to chromosome 3p25.

The human gene XPC (formerly designated XPCC), which corrects the repair deficiency of xeroderma pigmentosum (XP) group C cells, was mapped to 3p25. A cDNA probe for Southern blot hybridization and diagnostic PCR analyses of hybrid clone panels informative for human chromosomes in general and portions of chromosome 3 in particular produced the initial results. Fluorescence in situ hybridization utilizing both a yeast artificial chromosome DNA containing the gene and XPC cDNA as probes provided verification and specific regional assignment. A conflicting assignment of XPC to chromosome 5 is discussed in light of inadequacies in the exclusive use of microcell-mediated chromosome transfer for gene mapping.

Animals↗
PubMed1992

Structure and lens expression of the gene encoding chicken beta A3/A1-crystallin.

The beta A1- and beta A3-crystallins are major polypeptides in the lenses of vertebrates. We present evidence that a single beta A3/A1 gene encodes these two proteins in the chicken. The beta A3/A1 gene has been sequenced and its functional promoter identified in transfection experiments. The chicken beta A3/A1 gene has the same structure as the human orthologue: six exons with standard splice sites and two alternative start codons from which the protein products are apparently translated. Northern analysis revealed an abundant 0.9-kb transcript in the lenses of 1-2-day-old chickens and no detectable transcripts in the rest of the eye, brain, heart, kidney, liver or skeletal muscle. The 5'-flanking sequence of the chicken beta A3/A1 gene is very similar to that of the human and mouse genes, suggesting conservation of important putative regulatory sequences in addition to the TATA box. A thymidine-rich element (bp -218 to -163) and a potential AP-1-binding site (bp -264 to -258) are present within the chicken 5'-flanking region. A DNA fragment from -382 to +22 of the chicken beta A3/A1 gene is sufficient to promote expression of the bacterial cat gene in transfected chicken primary lens epithelial cells, but not in transfected dermal fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Beta-enolase is a marker of human myoblast heterogeneity prior to differentiation.

In this report, we define a muscle-specific marker, beta-enolase, that distinguishes proliferating myoblasts from different stages of development. Enolase exists as multiple isoforms and in the course of cardiac and skeletal muscle development the beta isoform progressively replaces the alpha isoform. In skeletal muscle, this change in gene expression, unlike most developmental changes in myogenic gene expression, is evident in undifferentiated myoblasts. Whereas myoblasts from fetal tissues express alpha-enolase mRNA, beta-enolase is the predominant mRNA expressed by myoblasts from postnatal tissues. Our results are consistent with the idea that distinct precursor myoblasts contribute to the diversity of fiber types characteristic of muscle tissue at different stages of development.

Animals↗
PubMed1992

Bone composition and histology of young growing rats fed diets of varied calcium bioavailability: spinach, nonfat dry milk, or calcium carbonate added to casein.

Bone composition and histology were evaluated in young growing rats fed nutritionally complete but calcium-restricted (0.15%) diets in which calcium was derived from spinach, nonfat dry milk (NFDM), or CaCO3 added to casein. Groups of male weanling rats were pair-fed for 28 d. A 0.5% calcium casein-based diet group fed ad libitum was included to provide a comparison of normal bone structure and composition. Bone growth and bone ash were depressed in spinach-fed rats. Total bone tibia calcium in 0.5% calcium casein-based, 0.15% calcium casein-based, NFDM and spinach diet groups were 64.0, 29.2, 30.7 and 13.8 mg, respectively. All other measured bone mineral levels were also lower, except for potassium. Femur hydroxyproline concentrations were 1.2, 1.6, 1.6 and 2.1% in 0.5% calcium casein-based, 0.15% calcium caseinbased, NFDM and spinach diet groups, respectively. Bone histomorphometry indicated gross underdevelopment and compromised mineralization of trabecular bone of spinach-fed rats. For the first time, it has been demonstrated with histologic techniques that calcium from the low bioavailable source, spinach, compromises both the quantity and quality of bone. In contrast, when calcium is fed to growing animals at levels below the National Research Council requirement but from a highly bioavailable source (i.e., NFDM and CaCO3), there is only a reduction in bone quantity.

Animals↗
PubMed1992

A psychotic gynemimetic: I just had a pregnant thought.

Nomothetic and idiographic content analytic approaches to the Rorschach are used in complementary fashion to explore the psychotic personality structure and primitive interpersonal models in a 37-year-old biologically normal male, who was a gynemimetic, that is, a transvestite who aspired to have the genetalia of a woman. The Rorschach was riddled with psychotic verbalizations and imagery suggesting inadequate differentiation from the original symbiosis, inadequate symbiosis anxiety, and significant separation anxiety--a constellation culminating in the transsexual fantasy of fusion with the mother.

Adult↗
PubMed1992

Aloneness and the Isakower phenomenon.

Under the sway of the oedipal imperative, the Isakower phenomenon has long been regarded as a regressive perceptual defense against castration anxiety accompanying incestuous wishes, often stimulated by primal scene exposure-fantasy. Clinical material from the psychoanalytic psychotherapy of a borderline patient with object constancy deficits is offered to support a reconceptualization of the Isakower phenomenon: Following annihilatory rage and the destruction of extant inner objects, resulting in a regression to the "drive organization of memory," the face-breast imagery within the Isakower phenomenon arrives as a hallucinatory alternative to unbearable aloneness.

Anxiety, Separation↗
PubMed1991

A rapid method for macerating phloem.

Sieve cells and sieve tube members can be macerated from the phloem of various organs of woody and herbaceous species by autoclaving the tissue in a mild macerating medium. This treatment does not digest the primary walls or the callose deposits on the sieve areas and sieve plates of the sieve elements. These cells can then be recognized by the fluorescence of their callose after staining with aniline blue. Sometimes adjacent sieve elements fail to separate and one can observe details of their junctures.

Cytological Techniques↗