Neuronal hamartoma of the trigeminal sensory root associated with trigeminal neuralgia.
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Aged↗
Biomedical subjects
T Moss
Publications and source records attributed to T Moss.
Association of interleukin-1 gene polymorphisms with Alzheimer's disease.
Interleukin-1 (IL-1) is markedly overexpressed in Alzheimer's disease. We found the IL-1A 2,2 genotype in 12.9% of 232 neuropathologically confirmed Alzheimer's disease patients and 6.6% of 167 controls from four centers in the United Kingdom and United States (odds ratio, 3.0; controlled for age and for ApoE [apolipoprotein E] genotype). Homozygosity for both allele 2 of IL-1A and allele 2 of IL-1B conferred even greater risk (odds ratio, 10.8). IL-1 genotypes may confer risk for Alzheimer's disease through IL-1 overexpression and IL-1-driven neurodegenerative cascades.
Aged↗
The cytoskeletal effector xPAK1 is expressed during both ear and lateral line development in Xenopus.
xPAK1, a probable effector of stress activated MAP-kinase SAPK1/JNK activation and cytoskeletal dynamics, was found to be ubiquitously expressed within the Xenopus laevis ear and lateral line system during the development and differentiation of these organs. xPAK1 expression was very strong in the otic placode from its condensation, and expression continued in the otic vesicle up until stage 35/36, after which it abruptly ceased. At stage 29/30 expression occurred specifically in the epithelium of the otic vesicle, which includes the prospective sensorial epithelium. Expression of xPAK1 was also observed in the lateral line system from stage 35/36, at which stage the lateral line primordia have begun to migrate from the region of the otic vesicle. Lateral line expression continued at least until stage 37/38, at which time xPAK1 was noted in association with the differentiating lateral line organs. To our knowledge, xPAK1 is the first ubiquitous lateral line marker that is also expressed in the ear. In the context of previous studies, our data suggest that xPAK1 either plays a role in the differentiation of the mechano-sensors of the auditory system or in the formation of the otic vesicle epithelium and the lateral line primordia.
Age Factors↗
The effect of neuraxial steroids on weight and bone mass density: a prospective evaluation.
The deleterious effects of corticosteroids utilized in neural blockade are a commonly discussed and contentious issue. Corticosteroids are considered to have widespread effects on almost all body systems, with suppression of the release of corticotropin (ACTH) from the pituitary suppressing the secretion of endogenous corticosteroids, thus producing a secondary adrenocortical insufficiency. Even though a multitude of complications of neuraxial steroids have been popularized, the more practical complications of corticosteroid administration are twofold - those resulting from withdrawal and those resulting from continued use of large doses. These mainly include suppression of the pituitary-adrenal axis, weight gain, osteopenia, osteoporosis, and a variety of other minor complications. This prospective evaluation was undertaken to evaluate the effect of corticosteroids and the dose relationship on weight gain, bone-mass density (BMD), and other deleterious effects of steroids. The study population consisted of 204 patients; however, complete data were available on only 123 patients. These patients were divided into two groups, with group I receiving neural blockade without any steroids, and, Group II consisting of patients receiving neuraxial steroids. The results of serial determination of weight and BMD showed no significant change at any interval or at the end of 1 year in all 123 patients with or without steroid administration. In addition, this study also showed some improvement in BMD, as well as weight reduction indicating improvement in functional status. It is concluded that low-dose administration of neuraxial steroids is safe in patients suffering with chronic pain who have failed to respond to conservative modalities of treatment with a favorable risk-benefit ratio. This study also showed no deleterious effect on weight or BMD.
Journal Article↗
Identification of a mammalian RNA polymerase I holoenzyme containing components of the DNA repair/replication system.
Traditional models for transcription initiation by RNA polymerase I include a stepwise assembly of basic transcription factors/regulatory proteins on the core promoter to form a preinitiation complex. In contrast, we have identified a preassembled RNA polymerase I (RPI) complex that contains all the factors necessary and sufficient to initiate transcription from the rDNA promoter in vitro. The purified RPI holoenzyme contains the RPI homolog of TFIID, SL-1 and the rDNA transcription terminator factor (TTF-1), but lacks UBF, an activator of rDNA transcription. Certain components of the DNA repair/replication system, including Ku70/80, DNA topoisomerase I and PCNA, are also associated with the RPI complex. We have found that the holo-enzyme supported specific transcription and that specific transcription was stimulated by the RPI transcription activator UBF. These results support the hypothesis that a fraction of the RPI exists as a preassembled, transcriptionally competent complex that is readily recruited to the rDNA promoter, i.e. as a holoenzyme, and provide important new insights into the mechanisms governing initiation by RPI.
Animals↗
Cellular regulation of ribosomal DNA transcription:both rat and Xenopus UBF1 stimulate rDNA transcription in 3T3 fibroblasts.
