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1.  Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome 
Neurology  2011;76(22):1903-1910.
Objective:
The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features.
Methods:
Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia.
Results:
The reported age at onset range was 39–71 years, and symptom duration was 3–38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared.
Conclusions:
Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Neurology® 2011;76:1903–1910
doi:10.1212/WNL.0b013e31821d746e
PMCID: PMC3115806  PMID: 21624989
2.  Influence of Single Nucleotide Polymorphisms in COMT, MAO-A and BDNF Genes on Dyskinesias and Levodopa Use in Parkinson’s Disease 
Neuro-degenerative diseases  2013;13(1):24-28.
Background
Clinical heterogeneity in the development of levodopa-induced dyskinesias (LID) suggests endogenous factors play a significant role in determining their overall prevalence.
Objective
We hypothesised that single nucleotide polymorphisms (SNPs) in specific genes may result in a clinical phenotype conducive to an increased risk of LID.
Methods
We examined the influence of SNPs in the catechol-O-methyltransferase (COMT), monoamine oxidase A (MAO-A) and brain-derived neurotrophic factor (BDNF) genes on LID in a cohort of 285 pathologically confirmed Parkinson’s disease patients, using data from their complete disease course.
Results
Dyskinetic patients demonstrated younger age at disease onset (60.3 vs. 66.4 years, p < 0.0001), a longer disease duration (17.0 vs. 12.0 years, p < 0.0001) and a higher maximum daily levodopa equivalent dose (LED; 926.7 vs. 617.1 mg/day, p < 0.0001) than patients without dyskinesias. No individual SNP was found to influence prevalence or time to onset of dyskinesias, including after adjustment for known risk factors. We observed that patients carrying alleles conferring both high COMT activity and increased MAO-A mRNA expression received significantly higher maximum and mean daily LEDs than those with low enzyme activity/mRNA expression (max LED: 835 ± 445 vs. 508 ± 316 mg; p = 0.0056, mean LED: 601 ± 335 vs. 398 ± 260 mg; p = 0.025).
Conclusions
Individual SNPs in BDNF, COMT and MAO-A genes did not influence prevalence or time to onset of dyskinesias in this cohort. The possibility that combined COMT and MAO-A genotype is a significant factor in determining an individual’s lifetime levodopa exposure warrants further investigation.
doi:10.1159/000351097
PMCID: PMC4194629  PMID: 24008922
Parkinson’s disease; Levodopa-induced dyskinesias; Catechol-O-methyltransferase; Monoamine oxidase A; Brain-derived neurotrophic factor
4.  Second to fourth digit ratio (2D : 4D), breast cancer risk factors, and breast cancer risk: a prospective cohort study 
British Journal of Cancer  2012;107(9):1631-1636.
Background:
We aimed to assess whether 2D : 4D measures are associated with breast cancer risk.
Methods:
We derived the ratio of the lengths of the index and ring fingers (2D : 4D), and right minus left 2D : 4D (Δr−l) from digit lengths measured from photocopies of participants' hands collected during a recent follow-up of the Melbourne Collaborative Cohort Study, a prospective study including 24 469 women. Of the 9044 women with available data, we identified 573 incident breast cancer cases. Hazard ratios (HR) and 95% confidence intervals (CI) for a one standard deviation difference in 2D : 4D measures were obtained from Weibull survival models, and linear regression models were used to examine potential associations between 2D : 4D measures and age at menarche and menopause.
Results:
We found a direct association between left 2D : 4D and breast cancer risk, an inverse association between Δr−l and risk of breast cancer, but no association between right 2D : 4D and breast cancer risk. Among breast cancer cases, both right 2D : 4D and Δr−l were inversely associated with age at diagnosis. We also observed associations between both right 2D : 4D and Δr−l and age at menopause, with increasing digit ratio measures related to earlier mean age at menopause.
Conclusion:
Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer. If confirmed in other studies, this suggests that lower exposure or sensitivity to prenatal testosterone might be associated with lower risk of breast cancer.
