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D L Roberts

Publications and source records attributed to D L Roberts.

At least 19 recordsLinked to original sources
PubMed2004

Variations in registration of skin cancer in the United Kingdom.

Cancer registries are used to compare incidences between regions, plan for service provision, and to assess the impact of health interventions. Significant variation in data capture for skin cancers and reporting of results was evident between regional cancer registries in the UK when assessed in 1991. Using a postal questionnaire we sought to document methods of recording skin cancer incidence in the UK in 2000, and to assess if practice has changed from 1991. All UK cancer registries were asked for details of their method of skin cancer case registration and latest available incidence figures. Methodology was assessed against recently implemented national standards. All registries responded to the survey. Sources of data were more uniform than was the case 9 years ago. All registries except one attained national standards for basal cell carcinoma data collection, but only half of the registries attained standards for squamous cell carcinoma. Ten of the 12 correctly recorded numbers of malignant melanomas, but three still failed to record the Breslow thickness or Clarke's level. Wide variation is evident in the recorded incidences for each of the malignancies, and the efficiency at which figures are made available. Thus, although there has been improvement since 1991, variability still exists between UK registries in methods of data capture, the data recorded, and efficiency of data processing in skin cancer registration.

Basal Cell Carcinoma↗
PubMed2002

Pseudopollen and food-hair diversity in Polystachya Hook. (Orchidaceae).

Labellar food-hairs in Polystachya Hook. exhibit considerable morphological diversity. The commonest type of trichome is uniseriate, two to four-celled, with a clavate or subclavate terminal cell. This type occurs amongst representatives of most sections examined. Other trichomes are bristle-like with tapering or fusiform terminal cells, whereas representatives of section Polystachya have uniseriate, moniliform trichomes that fragment with the formation of rounded or elliptical component cells. Most contain protein and, while some contain starch, lipid is invariably absent. The presence of particular types of labellar trichomes does not coincide with variations in vegetative morphology. Thus, current taxonomic treatment of the genus indicates that trichome types, with perhaps the sole exception of moniliform, pseudopollen-forming hairs found in section Polystachya only, have limited taxonomic value. However, the remarkable similarity between pseudopollen-forming hairs of Polystachya and those of the Neotropical genus Maxillaria in terms of morphology, cellular dimensions and food content indicates that pseudopollen may have arisen several times and evolved in response to similar pollinator pressures.

Cell Surface Extensions↗
PubMed2001

The inhibitor of apoptosis protein-binding domain of Smac is not essential for its proapoptotic activity.

Smac/DIABLO, a recently identified inhibitor of apoptosis protein (IAP)-binding protein, is released from the mitochondria during apoptosis and reportedly potentiates apoptosis by relieving the inhibition of IAPs on caspases. We now describe the molecular characterization of Smac beta, an alternatively spliced form of Smac, which lacks the mitochondrial-targeting sequence found in Smac and has a cortical distribution in both human embryonic kidney 293 and breast epithelial tumor MCF-7 cells. Smac beta, which binds IAPs in vitro, does not bind IAPs in intact cells due to cellular processing and removal of its NH(2)-terminal IAP-binding domain. Despite its inability to interact with IAPs in cells, processed Smac beta is proapoptotic, as demonstrated by its ability to potentiate apoptosis induced by both death receptor and chemical stimuli. Furthermore, expression of a NH(2)-terminally truncated Smac mutant (Delta75), which lacks the entire IAP-interacting domain, potentiates apoptosis to the same extent as Smac and Smac beta. Our data support the hypothesis that the main proapoptotic function of Smac and Smac beta is due to a mechanism other than IAP binding.

Amino Acid Sequence↗
PubMed2001

Caspase-3 cleaves Apaf-1 into an approximately 30 kDa fragment that associates with an inappropriately oligomerized and biologically inactive approximately 1.4 MDa apoptosome complex.