A novel RNA polymerase I (RPI) driven reporter gene has been used to investigate the in vivo role of the architectural ribosomal transcription factor UBF in gene activation and species specificity. It is shown that the level of UBF overexpression in NIH3T3 cells leads to a proportionate increase in the activities of both reporter and endogenous ribosomal genes. Further, co-expression of UBF antisense RNA suppresses reporter gene expression. Thus, UBF is limiting for ribosomal transcription in vivo and represents a potential endogenous ribosomal gene regulator. In contrast to some in vitro studies, in vivo, the mammalian and Xenopus forms of UBF1 show an equal ability to activate a mouse RPI promoter. This activity is severely impaired in mutants compromised for either dimerization or DNA binding. Similarly, the natural UBF2 splice variant shows a severely impaired capacity to activate RPI transcription. The data strongly suggest that UBF predominantly regulates ribosomal transcription by binding to and activating the ribosomal genes, but does not eliminate a possible secondary role in titrating ribosomal gene repressors such as Rb. Consistent with the DNA folding ability and cellular abundance of the UBF, we suggest that the protein may regulate a structural transition between the potentially active and active chromatin states.
3T3 Cells↗
Profile of placental alkaline phosphatase expression in human malignancies: effect of tumour cell activation on alkaline phosphatase expression.
Cellular alkaline phosphatases (ALP) are increasingly recognised as important markers for monitoring tumour cell behaviour in human malignancies. Colorimetric, flow-cytometric, and immunocytochemical assays were employed to assess the influence of activation on expression of cellular ALP in human tumour cell lines. The results showed the following: (1) Testis tumour biopsies (16/16) unlike bladder (0/14) and head and neck (0/16) tumours showed positive staining for ALP, particularly the placental type, i.e. PLAP, although this was not always present on all the cells of non-seminoma biopsies. (2) The intensity of ALP expression differed widely in tumour cell lines. Based on biochemical analysis, the profile of ALP fell into two categories: (a) low expressing (MW 70 kD, placental type ALP) like Hep2 and KB lines, and (b) those expressing both low and high molecular (MW 95 kD) bands like testis lines Tera II and Ep2102. In all cases treatment of tumour cell lysates with heat prior to biochemical analysis showed the disappearance of the higher and sharpening of the lower molecular weight ALP band. (3) Exposure of tumour cells to epidermal growth factor (EGF) expressing EGF receptor led to a decreased ALP expression by as much as 54% as assessed by biochemical or flow-cytometric techniques. These data demonstrated that testis tumour tissues and cell lines expressed ALP which were different from others. The data also showed that exposure of tumour cell lines expressing EGFr to EGF resulted in suppression of ALP expression. These observations are consistent with the notion that EGFr and PLAP expression may be taken as a marker of proliferation and differentiation in human malignancies, respectively.
Alkaline Phosphatase↗
A ribosomal orphon sequence from Xenopus laevis flanked by novel low copy number repetitive elements.
We have used a differential cloning approach to isolate ribosomal/non-ribosomal frontier sequences from Xenopus laevis. A ribosomal intergenic spacer sequence (IGS) was cloned and shown not to be physically linked with the ribosomal locus. This ribosomal orphon contained the IGS sequences found immediately downstream of the 28S gene and included an array of enhancer repetitions and a non-functional spacer promoter. The orphon sequence was flanked by a member of the novel 'Frt' low copy repetitive element family. Three individual Frt repeats were sequenced and all members of this family were shown to lie clustered at two chromosomal sites, one of which contained the ribosomal orphon. One of the Frt elements contained an insertion of 297 bp that showed extensive homology to sequences within at least three other Xenopus genes. Each homology region was flanked by members of the T2 family of short interspersed repetitive elements, (SINEs), and by its target insertion sequence, suggesting multiple translocation events. The data are discussed in terms of the evolution of the ribosomal gene locus.
Animals↗
Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a model to estimate absorbed radiation dose.