doi:10.1038/bjc.2012.418
PMCID: PMC3493764  PMID: 22990654
breast cancer; hormones; digit ratio; 2D : 4D; prenatal hormones
5.  Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk 
Stevens, K N | Garcia-Closas, M | Fredericksen, Z | Kosel, M | Pankratz, V S | Hopper, J L | Dite, G S | Apicella, C | Southey, M C | Schmidt, M K | Broeks, A | Van ‘t Veer, L J | Tollenaar, R A E M | Fasching, P A | Beckmann, M W | Hein, A | Ekici, A B | Johnson, N | Peto, J | dos Santos Silva, I | Gibson, L | Sawyer, E | Tomlinson, I | Kerin, M J | Chanock, S | Lissowska, J | Hunter, D J | Hoover, R N | Thomas, G D | Milne, R L | Pérez, JI Arias | González-Neira, A | Benítez, J | Burwinkel, B | Meindl, A | Schmutzler, R K | Bartrar, C R | Hamann, U | Ko, Y D | Brüning, T | Chang-Claude, J | Hein, R | Wang-Gohrke, S | Dörk, T | Schürmann, P | Bremer, M | Hillemanns, P | Bogdanova, N | Zalutsky, J V | Rogov, Y I | Antonenkova, N | Lindblom, A | Margolin, S | Mannermaa, A | Kataja, V | Kosma, V-M | Hartikainen, J | Chenevix-Trench, G | Chen, X | Peterlongo, P | Bonanni, B | Bernard, L | Manoukian, S | Wang, X | Cerhan, J | Vachon, C M | Olson, J | Giles, G G | Baglietto, L | McLean, C A | Severi, G | John, E M | Miron, A | Winqvist, R | Pylkäs, K | Jukkola-Vuorinen, A | Grip, M | Andrulis, I | Knight, J A | Glendon, G | Mulligan, A M | Cox, A | Brock, I W | Elliott, G | Cross, S S | Pharoah, P P | Dunning, A M | Pooley, K A | Humphreys, M K | Wang, J | Kang, D | Yoo, K-Y | Noh, D-Y | Sangrajrang, S | Gabrieau, V | Brennan, P | McKay, J | Anton-Culver, H | Ziogas, A | Couch, F J | Easton, D F
British Journal of Cancer  2011;105(12):1934-1939.
Background:
Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.
Methods:
A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).
Results:
Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95–0.99, P=4.6 × 10−3), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96–1.01, P=0.139).
Conclusion:
Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer
doi:10.1038/bjc.2011.448
PMCID: PMC3251877  PMID: 22033276
genetic susceptibility; neoplasms; association study
6.  Dietary patterns and risk of breast cancer 
British Journal of Cancer  2010;104(3):524-531.
Background:
Evidence is emerging that prudent/healthy dietary patterns might be associated with a reduced risk of breast cancer.
Methods:
Using data from the prospective Melbourne Collaborative Cohort Study, we applied principal factor analysis to 124 foods and beverages to identify dietary patterns and estimated their association with breast cancer risk overall and by tumour characteristics using Cox regression.
Results:
During an average of 14.1 years of follow-up of 20 967 women participants, 815 invasive breast cancers were diagnosed. Among the four dietary factors that we identified, only that characterised by high consumption of fruit and salad was associated with a reduced risk, with stronger associations observed for tumours not expressing oestrogen (ER) and progesterone receptors (PR). Compared with women in the lowest quintile of the factor score, the hazard ratio for women in the highest quintile was 0.92 (95% confidence interval (CI)=0.70–1.21; test for trend, P=0.5) for ER-positive or PR-positive tumours and 0.48 (95% CI=0.26–0.86; test for trend, P=0.002) for ER-negative and PR-negative tumours (test for homogeneity, P=0.01).
Conclusion:
Our study provides additional support for the hypothesis that a dietary pattern rich in fruit and salad might protect against invasive breast cancer and that the effect might be stronger for ER- and PR-negative tumours.
doi:10.1038/sj.bjc.6606044
PMCID: PMC3049555  PMID: 21157446
breast cancer; dietary patterns; factor analysis; prospective study
8.  BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received 
British Journal of Cancer  2010;103(5):668-675.
Background:
Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker.
Methods:
Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2.
Results:
In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66–0.88, P<0.001). BCL2 was a powerful prognostic marker in ER− (HR 0.63, 95% CI 0.54–0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48–0.65, P<0.001), and in HER2− (HR 0.55, 95% CI 0.49–0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57–0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039).
Conclusions:
BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work is now needed to ascertain the exact way to apply BCL2 testing for risk stratification and to standardise BCL2 immunohistochemistry for this application.
doi:10.1038/sj.bjc.6605736
PMCID: PMC2938244  PMID: 20664598
BCL2; breast cancer; prognosis
9.  Decreased Muscarinic Receptor Binding in the Frontal Cortex of Bipolar Disorder and Major Depressive Disorder Subjects 
Journal of affective disorders  2008;116(3):184-191.
Background
Dysfunction of the cholinergic muscarinic receptors has been implicated in the pathology of bipolar disorder and major depressive disorder. However, there is conflicting evidence regarding the association between individual muscarinic receptors and the two disorders.