Cytochrome c and dATP/ATP induce oligomerization of Apaf-1 into two distinct apoptosome complexes: an approximately 700 kDa complex, which recruits and activates caspases-9, -3 and -7, and an approximately 1.4 MDa complex, which recruits and processes caspase-9, but does not efficiently activate effector caspases. While searching for potential inhibitors of the approximately 1.4 MDa apoptosome complex, we observed an approximately 30 kDa Apaf-1 immunoreactive fragment that was associated exclusively with the inactive complex. We subsequently determined that caspase-3 cleaved Apaf-1 within its CED-4 domain (SVTD(271) downward arrowS) in both dATP-activated lysates and apoptotic cells to form a prominent approximately 30 kDa (p30) N-terminal fragment. Purified recombinant Apaf-1 p30 fragment weakly inhibited dATP-dependent activation of caspase-3 in vitro. However, more importantly, prevention of endogenous formation of the p30 fragment did not stimulate latent effector caspase processing activity in the large complex. Similarly, the possibility that XIAP, an inhibitor of apoptosis protein (IAP), was responsible for the inactivity of the approximately 1.4 MDa complex was excluded as immunodepletion of this caspase inhibitor failed to relieve the inhibition. However, selective proteolytic digestion of the approximately 1.4 MDa and approximately 700 kDa complexes showed that Apaf-1 was present in conformationally distinct forms in these two complexes. Therefore, the inability of the approximately 1.4 MDa apoptosome complex to process effector caspases most likely results from inappropriately folded or oligomerized Apaf-1.

Amino Acid Sequence↗
PubMed2001

Audit of a melanoma screening day in the U.K.: clinical results, participant satisfaction and perceived value.

BACKGROUND: The incidence of cutaneous malignant melanoma (MM) has risen significantly over the last 50 years in caucasian populations. Mortality is related to the Breslow thickness of the lesion, and early detection followed by complete surgical excision is crucial to reducing this. Skin screening events have been advocated as a means of detecting greater numbers of MMs in the earlier and thinner stages. OBJECTIVES: To assess the feasibility and effectiveness of this approach in the U.K. METHODS: The Department of Dermatology, Singleton Hospital, Swansea, U.K. offered a 1-day melanoma screening event in summer 1998 at which 832 consecutive individuals were seen. A postal questionnaire 1 year after the event audited participant perceived value and satisfaction. RESULTS: Three MMs were identified (yield 1 : 277), all < 0.75 mm in thickness. Despite high participant satisfaction and perceived value, the pick-up rate of malignancy was significantly lower than at rapid access pigmented lesion clinics. CONCLUSIONS: In a country such as the U.K., with comprehensive health coverage and a low incidence of MM, triage for melanoma and referral to specialists by general practitioners may be more cost and time effective.

Adolescent↗
PubMed2001

Malignant melanoma in South Wales: changing trends in presentation (1986-98).

In 1990 we reported the trends in presentation of malignant melanoma (MM) from 1986 to 1988 in a defined population in South Wales. Ten years after this initial study we reassessed the incidence of invasive MM in this defined population over a similar 3 year period. Using the local skin cancer registry we identified 186 cases of MM representing a 74% increase. Age standardization to the world population gives an overall incidence of 11.8 per 100 000 population per annum. This is the highest published standard incidence of MM to date from the UK and certainly one of the highest in Europe. We also have observed a continuing trend for diagnosis of thinner lesions with a better prognosis. Information about mortality for the whole of Wales over the corresponding period is also presented.

Adolescent↗
PubMed2001

Musical hallucinations associated with seizures originating from an intracranial aneurysm.

Hallucinations are defined as sensory phenomena in the absence of external sensory stimuli. Auditory hallucinations have been shown to arise from many different intracranial lesions, but seizures manifesting as musical hallucinations triggered by unruptured intracranial aneurysms are rare. We present a case of persistent, episodic musical hallucinations associated with seizures that led to the discovery of 2 small intracranial aneurysms. Typical electroencephalographic findings for seizure activity were observed but resolved after surgical clipping of the aneurysms. Concomitantly, the patient's hallucinations resolved. The literature on musical hallucinations is reviewed.

Cerebral Angiography↗
PubMed2000

Changing trends in non-melanoma skin cancer in South Wales, 1988-98.

