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Biomedical subjects

C C Nelson

Publications and source records attributed to C C Nelson.

At least 19 recordsLinked to original sources
PubMed1998

Axon withdrawal during synapse elimination at the neuromuscular junction is accompanied by disassembly of the postsynaptic specialization and withdrawal of Schwann cell processes.

Nerve terminal withdrawal is accompanied by a loss of acetylcholine receptors (AChRs) at corresponding postsynaptic sites during the process of synapse elimination at developing () and reinnervated adult () neuromuscular junctions. Aside from AChR and nerve terminal loss, however, the molecular and cellular alterations that occur at sites of elimination are unknown. To gain a better understanding of the cascade of events that leads to the disassembly of synaptic sites during the synapse elimination process, we surveyed the distribution of molecular elements of the postsynaptic specialization, the basal lamina, and supporting Schwann cells during the process of synapse elimination that occurs after reinnervation. In addition, quantitative techniques were used to determine the temporal order of disappearance of molecules that were lost relative to the loss of postsynaptic AChRs. We found that the dismantling of the postsynaptic specialization was inhomogeneous, with evidence of rapid dissolution of some aspects of the postsynaptic apparatus and slower loss of others. We also observed a loss of Schwann cell processes from sites of synapse elimination, with a time course similar to that seen for nerve terminal retraction. In contrast, all of the extracellular markers that we examined were lost slowly from sites of synapse loss. We therefore conclude that the synapse elimination process is synapse-wide, removing not only nerve terminals but also Schwann cells and many aspects of the postsynaptic apparatus. The disassembly occurs in a stereotyped sequence with some synaptic elements appearing much more stable than others.

Animals↗
PubMed1997

Controlling for general and disease-specific effects in child and family adjustment to chronic childhood illness.

Investigated the differential associations of asthma and diabetes on children's self-competence, family functioning, and maternal coping. Interactions of gender with the presence of chronic childhood illness were also assessed. Seventy-two children with diabetes and 40 children with asthma participated as subjects. Mothers completed measures of family functioning, coping, and disease severity while children completed Harter's (1985) Self-Perception Profile for Children. Results indicated that gender and type of chronic illness were independently associated with children's self-competence and family functioning but not maternal coping. However, differences attributable to specific illnesses dissipated once general family factors and general chronic childhood illness variables were controlled statistically. Differences based on child gender remained robust. Results are discussed within the context of categorical and noncategorical approaches to the study of chronic childhood illness.

Adaptation, Psychological↗
PubMed1997

Recurrent trichofolliculoma of the upper eyelid margin.

We report a woman who had a recurrent trichofolliculoma on the upper eyelid margin. Only three cases of this benign tumor on the eyelid have been reported, and no recurrence in this location had been noted in the literature. The lesion, present for 6 years, had been excised twice previously (3 and 4 years before), recurred, and had been injected with a steroid preparation 2 years earlier. Lashes, both normal-looking and immature, arose from the center area of this lesion, and telangiectatic vessels were on its surface. Full-thickness wedge resection was used to excise the lesion completely. Complete primary excision of trichofolliculoma is important, and local steroid preparations should not be used.

Adult↗
PubMed1996

Retinoid X receptor alters the determination of DNA binding specificity by the P-box amino acids of the thyroid hormone receptor.

Nuclear hormone receptors bind to hormone response elements in DNA consisting of two half-sites of 6 base pairs. The P-box amino acids of each receptor determine the identities of the central nucleotides of the half-site. 57 P-box variants of the human thyroid hormone receptor (hT3Rbeta) were used to demonstrate the relationship between P-box sequence and DNA binding specificity by homodimers and heterodimers formed with the retinoid X receptor (RXR). In general, the formation of heterodimers relieved many of the constraints on the compatibility of hT3Rbeta P-box sequences with DNA binding. Effects were most dramatic for heterodimers bound to a direct repeat spaced by four base pairs. RXR also overrides the P-box-derived DNA binding specificity of hT3Rbeta when heterodimers are bound to inverted or everted repeat elements. These effects of RXR are most pronounced on AGGTCA half-sites but are squelched when the RXR partner of the heterodimer is bound to an AGGACA half-site. The influence of RXR on hT3Rbeta DNA binding specificity varies with the orientation of half-sites in the element, the identity of the fourth base pair of the half-site, and the spacing between the half-sites of direct repeats. These differences suggest that the DNA binding domains of RXR-hT3Rbeta heterodimers are not positioned equivalently on the various elements, affecting the manner in which the P-box amino acids of hT3Rbeta interact with base pairs within the half-site.