Methods
We used the muscarinic receptor selective radioligands [3H]pirenzepine, [3H]AFDX-384 and [3H]4-DAMP to measure the levels of muscarinic1 (CHRM1) and muscarinic4 (CHRM4) receptors, muscarinic2 (CHRM2) and muscarinic4 (CHRM4) receptors and muscarinic3 (CHRM3) receptor, respectively. Radioligand binding was measured in Brodmann’s area (BA) 10 of the rostral prefrontal cortex, BA 46 of the dorsolateral prefrontal cortex and BA 40 of the parietal cortex in the post-mortem CNS from subjects with bipolar disorder or major depressive disorder and control subjects.
Results
[3H]AFDX-384 binding was decreased in BA 46 in both bipolar disorder (p<0.01) and major depressive disorder (p<0.05). [3H]4-DAMP binding was decreased in BA 10 in bipolar disorder (p<0.05) but not major depressive disorder (p>0.05). [3H]AFDX-384 and [3H]4-DAMP binding were unaltered in any other cortical region examined for either disorder (p>0.05). [3H]pirenzepine binding was not significantly altered in either disorder in any cortical region examined (p>0.05).
Limitations
9 bipolar disorder, 9 major depressive disorder and 19 control subjects were used in the study.
Conclusion
Our data is consistent with previously published data implicating a role for CHRM2 receptors in the pathology of bipolar and major depressive disorder. The demonstration of a novel association between decreased CHRM3 receptor expression and bipolar disorder suggests bipolar and major depressive disorder differ in the underlying nature of their cholinergic dysfunction.
doi:10.1016/j.jad.2008.11.015
PMCID: PMC2724602  PMID: 19103464
Bipolar Disorder; Depression; Muscarinic Receptors; Post-Mortem; Frontal Cortex
10.  Hereditary diffuse leucoencephalopathy with spheroids 
doi:10.1136/jnnp.74.9.1345
PMCID: PMC1738687  PMID: 12933955
11.  The management of orbital cysts associated with congenital microphthalmos and anophthalmos 
Aims: To study the management of the orbital cysts present in a group of patients with anophthalmos and microphthalmos.
Methods: A retrospective study of 34 patients (40 orbits) treated for orbital cyst associated with microphthalmos and anophthalmos.
Results: The two largest treatment groups comprised 17 orbits (42.5%) where the cyst was removed surgically and 17 orbits (42.5%) where the cyst was retained and conformers were used. The remaining cases comprised two orbits (5%) where the cyst was aspirated initially; two orbits (5%) with large cysts which will need to be excised after further orbital growth; one orbit (2.5%) in which a silicone expander was used initially, and one orbit (2.5%) in which a mildly microphthalmic eye had some vision and was monitored but required no surgery.
Conclusion: In this study 33 out of 34 patients had a good cosmetic result which illustrates that the orbital cyst in microphthalmos or anophthalmos performs a useful role in socket expansion and that the majority of patients with this condition can expect a good cosmetic outcome.
PMCID: PMC1771749  PMID: 12812886
orbital cyst; anophthalmos; microphthalmos; orbital surgery
12.  Altered glycosylation of acetylcholinesterase in lumbar cerebrospinal fluid of patients with Alzheimer's disease 
As clinical diagnosis of Alzheimer's disease is only 80%-90% accurate, there is a need to identify biochemical markers of Alzheimer's disease. Previous studies have shown an abnormality in the glycosylation of acetylcholinesterase (AChE) in the CSF collected postmortem from patients with Alzheimer's disease. This abnormality was very specific for Alzheimer's disease, as it was not detected in other illnesses causing dementia. We report here that the glycosylation of AChE is also altered in lumbar CSF collected antemortem. The altered glycosylation was due to increased concentrations of a minor AChE isoform that does not bind to concanavalin A (Con A). Glycosylation of AChE may eventually be of diagnostic value, especially when used in combination with other CSF markers.


doi:10.1136/jnnp.69.5.664
PMCID: PMC1763436  PMID: 11032625
13.  Rhinostomies: an open and shut case? 
The British Journal of Ophthalmology  1999;83(11):1300-1301.
AIMS—To analyse bone fragments from rhinostomies of patients undergoing revisional dacryocystorhinostomy, looking for evidence of new bone formation.
METHODS—14 consecutive patients undergoing secondary lacrimal surgery were included in this study. In each case the existing rhinostomy was enlarged with bone punches, care being taken to use the punches with the jaws cutting perpendicularly to the edge of the rhinostomy, to allow accurate orientation of the specimens. The fragments were examined histologically for evidence of new bone formation.