BACKGROUND: In 1988 our department carried out a population-based epidemiological study of non-melanoma skin cancer (NMSC) incidence, over a 6-month period, in West Glamorgan, South Wales. Objectives To reassess the incidence of NMSC in this defined population over a similar 6-month period 10 years after the initial study. METHODS: All cases of basal cell carcinoma and squamous cell carcinoma diagnosed in West Glamorgan are recorded by the local skin cancer registry. All cases for the relevant 6-month period were analysed. RESULTS: Using these figures, we have identified a significant rise in the crude incidence of NMSC from 173.5 10 years ago to 265.4 per 100,000 population per annum. We also applied the world standard population for age to our crude figures, demonstrating a combined male and female world population-corrected rate of 129.9 per 100,000 population. CONCLUSIONS: In our population the crude incidence of NMSC has risen significantly over 10 years. Additionally, the combined male and female world population-corrected rate appears to be the highest published standardized incidence of NMSC to date from any European country.

Adult↗
PubMed2000

Orbital apex lesion as the presenting manifestation of sarcoidosis.

A 32-year-old black woman presented with progressive proptosis, diplopia, and optic disc edema of the right eye. A computed tomography scan of the orbit showed a right retroorbital mass. A gallium scan showed increased radiotracer activity in the right retroorbital region. Biopsy of the mass showed non-caseating granulomas that were compatible with sarcoidosis. The patient was treated with systemic steroids, and the proptosis and diplopia resolved. Seven months later, the patient presented with contralateral optic neuropathy. Neuroimaging showed enlargement of the left optic nerve. The patient again responded to systemic steroid treatment and experienced complete restoration of vision. An orbital apex lesion may be the presenting manifestation of sarcoidosis.

Adult↗
PubMed1999

Crystal structure of Paracoccus denitrificans electron transfer flavoprotein: structural and electrostatic analysis of a conserved flavin binding domain.

The crystal structure of electron transfer flavoprotein (ETF) from Paracoccus denitrificans was determined and refined to an R-factor of 19.3% at 2.6 A resolution. The overall fold is identical to that of the human enzyme, with the exception of a single loop region. Like the human structure, the structure of the P. denitrificans ETF is comprised of three distinct domains, two contributed by the alpha-subunit and the third from the beta-subunit. Close analysis of the structure reveals that the loop containing betaI63 is in part responsible for conferring the high specificity of AMP binding by the ETF protein. Using the sequence and structures of the human and P. denitrificans enzymes as models, a detailed sequence alignment has been constructed for several members of the ETF family, including sequences derived for the putative FixA and FixB proteins. From this alignment, it is evident that in all members of the ETF family the residues located in the immediate vicinity of the FAD cofactor are identical, with the exception of the substitution of serine and leucine residues in the W3A1 ETF protein for the human residues alphaT266 and betaY16, respectively. Mapping of ionic differences between the human and P. denitrificans ETF onto the structure identifies a surface that is electrostatically very similar between the two proteins, thus supporting a previous docking model between human ETF and pig medium-chain acyl-CoA dehydrogenase (MCAD). Analysis of the ionic strength dependence of the electron transfer reaction between either human or P. denitrificans ETF and MCAD demonstrates that the human ETF functions optimally at low ( approximately 10 mequiv) ionic strength, while P. denitrificans ETF is a better electron acceptor at higher (>75 mequiv) ionic strength. This suggests that the electrostatic surface potential of the two proteins is very different and is consistent with the difference in isoelectric points between the proteins. Analysis of the electrostatic potentials of the human and P. denitrificans ETFs reveals that the P. denitrificans ETF is more negatively charged. This excess negative charge may contribute to the difference in redox potentials between the two ETF flavoproteins and suggests an explanation for the opposing ionic strength dependencies for the reaction of MCAD with the two ETFs. Furthermore, by analysis of a model of the previously described human-P. denitrificans chimeric ETF protein, it is possible to identify one region of ETF that participates in docking with ETF-ubiquinone oxidoreductase, the physiological electron acceptor for ETF.

Adenosine Monophosphate↗
PubMed1999

Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression.

