A mutation (2314delG) in the Usher syndrome type IIA gene: high prevalence and phenotypic variation.
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Adolescent↗
Biomedical subjects
C Hope
Publications and source records attributed to C Hope.
Mutations in the myosin VIIA gene cause a wide phenotypic spectrum, including atypical Usher syndrome.
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Adolescent↗
Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum.
Human pancreatic cancers over-express the epidermal growth factor receptor (EGF-R) and all 5 known ligands of the EGF family, including EGF, transforming growth factor-alpha (TGF-alpha), amphiregulin, betacellulin and heparin-binding EGF-like growth factor (HB-EGF). The aim of the present study was to confirm the presence of EGF-R-dependent autocrine loops in a human pancreatic cancer cell line and to explore the possibility that interrupting EGF-R activation by introducing a truncated receptor abrogates pancreatic cancer cell growth. The anchorage-independent growth of PANC-1 human pancreatic cancer cells, previously shown to express TGF-alpha, was inhibited by specific anti TGF-alpha antibodies. PANC-1 cells were then either transfected with an expression plasmid encoding a kinase-deficient EGF-R cDNA (HER653) or infected with the same EGF-R cDNA using a retroviral vector. Multiple transfected and infected clones co-expressed the truncated EGF-R and endogenous EGF-R as revealed by Northern blot analysis and immunoblots. In these clones, there was a marked attenuation in EGF- and TGF-alpha-mediated EGF-R tyrosine phosphorylation and c-fos induction. There was also a significant decrease in colony formation in soft agar by comparison with control cells and a significant increase in the effect of the growth-inhibitory effect of the alkylating agent cisplatinum in these clones. Our observations indicate that dominant negative inhibition of EGF-R may have therapeutic potential in pancreatic cancer.
Antineoplastic Agents↗
Analgesic effect of extracorporeal shock-wave therapy on chronic tennis elbow.
We report a controlled, prospective study to investigate the effect of treatment by low-energy extracorporeal shock waves on pain in tennis elbow. We assigned at random 100 patients who had had symptoms for more than 12 months to two groups to receive low-energy shock-wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm2 and group II, the control group, 30 impulses. The patients were reviewed after 3, 6 and 24 weeks. There was significant alleviation of pain and improvement of function after treatment in group I in which there was a good or excellent outcome in 48% and an acceptable result in 42% at the final review, compared with 6% and 24%, respectively, in group II.
Adult↗
A variant epidermal growth factor receptor exhibits altered type alpha transforming growth factor binding and transmembrane signaling.
Epidermal growth factor (EGF) and type alpha transforming growth factor (TGF-alpha) bind to a specific region in subdomain III of the extracellular portion of the EGF receptor (EGFR). Binding leads to receptor dimerization, auto-and transphosphorylation on intracellular tyrosine residues, and activation of signal transduction pathways. We compared the binding and biological actions of EGF and TGF-alpha in Chinese hamster ovary (CHO) cells expressing either wild-type human EGFR (HER497R) or a variant EGFR that has an arginine-to-lysine substitution in the extracellular domain at codon 497 (HER497K) within subdomain IV of EGFR. Both receptors exhibited two orders of binding sites with radioiodinated EGF (125I-EGF). Similar results were obtained with 125I-TGF-alpha in cells expressing HER497R. In contrast, only one order of low-affinity binding sites was seen with 125I-TGF-alpha in the case of HER497K. Although EGF and TGF-alpha enhanced tyrosine phosphorylation of both receptors, CHO cells expressing HER497K exhibited an attenuated growth response to EGF and TGF-alpha and a reduced induction of the protooncogenes FOS, JUN, and MYC. Moreover, high concentrations of TGF-alpha (5 nM) inhibited growth in these cells but not in cells expressing HER497R. These findings indicate that a region in subdomain IV of EGFR regulates signal transduction across the cell membrane and selectively modulates that binding characteristics of TGF-alpha.
Animals↗
Community photoscreening of six to nine month old infants for amblyopiogenic risk factors.
Photorefraction (PR) is gaining acceptance as potentially the most effective objective screening technique for amblyopia risk factors in the preverbal child. This study determined the validity and feasibility of using the Auckland eccentric photorefractor in the detection of amblyopiogenic factors in six to nine month old infants in an established community-based vision screening program. Photographs were analysed and compared to results of clinical examination including cycloplegic refraction. Amblyopia risk factors were present in 7.2% of the infants clinically examined. Analysis only of readable photographs in children who were also clinically examined, gave sensitivities ranging from 71% to 79%, and specificities ranging from 81% to 86%. Inclusion in the analysis of photo-failures lowered sensitivity figures to 56% to 61%, and specificity to 63% to 70%. Photofailures were predominantly due to poor operator technique. Calculation of kappa scores indicated fair observer reliability. In conclusion, PR could provide a feasible and sufficiently reliable screening technique in the infant, but requires adequate training and auditing of screening personnel performance for optimum effectiveness.
Amblyopia↗
Photoscreening to detect potential amblyopia.
Photoscreening to detect amblyopiogenic conditions is particularly applicable for the child under three years of age because conventional testing is difficult. We have designed an eccentric photoscreener that is inexpensive, easily used and requires only one diagnostic photograph. Some 231 infants and children were refracted and photoscreened and results compared in a blind study. Compliance was good and all cases of strabismus, amblyopia, and amblyopiogenic conditions were diagnosed.
Adolescent↗
Random dot stereogram E in vision screening of children.
The random dot stereogram E (RDE) has been shown to be a simple and effective test for the detection of binocular abnormalities and defective visual acuity in children. We determined the validity of the RDE as a screening test for reduced visual acuity, amblyopia and strabismus in two separate populations of children. A nonselective group of 100 school children (aged 5 to 15 years) who presented consecutively to the ophthalmology department at Auckland Public Hospital were tested with the RDE. All cases of amblyopia and strabismus were detected by the RDE. Similar screening with the RDE test of 168 preschool children (aged three to four years) in the community resulted in an unacceptably high over-referral rate. The test was unreliable in the preschool age group because of difficulty in distinguishing between test failure and non-cooperation with the test. The low positive predictive value of the test in the younger age group suggests the test to be unsuitable for preschool vision screening.
Adolescent↗
A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease.
Vaccinations with amyloid-beta peptide (A beta) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease. To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A beta vaccination in a different transgenic model for Alzheimer's disease in which mice develop learning deficits as amyloid accumulates. Here we show that vaccination with A beta protects transgenic mice from the learning and age-related memory deficits that normally occur in this mouse model for Alzheimer's disease. During testing for potential deleterious effects of the vaccine, all mice performed superbly on the radial-arm water-maze test of working memory. Later, at an age when untreated transgenic mice show memory deficits, the A beta-vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The A beta-vaccinated mice also had a partial reduction in amyloid burden at the end of the study. This therapeutic approach may thus prevent and, possibly, treat Alzheimer's dementia.
Aging↗