RESULTS—Histological sections showed fragments of bone with variable fibrosis at the edge of the rhinostomy. There was evidence of only very little new bone formation.
CONCLUSION—This study has clearly shown that, at the edge of a rhinostomy, healing is predominantly by fibrosis and there is only very limited new bone formation.


PMCID: PMC1722857  PMID: 10535862
14.  5-fluorouracil steady state pharmacokinetics and outcome in patients receiving protracted venous infusion for advanced colorectal cancer 
British Journal of Cancer  2001;84(5):600-603.
PVI 5FU gives increased response rates and reduced toxicity when compared to bolus 5FU (J Clin Oncol 1989, 425–432). PVI 5FU administration was reported to give highly variable (>1000-fold) plasma 5FU concentrations at steady state (FU Css) which correlated with toxicity (Ann Oncol 1996, 47–53); but only 19 patients were studied. Therefore, we performed a study of PVI 5FU in 61 patients with advanced colorectal cancer to assess the variability (inter- and intra-subject) in 5FU Css associated with PVI 5FU (300 mg m−2day−1) and to attempt to correlate pharmacodynamic end-points (anti-tumour activity, toxicity) with 5FU Css as a prelude to ‘exposure-guided’ 5FU administration. All 5FU sampling was performed between 10 am and noon. PVI 5FU administration continued to 26 weeks in patients with disease improvement or stabilization. The response rate was 26% (33% stable disease) and median survival was 11 months. Hand–foot syndrome was the most common dose limiting toxicity. Variability in 5FU 300 Css was considerably less than previously reported; 94 ± 25 ng ml−1(CV = 27%). No relationships were demonstrated between subject mean 5FU 300 Css and PD end-points such as response, mucositis, diarrhoea and hand–foot syndrome. The lack of correlation suggests that measurement of 5FU concentrations should not be used to individualize dosing in patients receiving PVI 5FU for advanced colorectal cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com
doi:10.1054/bjoc.2000.1664
PMCID: PMC2363784  PMID: 11237378
protracted infusion 5FU; 5FU pharmacokinetics; colorectal cancer
15.  Pharmacokinetics of EMLA cream 5% application to oral mucosa. 
Anesthesia Progress  1997;44(1):32-37.
Plasma concentrations of lidocaine and prilocaine were measured following the application of a 5% eutectic mixture of local anesthetics (EMLA) topical anesthetic cream to the oral mucosa of twelve subjects. For each subject, a total of 8 g of EMLA was occluded to 18 cm2 of buccal mucosa for 30 min. Analysis was carried out by high-pressure liquid chromatography, and results showed peak concentrations at 40 min for lidocaine and prilocaine. The maximum concentration measured in any subject was 418 ng/ml for lidocaine and 223 ng/ml for prilocaine, well below known toxic levels. No adverse local effects were observed from a 30-min application of EMLA. A follow-up pilot study assessing the clinical efficacy of EMLA for achieving sufficient analgesia for restorative procedures showed that the cream was successful in 75% of subjects tested.
PMCID: PMC2148857  PMID: 9481979
16.  Ocular superglue injury. 
OBJECTIVE: To determine the incidence of ocular injuries associated with superglue. METHODS: A retrospective review of patients attending an accident and emergency department over a 12 month period with ocular superglue injuries. RESULTS: 14 patients who suffered ocular injuries due to superglue were identified. No patients had long term complications from their injury. Management is discussed. CONCLUSIONS: Superglue eye injuries do not appear to cause long term morbidity.
PMCID: PMC1342844  PMID: 9023623
19.  Vaccine potential of a herpes simplex virus type 1 mutant with an essential glycoprotein deleted. 
Journal of Virology  1994;68(2):927-932.
Several approaches to the production of vaccines to human herpesviruses have been proposed. Subunit vaccines, subunits delivered by live vectors, and rationally attenuated vaccines have all been shown to be efficacious in animal models but suffer from uncertainties as to the roles of individual genes involved in pathogenesis and the most relevant components of the immune response required for protection in humans and the target antigens involved. With these problems in mind, we examined the vaccine potential of a fully disabled herpes simplex virus type 1 mutant that is capable of only a single round of replication, since a virus of this type should induce the full spectrum of immune responses but has no pathogenic potential. A virus has been described which lacks essential glycoprotein H (gH) and can be propagated in a cell line which supplies gH in trans (A. Forrester, H. Farrell, G. Wilkinson, J. Kaye, N. Davis-Poynter, and T. Minson, J. Virol. 66:341-348, 1992). Infection of normal cells with this mutant is indistinguishable from a wild-type infection, except that the resulting progeny are gH negative and noninfectious: the virus is self-limiting. Infection of mice by the ear pinna route was similarly self-limiting in that input infectivity decreased rapidly at the inoculation site and no infectivity was detected in sensory ganglia. Animals given a wide range of doses of the gH-negative mutant produced both humoral and T-cell responses to herpes simplex virus type 1 and proved solidly resistant to challenge with a high dose of wild-type virus. The gH-negative mutant is presumably capable of establishing a latent infection, but since no infectious virus was detected in numerous attempts to reactivate the mutant, the risk of a pathogenic outcome is minimal.