Amino Acid Sequence↗
PubMed1995

Relationship between P-box amino acid sequence and DNA binding specificity of the thyroid hormone receptor. The effects of half-site sequence in everted repeats.

The three P-box amino acids in the DNA recognition alpha-helix of steroid/thyroid hormone receptors participate in the discrimination of the central base pairs of the hexameric half-sites of receptor response elements in DNA. A series of 57 variants of the beta isoform of the human thyroid hormone receptor were constructed in which the 19 possible amino acid substitutions were incorporated at each of the three P-box positions. The effects of these substitutions on the sequence specificity of the DNA binding activity of the receptor were analyzed using 16 everted repeat elements which differed in sequence in the two central base pairs of the hexameric half-sites. Only receptors with glutamate or aspartate as the first P-box amino acid had detectable DNA binding affinity on everted repeats with AGGNCA half-sites. Only those receptors with alanine, glycine, serine, or proline in the second P-box position were able to bind to this same group of everted repeat elements. In contrast, many of the variant receptors with substitutions at the third P-box position were capable of binding to the AGGNCA group of repeat elements. The actual substitutions at the third P-box position that were compatible with binding depended upon the identity of the fourth base pair of the AGGNCA half-sites. Of the remaining 12 everted repeat sequences, only those with AGTTCA or AGTCCA half-sites were able to bind any of the receptors. In addition to wild type receptor, several variant receptors with amino acid substitutions in either the first or third P-box position were able to bind to the everted repeat with AGTTCA half-sites. The everted repeat with AGTCCA half-sites was bound by receptors with a DGG, NGG, or EGQ P-box sequence, but not the wild type receptor which has an EGG P-box sequence. These data demonstrate that all three P-box positions of the thyroid hormone receptor function to discriminate between half-sites that differ in sequence at the third and fourth base pairs.

Amino Acid Sequence↗
PubMed1995

Relationship between P-box amino acid sequence and DNA binding specificity of the thyroid hormone receptor. The effects of sequences flanking half-sites in thyroid hormone response elements.

The three P-box amino acids in the DNA recognition alpha-helix of steroid/thyroid hormone receptors participate in the discrimination of the central base pairs of the hexameric half-sites of receptor response elements in DNA. Using a series of variant receptors incorporating all 19 possible substitutions for each individual P-box amino acid of the human thyroid hormone receptor (hT3R beta), we demonstrated that the first P-box position must have a glutamate, and the second P-box position must have either an alanine or a glycine for high affinity binding to everted repeat elements with half-site sequences of AGGNCA. In the present study, the influence of half-site flanking sequence on the compatibility of P-box amino acids in hT3R beta with DNA binding was investigated. When a 5' sequence of CTG flanked AGGNCA half-sites in an everted repeat, several additional P-box variant receptors were able to bind to the DNA that were not able to bind when the half-sites were flanked with the 5' sequence CAG. Flanking sequence had the most dramatic effects on amino acid substitutions at the first P-box position, with smaller effects observed at the second P-box position and only subtle effects observed at the third P-box position. Expansion of the number of P-box sequences compatible with binding of hT3R beta to thyroid hormone response elements required the thymidine in the CTG flanking sequence, an everted repeat of the AGGNCA half-sites, and an intermolecular interaction in the C terminus of the receptor.

Amino Acid Sequence↗
PubMed1995

Constitutive transactivation by the thyroid hormone receptor and a novel pattern of activity of its oncogenic homolog v-ErbA in Xenopus oocytes.