The efficacy of nefazodone in prevention of relapse of depression was evaluated in a 36-week double-blind, placebo-substitution, continuation treatment trial. After 16 weeks of acute, single-blind treatment with nefazodone, 131 patients responding to treatment and in stable remission were randomized in a 36-week double-blind trial to either nefazodone (n = 65) or placebo (n = 66). Patients were defined as having relapsed if they had a total score > or = 18 on the 17-item Hamilton Depression Scale on two consecutive visits or if they discontinued treatment for lack of efficacy. Relapse rates were significantly lower for patients randomized to continued nefazodone treatment than for patients switched to placebo. Kaplan-Meier estimates of relapse rates 9 months (36 weeks) after the end of acute treatment were 1.8% for nefazodone versus 18.3% for placebo (P = 0.009) by the Hamilton Depression Scale and 17.3% versus 32.8% (P = 0.028) by discontinuation for lack of efficacy. The mean modal dose of nefazodone was 412 mg/day at study endpoint. These results demonstrate the clinical effectiveness of up to 1 year's treatment (16 weeks acute and 36 weeks continuation) with nefazodone in depressed patients. Long-term efficacy of nefazodone was accompanied by a good safety profile without any weight gain and with minimal symptoms of withdrawal upon abrupt discontinuation of treatment.

Adult↗
PubMed1998

Molecular basis of lysosomal enzyme recognition: three-dimensional structure of the cation-dependent mannose 6-phosphate receptor.

Targeting of newly synthesized lysosomal hydrolases to the lysosome is mediated by the cation-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/CI-MPR). The two receptors, which share sequence similarities, constitute the P-type family of animal lectins. We now report the three-dimensional structure of a glycosylation-deficient, yet fully functional form of the extracytoplasmic domain of the bovine CD-MPR (residues 3-154) complexed with mannose 6-phosphate at 1.8 A resolution. The extracytoplasmic domain of the CD-MPR crystallizes as a dimer, and each monomer folds into a nine-stranded flattened beta barrel, which bears a striking resemblance to avidin. The distance of 40 A between the two ligand-binding sites of the dimer provides a structural basis for the observed differences in binding affinity exhibited by the CD-MPR toward various lysosomal enzymes.

Amino Acid Sequence↗
PubMed1998

A double-blind, placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression.

BACKGROUND: There are few published placebo-controlled clinical trials demonstrating the efficacy of the newer antidepressants in markedly or severely depressed hospitalized patients. This study demonstrates the efficacy of nefazodone compared with placebo in the treatment of patients hospitalized for major depression. METHOD: Nefazodone and placebo treatment were compared in a 6-week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression (without psychosis) at 2 study centers. Efficacy was evaluated using standard psychiatric rating scales, and patients were monitored for safety. RESULTS: Nefazodone treatment resulted in a significant reduction (p < .01) of the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score compared with placebo from the end of the first treatment week through the end of the study (-12.2 nefazodone vs. -7.7 placebo). At the end of the trial, significantly more nefazodone-treated patients (50%) than placebo-treated patients (29%) had responded, as indicated by their Clinical Global Impressions-Improvement score (p = .021) or by a > or = 50% reduction in their HAM-D-17 scores (p = .017). Significantly more patients treated with nefazodone (36%) than placebo-treated patients (14%) had a HAM-D-17 score < or = 10 at the end of treatment (p = .004). Significant treatment differences (p < .01) in favor of nefazodone were also seen in the Montgomery-Asberg Depression Rating Scale; the HAM-D retardation, anxiety, and sleep disturbance factors; and HAM-D item 1 (depressed mood). Patients with dysthymia in addition to major depression also showed significant improvement (p < .05) when treated with nefazodone, with significant differences in response rates seen as early as week 2 and through the end of the trial. The mean nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of treatment. Nefazodone was well tolerated, and the number of patients discontinuing owing to adverse events was small, with no significant safety issues noted in either treatment group. Fewer nefazodone-treated than placebo-treated patients discontinued owing to lack of efficacy. CONCLUSION: Nefazodone was superior to placebo in the treatment of marked to severe major depression in patients requiring hospitalization. The clinical benefit of nefazodone was evident as early as the first week of treatment as judged by several measures of efficacy, with significant differences from placebo sustained throughout the trial.

Adult↗