Images
PMCID: PMC236530  PMID: 8289395
20.  Production and characterisation of a monoclonal antibody to human papillomavirus type 16 using recombinant vaccinia virus. 
Journal of Clinical Pathology  1990;43(6):488-492.
A monoclonal antibody was raised against the major capsid protein L1 of human papillomavirus type 16, using a recombinant vaccinia virus that expresses the L1 protein, as a target for screening. This antibody, designated CAMVIR-1, reacted with a 56 kilodalton protein in cells infected with L1-vaccinia virus, and the protein was present in a predominantly nuclear location. The antibody also detects the HPV-16 L1 antigen in formalin fixed, paraffin wax embedded biopsy specimens and on routine cervical smears. The antibody reacts strongly and consistently with biopsy specimens containing HPV-16 or HPV-33, but very weak reactions were occasionally observed with biopsy specimens or smears containing HPV-6 or HPV-11. The potential advantages of using a vaccinia recombinant are (i) the target protein is synthesised in a eukoryotic cell so that its "processing" and location are normal; (ii) cells infected with vaccinia recombinants can be subjected to various fixing procedures similar to those used for routine clinical material. This greatly increases the probability that an identified antibody will be useful in a clinical setting.
Images
PMCID: PMC502503  PMID: 2166093
21.  The 5' untranslated region of the I factor, a long interspersed nuclear element-like retrotransposon of Drosophila melanogaster, contains an internal promoter and sequences that regulate expression. 
Molecular and Cellular Biology  1993;13(2):1042-1050.
The I-R system of hybrid dysgenesis in Drosophila melanogaster is controlled by a long interspersed nuclear element-like retroposon, the I factor. Transposition of the I factor occurs at a high frequency only in the ovaries of females produced by crossing males of inducer strains that contain functional I factors with females of reactive strains that lack them. In this study, the 5' untranslated region of the I factor was joined to the chloramphenicol acetyltransferase gene, and activity was assayed in transfected D. melanogaster tissue culture cells and transformed flies. The results have identified a promoter that lies within the first 186 pb of the I factor. Deletion analysis shows that nucleotides +1 to +40 are sufficient for high promoter activity and accurate transcription initiation. This region contains sequences that are found in a class of RNA polymerase II promoters that lack both a TATA box and CpG-rich motifs. In transformed flies, high levels of expression from nucleotides +1 to +186 are confined to the ovaries of reactive females, suggesting that the promoter is involved in the tissue and cytotype specificity of transposition.
Images
PMCID: PMC358989  PMID: 8380889
24.  Poliomyelitis resurfaced. 
PMCID: PMC1879147  PMID: 188534
25.  Evidence of ambiguous processing and selective degradation in the noncapsid proteins of rhinovirus 1A. 
Journal of Virology  1976;19(3):903-914.
Pulse-chase kinetics and extensive pactamycin mapping studies show that the translation of rhinovirus 1A proceeds in the order: initiate-P1-S-P2-terminate, where P1 is the precursor to the capsid proteins, S is a stable primary gene product, and P2 is the precursor to a family of noncapsid products. Initial examination of the molar stoichiometry of the families of rhinoviral proteins in infected cells suggested that both the P1 and P2 regions were translated more frequently than the S region. However, we show that this apparent asymmetry in translation is an artifact arising from two phenomena: (i) ambiguous cleavage sites which result in two alternative products from the S region, having apparent molecular weights of 47,000 and 38,000, and (ii) several fates for the P2 precursors, including degradation of 35 to 45% of the P2 family to small unidentifiable products. Another artifact, a time-dependent shift in the pactamycin mapping position of polypeptide r-39, was traced to a selective inhibition of the rate of cleavage of its precursor (peak 76). The processing rate of the capsid precursor (peak 92) was not retarded by pactamycin.
PMCID: PMC354931  PMID: 184304

Results 1-25 (32)