PURPOSE: Previously we have demonstrated that radioimmunoconjugates can be injected into glioma resection cavities to deliver a boost of radiation to the cavity edge with little toxicity to the normal brain. In the mathematical models we have previously published to assist in the development of this strategy we assumed that antibody remains associated with the cavity edge and no diffusion occurs. However, moderate diffusion might be beneficial while, if this were excessive, it would decrease the therapeutic index markedly. METHODS AND MATERIALS: Selected individuals with relapsed malignant glioma underwent further surgical debulking; 90Y MoAb radioimmunotherapy; and open biopsy to determine the extent to which the conjugate diffuses from the cavity edge. Samples from these patients were taken in radial tracts and the corrected activity in each sample was plotted against distance from the cavity wall to determine appropriate diffusion constants. RESULTS: Our data indicates that diffusion of radioimmunoconjugate from the edge of a glioma resection cavity appears to be an exponential process. The mean Ro for each patients data set ranged from 0.48-0.63 (overall mean 0.6) cm. A dosimetric model was developed that translates these measurements into estimates of radiation dose. Applying the clinical data to this model indicates that, in each patient, the peak dose is delivered 0.16-0.18 cm below the cavity margin, and the mean dose at 2 cm deep is 5.3% (4.4-5.8%) of the peak. CONCLUSION: The model described can be used to translate diffusion constants measured by any method into estimates of absorbed radiation dose. Assuming similar diffusion kinetics, it can also be used to predict the dose deposited if alternative radionuclides are linked to MoAb, although the effect of dose rate should also be considered. In the future, it may be possible to manipulate diffusion by using either different antibodies or antibody fragments for intracavity radioimmunotherapy. Before this can be done, however, further data are needed and a noninvasive approach to measuring diffusion would clearly be optimal.
Antibodies, Monoclonal↗
Affinity purification of mammalian RNA polymerase I. Identification of an associated kinase.
Overlapping cDNA clones encoding the two largest subunits of rat RNA polymerase I, designated A194 and A127, were isolated from a Reuber hepatoma cDNA library. Analyses of the deduced amino acid sequences revealed that A194 and A127 are the homologues of yeast A190 and A135 and have homology to the beta' and beta subunits of Escherichia coli RNA polymerase I. Antibodies raised against the recombinant A194 and A127 proteins recognized single proteins of approximately 190 and 120 kDa on Western blots of total cellular proteins of mammalian origin. N1S1 cell lines expressing recombinant His-tagged A194 and FLAG-tagged A127 proteins were isolated. These proteins were incorporated into functional RNA polymerase I complexes, and active enzyme, containing FLAG-tagged A127, could be immunopurified to approximately 80% homogeneity in a single chromatographic step over an anti-FLAG affinity column. Immunoprecipitation of A194 from 32P metabolically labeled cells with anti-A194 antiserum demonstrated that this subunit is a phosphoprotein. Incubation of the FLAG affinity-purified RNA polymerase I complex with [gamma-32P]ATP resulted in autophosphorylation of the A194 subunit of RPI, indicating the presence of associated kinase(s). One of these kinases was demonstrated to be CK2, a serine/threonine protein kinase implicated in the regulation of cell growth and proliferation.
Amino Acid Sequence↗
High-dose chemotherapy in patients with breast cancer: evaluation of infusing peripheral blood stem cells containing occult tumor cells.
The purpose of this study was to evaluate the frequency of detecting occult tumor cells in peripheral blood stem cell (PBSC) harvests and to determine the impact of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral blood stem cell harvests from 223 patients with breast cancer were examined by an immunocytochemistry (ICC) method for detection of occult tumor cells, and infused after HDC without consideration of test results. Two hundred and four patients, 114 with stage II-III and 90 with stage IV disease who received only PBSC, that were tested by ICC were evaluated for time to relapse. Five hundred and eighty-one of 619 PBSC harvests (94%) from 223 patients were tested. Fifty-three of 581 harvests (9%), 8% from stage II-III and 10% from stage IV patients, were positive by ICC (P = 0.68). Forty-one of 223 patients (18%), 17/122 (14%) with stage II-III and 24/101 (24%) with stage IV disease, had positive harvests (P = 0.06). Eleven percent of patients who had 1-2 harvests tested were positive as compared to 32% of patients who had > or =3 PBSC harvests tested (P < 0.001). Nineteen patients who were infused with a mixture of ICC negative and untested PBSC harvests were excluded from analyses of relapse. The probabilities of relapse at 18 months for the 97 patients with stage II-III disease infused with ICC-negative and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48). The probabilities of relapse at 18 months for patients achieving a CR or a CR in non-bone sites and improvement in bone lesions were 0.55 for the ICC-negative group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was concluded that occult tumor cells were detected by ICC in PBSC harvests from a relatively small fraction of women with breast cancer, but were not associated with a significant increase in the probability of early relapse or progression when infused after HDC.
Adult↗
Congenital multiple annular glomus tumors.
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Child, Preschool↗
Reticulate hyperpigmentation of the skin after topical application of benzoyl peroxide.
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Acne Vulgaris↗
UV-laser crosslinking of proteins to DNA.
