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T Moss

Publications and source records attributed to T Moss.

At least 55 records · Page 3Linked to original sources
PubMed1996

Overexpression of the transcription factor UBF1 is sufficient to increase ribosomal DNA transcription in neonatal cardiomyocytes: implications for cardiac hypertrophy.

The accelerated protein accumulation characteristic of cardiomyocyte hypertrophy results from increased cellular protein synthetic capacity (elevated ribosome content). The rate limiting step in ribosome accumulation is transcription of the rRNA genes. During neonatal cardiomyocyte hypertrophy induced by norepinephrine or spontaneous contraction, changes in the expression of a ribosomal DNA transcription factor, UBF, correlated with increased rates of ribosome biogenesis. We hypothesized that elevated expression of UBF was part of the mechanism by which these hypertrophic stimuli effected increases in the rate of transcription from the rDNA promoter. In this study, we have examined directly the effect of overexpressing UBF on rDNA transcription in neonatal cardiomyocytes in culture. In control experiments, a novel reporter construct for rDNA transcription (pSMECAT) showed similar increases in activity in response to hypertrophic stimuli (10(-4) M phenylephrine, 10(-7) M endothelin, and spontaneous contraction) as did the endogenous rRNA genes. When contraction-arrested cardiomyocytes were cotransfected with pSMECAT and increasing amounts of a UBF1 expression vector; a dose-dependent (3-5 fold) increase in rDNA transcription was observed. Western blot analysis confirmed that the overexpressed, FLAG-tagged UBF accumulated in the cardiomyocyte nuclei. The observation that overexpression of UBF1 is sufficient to increase rDNA transcription in neonatal cardiomyocytes provides evidence in support of the hypothesis that the regulation of UBF is a key component of the increased ribosome biogenesis and protein accumulation associated with cardiomyocyte hypertrophy.

Animals↗
PubMed1996

Event-related potentials--neurophysiological tools for predicting emergence and early outcome from traumatic coma.

OBJECTIVE: To determine the prognostic value of multimodal evoked potentials (EPs) and event-related (ERPs) potentials in coma (Glasgow Coma Score <8), after severe traumatic brain injury (TBI). DESIGN: Prospective, longitudinal study of neurophysiological responses recorded during traumatic coma. SETTING: Intensive Care Unit, Frenchay Hospital, Bristol, UK. PARTICIPANTS: Fifty-four comatose TBI patients (age range 1-80 years, mean 36.4). METHODS: Neurophysiological responses were recorded from 11 scalp electrodes with earlobe reference. Conduction times were measured for brainstem auditory, flash visual and somatosensory, short-latency EPs. Peak latencies and amplitudes were determined for long-latency components of visual and auditory ERPs, generated by passive "oddball" paradigms. These neurophysiological and various clinical parameters were correlated with patient outcome using Pearson's coefficient. MAIN OUTCOME MEASURE: Three month Glasgow Outcome Scale (GOS). RESULTS AND CONCLUSION: Highly significant (P <0.001) correlations exist between long-latency ERP components and 3-month outcome. Short-latency EPs, brainstem (wave I-V) and somatosensory conduction times also correlate significantly with the GOS (P <0.01). Of the clinical measurements, pupillary response patterns, APACHE II and Glasgow Coma Scores (GCS) correlate significantly with outcome, as do the retrospective measures of duration of coma and post-traumatic amnesia (PTA) in survivors. Unfortunately, due to variance of long-latency responses, even in controls, absolute values cannot be relied upon as prognosticators. The presence of "mismatch negativity" predicted the return of consciousness (89.7% sensitivity and 100% specificity) and preceded changes in GCS. Its latency was the single best indicator of 90-day outcome from coma (r = -0.641).

Acoustic Stimulation↗
PubMed1996

Inactivation of topoisomerase I or II may lead to recombination or to aberrant replication termination on both SV40 and yeast 2 micron DNA.