In Xenopus oocytes, the rat thyroid hormone receptor alpha (rTR alpha), but not its oncogenic homolog v-ErbA, constitutively activated thyroid hormone (T3)-responsive reporter genes at four positive thyroid hormone-responsive elements (TREs). At a subset of the positive TREs tested, the addition of T3 resulted in a further enhancement of reporter gene activation. In contrast, both rTR alpha and v-ErbA functioned as constitutive activators when bound to the clone 122 TREs, which are induced by unliganded TR in mammalian cells. Therefore, the responses of the ligand-independent activation domains of TR and v-ErbA to cell-specific and TRE-mediated induction are not equivalent. Coexpression of the human retinoid X receptor alpha (hRXR alpha) enhanced both ligand-dependent and ligand-independent activation functions of rTR alpha and human TR beta (hTR beta) at a palindromic TRE (TREp). An endogenous TR activity mediated T3 induction of TREp, while being repressed by an in vitro-generated dominant negative mutant of TR. T3-mediated gene activation, by exogenous or endogenous TR, was repressed by v-ErbA at three positive TREs, but not at the TRE from the third intron of the rat GH gene (rGH3 TRE). Interestingly, preinjection of nuclear protein extract from anterior pituitary cells converted v-ErbA into a constitutive activator at rGH3 TRE. The pituitary-specific factor Pit-1/GHF-1 or hRXR alpha did not induce activation by v-ErbA at rGH3 TRE, suggesting that the dominant negative phenotype of v-ErbA can be abolished by direct or indirect interactions with other nuclear factors.

Animals↗
PubMed1994

Measurements of upper eyelid and eyebrow dimensions in healthy white individuals.

Facial appearance is influenced by the anatomic relationship of the eyebrow and eyelid, and surgical procedures on these structures attempt to restore or preserve not only symmetry but also normal appearance. To provide useful benchmarks for such interventions, we measured the eyebrow height, upper eyelid crease height, and amount of visible pretarsal skin of 143 white subjects who had no facial abnormalities. An age effect was observed for all measures, indicating a direct relationship with age until the middle age range (41 to 60 years), when mean estimates leveled off or decreased somewhat relative to younger age groups. Within the 41- to 60-year age group, for example, the average (S.D.) values for pretarsal skin height, eyelid crease height, and eyebrow height were 1.4 mm (1.1 mm), 6.4 mm (1.2 mm), and 6.4 mm (1.8 mm), respectively. Eyebrow and pretarsal skin heights were greater in females than males, and eyelid crease height showed similar gender-related trends. With increasing age, variation around the mean estimates for eyelid and eyebrow measurement increased, which may be indicative of variability across individuals in the physiologic response to the aging process. As expected, a high degree of intereye correlation was observed (correlation coefficients of 0.87 to 0.96). These results emphasize the importance of providing a normal anatomic relationship that relates to the patient's age and gender, as well as an outcome that is symmetric, in corrective or cosmetic procedures on the eyelid and eyebrow.

Adolescent↗
PubMed1994

Drill guide for hydroxyapatite implants.

A drill guide to facilitate the second drilling of hydroxyapatite orbital implants is presented. The drill guide is adaptable to various drill types. It is nontraumatic and provides excellent, one-handed fixation, eliminating the need for an assistant. It allows for consistent, straight drilling to a predetermined depth and, because it is encased, it protects the patient from injury. The drill guide has been used on 30 patients and is without untoward effects.

Durapatite↗
PubMed1994

Effects of maternal hospitalization in early childhood: anticipated anxiety associated with an analog separation for childbirth and surgery.

Assessed early childhood anticipation of anxiety in response to analog 3-day maternal hospitalization for surgery or childbirth. Reaction to analog nonhospital separation was also assessed. Within each condition, gender effects were examined. Participants were 120 first-grade children at four elementary schools. Between-groups comparisons showed maternal separation for surgery was anticipated as more anxiety provoking, whereas anxiety associated with separation for childbirth and nonhospital separation was anticipated as similar. In general, within each separation situation, girls and boys anticipated similar levels of anxiety.

Anxiety, Separation↗
PubMed1994

The effects of P-box substitutions in thyroid hormone receptor on DNA binding specificity.