Photochemical crosslinking is now a powerful method for studying protein-nucleic acid interactions. UV light is a zero-length crosslinking agent that predominantly or exclusively crosslinks proteins to nucleic acids at their contact points. It can therefore provide strong evidence for close protein-nucleic acid interactions. However, to achieve an acceptable degree of crosslinking with conventional UV light sources, exposure times ranging from minutes to several hours are necessary. Such prolonged irradiation allows for the artifactual redistribution of proteins and precludes kinetic studies. The use of UV lasers overcomes these difficulties since the number of photons required for the crosslinking may be delivered in time intervals on the order of nano- or even picoseconds. We described detailed procedures for UV laser-induced protein-DNA crosslinking both in vivo and in vitro. Technical aspects, including the choice of UV laser for irradiation, the isolation of covalently crosslinked protein-DNA complexes, immunochemical techniques for both the identification and isolation of specific protein-DNA complexes and the identification of the crosslinked DNA sequences, are reviewed in detail. The application of UV laser crosslinking in kinetic studies is illustrated by the example of the TATA-binding protein (TBP) interaction with the adenovirus E4 promoter.
Adenoviridae↗
Exercise enhances creativity independently of mood.
OBJECTIVES: It has been widely accepted in the literature that various forms of physical exercise, even in a single session, enhance positive mood. It has also been shown that physical exercise may sometimes enhance creative thinking, but the evidence is inconclusive. Positive moods can favour creative thinking, but the opposite has also been reported and these relations are unclear. There is a large anecdotal literature suggesting that creative people sometimes use bodily movement to help overcome "blocks". The aim of this study was to establish whether post-exercise creative thinking was attributable to improved mood. METHODS: The responses of 63 participants to an exercise (aerobic workout or aerobic dance) and a "neutral" video watching condition were compared. Mood was measured using an adjective list, and creative thinking was tested by three measures of the Torrance test. RESULTS: Analysis of variance showed a large and significant increase in positive mood after exercise (P < 0.001) and a significant decrease in positive mood after video watching (P < 0.001). A significant increase between the creative thinking scores of the two conditions was found on the flexibility (variety of responses) measure (P < 0.05). A multifactorial analysis of all data failed to show a significant covariance of creative thinking with the two measures of mood (P > 0.05). CONCLUSIONS: These results suggest that mood and creativity were improved by physical exercise independently of each other.
Adult↗
Teflon-induced granuloma following treatment of trigeminal neuralgia by microvascular decompression. Report of two cases.
The authors report two cases of Teflon-induced granuloma occurring as a result of microvascular decompression using Teflon wool for the treatment of trigeminal neuralgia (TN). Teflon, which is used to separate a compressing vessel from the root entry zone (REZ) of the trigeminal nerve at the brainstem, is presumed to be an inert material. In the two cases reported here, however, Teflon induced a foreign body reaction at the REZ, causing recurrence of TN. The patients' pain was cured by complete decompression or partial sensory rhizotomy of the trigeminal sensory root at reoperation. Teflon-induced granuloma has occurred in 1.3% of the authors' series of 155 patients with TN treated using microvascular decompression. Recommendations for avoiding this complication are offered.
Aged↗
Antisense and sense poly(A)-RNAs from the Xenopus laevis pyruvate dehydrogenase gene loci are regulated with message production during embryogenesis.
The structure and temporal expression of two Xenopus cDNAs encoding the beta subunit of pyruvate dehydrogenase (XPdhE1 beta) have been determined. XPdhE1 beta was 88% homologous to mature human PdhE1 beta, but the putative N-terminal mitochondrial signal peptide was poorly conserved. Zygotic expression of XPdhE1 beta mRNA was detected at neural tube closure and increased until stage 40. RT-PCR cloning identified a short homology to a protein kinase open reading frame within the 3' non-coding sequence of the XPdhE1 beta cDNAs. This homology, which occurred on the antisense cDNA strand, was shown by strand specific RT-PCR to be transcribed in vivo as part of an antisense RNA. Northern analysis showed that this RNA formed part of an abundant and heterogeneous population of antisense and sense poly(A)-RNAs transcribed from the XPdhE1 beta loci and coordinately regulated with message production.
Amino Acid Sequence↗
The DNA supercoiling architecture induced by the transcription factor xUBF requires three of its five HMG-boxes.
The formation of a near complete loop of DNA is a striking property of the architectural HMG-box factor xUBF. Here we show that DNA looping only requires a dimer of Nbox13, a C-terminal truncation mutant of xUBF containing just HMG-boxes 1-3. This segment of xUBF corresponds to that minimally required for activation of polymerase I transcription and is sufficient to generate the major characteristics of the footprint given by intact xUBF. Stepwise reduction in the number of HMG-boxes to less than three significantly diminishes DNA bending and provides an estimate of bend angle for each HMG-box. Together the data indicate that a 350 +/- 16 degree loop in 142 +/- 30 bp of DNA can be induced by binding of the six HMG-boxes in an Nbox13 dimer and that DNA looping is probably achieved by six in-phase bends. The positioning of each HMG-box on the DNA does not predominantly involve DNA sequence recognition and is thus an intrinsic property of xUBF.
Binding Sites↗