Topoisomerase I is believed to be sufficient for early replication of circular viral genomes such as those of SV40 and of yeast plasmids. Topoisomerase II is required for the decatenation of the daughter genomes and probably also for fork elongation during the later stages of SV40 replication. Using the neutral-neutral two-dimensional gel system, we have followed the progression of replication of both SV40 and the yeast 2 micron plasmid under various conditions of topoisomerase inhibition. During SV40 replication, inhibition of topoisomerase II by VP16, VM26 or hypertonic shock (but not by merbarone), and inhibition of topoisomerase I by camptothecin all led to the accumulation of aberrant DNA structures containing two almost completely replicated genomes. These aberrant structures resembled either recombination intermediates or late Cairns structures in which the site of replication termination had shifted and now mapped to a continuum of sites throughout the genome. Replication of the 2 micron plasmid in a topoisomerase II- but not a topoisomerase I-deficient yeast gave rise to very similar structures. The data suggest that inactivation of topoisomerase I or II either stimulates recombination or, by differentially affecting replication fork progression, leads to aberrant replication termination.

Camptothecin↗
PubMed1996

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases.

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone-secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

Acromegaly↗
PubMed1996

Catalytic and non-catalytic forms of the neurotrophin receptor xTrkB mRNA are expressed in a pseudo-segmental manner within the early Xenopus central nervous system.

The induction of anterior-posterior and medio-lateral patterning within the Xenopus neural plate leads to the rapid establishment of a functional nervous system. Here we describe two Xenopus TrkB neurotrophin receptor genes which are expressed in discrete sets of neuroblasts during this developmental process. The xTrkB mRNAs encode both catalytic and non-catalytic receptors and exhibit membrane-spanning-domain proximal splicing. Expression begins at neural tube closure within the trigeminal ganglion and within the Rohon-Beard neurons of the dorsal spinal cord, providing an excellent dorsal marker of early neural tube patterning. Expression occurs later in the facial ganglia and possibly within the Kolmer-Agduhr neurons. The predominant xTrkB transcripts within the trigeminal and Rohon-Beard neurons and the exclusive early transcripts of the facial ganglia encode C-terminally truncated non-catalytic receptors. Such Trk mRNAs have previously been observed in rodents. However, our observations suggest that they may play a specific role during early development. Anterior-posterior segmentation of the neural tube occurs rostrally within the prospective brain, but previous studies have suggested that segmentation does not extend caudally into the spinal cord. We show that the xTrkB positive Rohon-Beard neurons of the spinal cord do in fact display clear segmental groupings soon after neural tube closure. This is consistent with a role for segmentation in the anterior-posterior patterning of the trunk central nervous system.

Amino Acid Sequence↗
PubMed1995

Congenital astroblastoma: an immunohistochemical study. Case report.

Astroblastoma is a rare type of glial tumor, usually occurring in older children and young adults. It has a distinctive histological appearance that is characterized by a radiating arrangement of tumor cells that form perivascular pseudorosettes. The authors report only the second case of astroblastoma presenting in congenital form. Following subtotal tumor resection, the infant received 10 courses of chemotherapy consisting of vincristine, etoposide, and carboplatinum. Evidence is presented for a tumor response to chemotherapy, a previously unreported observation. The child is alive 2.5 years after diagnosis with satisfactory functional status. Immunohistological and ultrastructural features of this tumor are presented. The discussion focuses on the biology, natural history, and management of this unusual neoplasm.

Astrocytoma↗
PubMed1994

Short-range DNA looping by the Xenopus HMG-box transcription factor, xUBF.

Xenopus UBF (xUBF) interacts with DNA by way of multiple HMG-box domains. When xUBF binds to the ribosomal promoter, the carboxyl-terminal acidic tail and amino-terminal HMG-box interact. Binding also leads to negative DNA supercoiling and the formation of a disk-like structure, the enhancesome. Within the enhancesome, an xUBF dimer makes a low-density protein core around which DNA is looped into a single 180-base pair turn, probably by in-phase bending. The enhancesome structure suggests a mechanism for xUBF-dependent recruitment of the TATA box-binding protein complex without direct interaction between the two factors.