Three "P-box" amino acids within the DNA recognition alpha-helix of members of the steroid hormone and thyroid hormone families of nuclear receptors are known to determine the identity of two of the six base pairs within the half-sites of cognate DNA elements. We introduced P-box substitutions derived from different members of the thyroid hormone/estrogen receptor (T3R/ER) family into the beta-isoform of human thyroid hormone receptor (hT3R beta) and tested the DNA binding and transactivation activities of these mutants using thyroid hormone response elements (TREs) with half-sites composed of different sequences and arranged in different orientations. Different P-box sequences derived from the T3R/ER family resulted in distinct DNA binding specificities determined by the fourth base pair of the half-site. Thyroid hormone receptor mutants containing EGA, EAA, EGS substitutions for the wild type EGG P-box bound with wild type affinity to consensus AGGTCA half-sites, regardless of orientation. TREs composed of AGGACA half-sites bound hT3R beta s with an EGG or EAA P-box sequence, but not those with EGA or EGS P-box sequence. A reversal of this specificity was observed on a direct repeat TRE with AGGGCA half-sites. Additionally, an ESG P-box substitution in hT3R beta prevented the receptor from binding to a direct repeat as a homodimer, but this mutant could bind as a heterodimer with retinoid X receptor or to the everted repeat TRE from the chicken lysozyme promoter.

Amino Acid Sequence↗
PubMed1993

Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions.

We have studied the spatial deployment of synapses arising from different axons that converge on the same developing neuromuscular junctions. Labeling the competing synaptic "cartels" with different dyes in mouse muscle showed that, perinatally, each axon adds similar terminal areas, whereas later, areas occupied by the competing cartels diverged by gradual elimination of one axon's synapses and ongoing addition of synaptic area by the other. Activity-dependent labeling of synapses capable of vesicle recycling in snake muscle also revealed a gradual change in territories occupied by competing inputs, implying that an axon maintained some functional synapses even as others in its cartel were being eliminated. Thus the process of synapse elimination is gradual, with loss of one viable synapse after another, until an axon is left with no synaptic territory and withdraws.

Animals↗
PubMed1993

Gas chromatography/tandem mass spectrometry measurement of delta 9-tetrahydrocannabinol, naltrexone, and their active metabolites in plasma.

The combination of gas chromatography and mass spectrometry (GC/MS) is generally recognized as offering the best sensitivity and specificity for the detection and measurement of drugs and their metabolites in biological specimens. This finding has resulted in the widespread use of GC/MS in many areas of pharmacology and toxicology. However, a GC/MS assay can be performed in many ways, depending upon the specific requirements of the analytical tasks. For example, pharmacokinetic studies generally employ chemical ionization and single-ion monitoring to obtain optimum sensitivity, whereas GC/MS methods for confirmation of the presence of drugs of abuse in urine most often use electron ionization and multiple-ion monitoring to obtain conclusive results. Another example is the increasing use of the combination of gas chromatography and tandem mass spectrometry (GC/MS/MS) for analyses requiring sensitivities better than nanograms per milliliter. Examples of the application of GC/MS and GC/MS/MS methods for the detection of delta 9-tetrahydrocannabinol, naltrexone, and their active metabolites are described and compared in terms of sensitivity, specificity, and unique features.

Dronabinol↗
PubMed1993

Tissue specificity and serologic reactivity of an autoantigen associated with autoimmune thyroid disease.

A recent report has identified a new autoantigen called D1 that appears to be associated with Graves' ophthalmopathy and is expressed in the thyroid and eye muscle. To better characterize the tissue specificity and disease relevance of this antigen, we evaluated the expression of D1 RNA in various human tissues using a reverse transcriptase polymerase chain reaction assay. These studies indicate a wide tissue distribution of the messenger RNA for this antigen, including the thyroid, eye muscle, parathyroid, spleen, skeletal muscle, and uterus. There were variations in the relative amounts of specific message for D1 in the different tissues, with the uterus, thyroid, and eye muscle having the greatest amount of product per microgram of total RNA. A maltose binding protein-D1 fusion protein was expressed in Escherichia coli, purified, and used to assess serologic reactivity to D1 by Western blot. Autoantibodies to this antigen were noted in 19 of 24 (78%) of Hashimoto's disease patients, 26 of 41 (63%) of Graves' disease patients, and in 9 of 17 (53%) of normal controls. Sixty percent of Graves' disease patients with clinical ophthalmopathy had antibodies to D1, as did 63% of Graves' patients without signs or symptoms of clinical ophthalmopathy. There was no correlation between reactivity to D1 and either clinical measures of hyperthyroidism or antibody titers to thyroid peroxidase or thyroglobulin. The presence of autoantibodies to this antigen in patients with Hashimoto's disease, in Graves' disease patients without ophthalmopathy and in normal controls indicate that serologic recognition of this antigen is not restricted to patients with ophthalmopathy. In addition, the expression of messenger RNA for this antigen in multiple types of cells questions the tissue specificity of this autoantigen.