Animals↗
PubMed1994

Aerobic exercise and Type A behaviour.

The Type A behaviour pattern is a well-documented, if controversial, risk factor for coronary heart disease. Surprisingly, relatively little work has been reported on ways of modifying this behaviour pattern. Aerobic exercise, with its demonstrated benefits for both cardiovascular reactivity and psychological 'well-being', is a promising treatment. The literature is reviewed and recommendations are made for practical applications and future research.

Behavior Therapy↗
PubMed1994

An analysis of Xenopus tyrosine kinase genes and their expression in early development.

Xenopus laevis and X. borealis were screened for tyrosine kinase genes using the polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR and 34 X. laevis and 23 X. borealis tyrosine genes were identified. Eighteen of the genes represented novel tyrosine kinase family members. The rest could be classified into known tyrosine kinase subfamilies, of which however only three have been previously identified in Xenopus. Eight clones, including bFGFR (xFGFR1) and potential Trk, Ins R., Fak, Fyn, and Abl homologs, were used to probe temporal and spatial gene expression in early development. Quantitative RT-PCR and whole-mount and in situ hybridization showed that most of these mRNAs were present throughout development and were broadly distributed, mainly in ectodermal and mesodermal derived tissues. At the blastula stage, bFGFR mRNA was detected within the ectoderm and a gradient of expression was noted within the invaginating mesoderm. The unexpected promiscuous expression of many tyrosine kinase genes in early development is discussed.

Amino Acid Sequence↗
PubMed1994

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES: The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN: Randomised, double-blind parallel group study. SETTING: Multicentre study in six genitourinary clinics within the U.K. PATIENTS: One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES: Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS: At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS: At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.

Adolescent↗
PubMed1994

Cervical lymph nodes metastases from a pituitary carcinoma.

The authors report a case of a pituitary carcinoma which was locally invasive and which metastasized to cervical lymph nodes more than 9 years after the initial presentation. Cells from the tumour and metastasis immunostained with antibodies to prolactin and growth hormone, even though there was no clinical or biochemical evidence that the tumour was secreting prolactin or growth hormone. In addition, ultrastructural studies showed a monomorphic tumour with secretory granules much smaller than those normally associated with prolactin and growth hormone secretion. The clinical and pathological features suggest that the tumour is probably an acidophil stem cell adenoma, which although known to be aggressive in its clinical behaviour has not been previously reported to metastasize.

Adenoma, Chromophobe↗
PubMed1993

Recognition of the Xenopus ribosomal core promoter by the transcription factor xUBF involves multiple HMG box domains and leads to an xUBF interdomain interaction.

The interaction of the ribosomal transcription factor xUBF with the RNA polymerase I core promoter of Xenopus laevis has been studied both at the DNA and protein levels. It is shown that a single xUBF-DNA complex forms over the 40S initiation site (+1) and involves at least the DNA sequences between -20 and +60 bp. DNA sequences upstream of +10 and downstream of +18 are each sufficient to direct complex formation independently. HMG box 1 of xUBF independently recognizes the sequences -20 to -1 and +1 to +22 and the addition of the N-terminal dimerization domain to HMG box 1 stabilizes its interaction with these sequences approximately 10-fold. HMG boxes 2/3 interact with the DNA downstream of +22 and can independently position xUBF across the initiation site. The C-terminal segment of xUBF, HMG boxes 4, 5 or the acidic domain, directly or indirectly interact with HMG box 1, making the core promoter sequences between -11 and -15 hypersensitive to DNase. This interaction also requires the DNA sequences between +17 and +32, i.e. the HMG box 2/3 binding site. The data suggest extensive folding of the core promoter within the xUBF complex.

Amino Acid Sequence↗