Adult↗
PubMed1993

Functional analysis of the amino acids in the DNA recognition alpha-helix of the human thyroid hormone receptor.

The roles in DNA binding and transcriptional activation of individual amino acids in the putative recognition alpha-helix of the first zinc finger of the beta-isoform of the human thyroid hormone receptor (hT3R beta) have been probed by site-directed mutagenesis. Alanine substitutions of highly conserved residues involved in the folding of this zinc finger abolished the binding of hT3R beta to various thyroid response elements. A similar effect was observed for alanine substitutions of those conserved residues in hT3R beta that were expected to make specific contacts to DNA bases common to all hormone response elements. The three P-box amino acids have previously been shown to be essential for discrimination of the base pairs that differ between the DNA binding sites for related steroid/thyroid hormone receptors. In hT3R beta, the P-box residues are E, G, and G; the results of this study show that alanine substitution of the glutamic acid dramatically reduces DNA binding activity by hT3R beta, while the substitution of either glycine has little or no effect on DNA binding. The effects of alanine substitutions on hT3R beta transcriptional activation properties were consistent with the effect of these substitutions on DNA binding properties, with the exception of the second P-box amino acid. T3R beta substituted with alanine at this position is substantially more defective in transcriptional activation than it is in specific DNA binding. These results indicate that there are two separate mechanisms of response element discrimination by P-box amino acids of steroid/thyroid hormone receptors, one which operates at the level of DNA recognition and a second which operates at the level of transcriptional activation.

Amino Acid Sequence↗
PubMed1992

Chromatographic and mass spectrometric methods for determination of lysergic acid diethylamide (LSD) and metabolites in body fluids.

Continued illicit use of the potent psychedelic drug lysergic acid diethylamide (LSD) has stimulated efforts to develop effective analytical methods for detection of the drug and its metabolites in body fluids from suspected LSD users. Recently reported methods based on gas and liquid chromatography, combined with single- and multiple-stage mass spectral analysis, now permit accurate detection and quantitation of LSD at sub-nanogram/milliliter concentrations.

Body Fluids↗
PubMed1992

Determination of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD in body fluids by gas chromatography/tandem mass spectrometry.

Procedures for detection and quantitation of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD by capillary chromatography/tandem mass spectrometry (GC/MS/MS) are presented. Several methods for derivatization, sample introduction, and ionization, in combination with mass spectrometry/mass spectrometry (MS/MS), have been evaluated for overall ionization efficiency and product-ion sensitivity and specificity. Fragmentation pathways derived from low-energy collision-induced dissociation (CID) spectra of protonated LSD, and the protonated trimethylsllyl derivatives of LSD (LSD-TMS) and deuterium-labeled analogs of LSD, have been proposed. Principal dissociations primarily involve the amide and piperidine-ring moieties in which losses of CH3 radical, CH3NH2, CH3NCH2, diethylamine, diethylformamide, and N,N-diethylpropenamide from MH+ are observed. Positive-ion ammonia chemical ionization and subsequent MS/MS analysis of the protonated molecules (MH+) of the trimethylsilyl (TMS) derivatives of LSD, iso-LSD, and N-demethyl-LSD provide a high degree of specificity for identification of these compounds in urine or blood at low-pg/mL concentrations. Negative-ion chemical ionization and GC/MS/MS analysis of the molecular anion (M-) of the trifluoroacetyl (TFA) derivative is well suited for trace-level identification of N-demethyl-LSD, a metabolite of LSD.

Body Fluids↗