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W C Smith

Publications and source records attributed to W C Smith.

At least 55 records · Page 3Linked to original sources
PubMed1999

The origins of primitive blood in Xenopus: implications for axial patterning.

The marginal zone in Xenopus laevis is proposed to be patterned with dorsal mesoderm situated near the upper blastoporal lip and ventral mesoderm near the lower blastoporal lip. We determined the origins of the ventralmost mesoderm, primitive blood, and show it arises from all vegetal blastomeres at the 32-cell stage, including blastomere C1, a progenitor of Spemann's organizer. This demonstrates that cells located at the upper blastoporal lip become ventral mesoderm, not solely dorsal mesoderm as previously believed. Reassessment of extant fate maps shows dorsal mesoderm and dorsal endoderm descend from the animal region of the marginal zone, whereas ventral mesoderm descends from the vegetal region of the marginal zone, and ventral endoderm descends from cells located vegetal of the bottle cells. Thus, the orientation of the dorsal-ventral axis of the mesoderm and endoderm is rotated 90( degrees) from its current portrayal in fate maps. This reassessment leads us to propose revisions in the nomenclature of the marginal zone and the orientation of the axes in pre-gastrula Xenopus embryos.

Animals↗
PubMed1999

Nerve function impairment in leprosy: design, methodology, and intake status of a prospective cohort study of 2664 new leprosy cases in Bangladesh (The Bangladesh Acute Nerve Damage Study).

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study designed to investigate epidemiological, diagnostic, therapeutic and operational aspects of acute nerve function impairment in leprosy. The study is based at a single centre in Bangladesh, in an area with a high prevalence of leprosy. The centre, Danish Bangladesh Leprosy Mission, has a well-established vertical leprosy control programme. In this paper, the study design and methodology are described, together with definitions of nerve function impairment (NFI) used in this and subsequent papers. The study recruited 2664 new leprosy cases in a 12-month period. The male:female ratio is 1.25:1, and 17.61% of the cohort are under 15 years of age. In all, 83.33% of the cohort are paucibacillary (PB), and 16.67% multibacillary (MB). However, the MB rate amongst males is 19.72%, and amongst females is 12.85%, despite an equal period of delay to diagnosis. 55% of patients presented for treatment within 12 months of developing symptoms 6.12% of the total number of cases were smear positive, and 36.71% of the MB cases were smear positive. 9.61% of the total number of cases were graded as having World Health Organisation (WHO) disability grade 1, and 5.97% had grade 2. Amongst MB cases, 27.48% had WHO grade 1 disability present, and 18.24% had grade 2 present, compared with 6.04% and 3.51%, respectively, amongst PB cases. A total of 11.90% of the cohort had sensory NFI of any kind, and 7.39% had motor NFI. Ninety patients presented with NFI needing treatment (3.38%), and of these, 61 (67.78%) had silent NFI. MB patients had a prevalence of reaction/NFI needing treatment nearly 7 times higher than PB cases (15.32% amongst MB; 2.30% amongst PB), and males nearly double that of females (5.67% amongst males, 2.96% amongst females). The most commonly affected nerve by function impairment was the posterior tibial (sensory) with 6.46% of nerves affected (9.38% of patients), followed by the ulnar nerve with 3.23% of nerves impaired (5.56% of patients). Future research and publications, building on this foundation, will focus on the following areas: the incidence of NFI and reactive events, the risk factors for developing NFI, and the response to treatment of patients developing acute NFI.

Bangladesh↗
PubMed1999

Future scope and expectations: why, when, and how LECs should continue.

There is a strong case to continue to use LEC approaches, as they are a comprehensive and cost effective means of delivering the key elements of leprosy control. LECs should be conducted when there is evidence of large numbers of hidden cases. Probably a minimum of two LECs is required but where large number of new cases continue to be detected they could be run on an annual basis. The methodology of LECs needs to be improved through experience, evaluation and from LECs conducted elsewhere; feedback from the community is also important. There is room to improve all aspects of LECs: planning, training, education, diagnosis and treatment completion.

Forecasting↗
PubMed1999

Disease and disease control. International Leprosy Congress, Beijing, 7-12 September 1998. Workshop report.

Four workshops were conducted during the congress under the disease control theme. The workshops were on the issues of defining disease and antibacterial therapy, early case detection, sustaining leprosy control in low endemic situations, and the prevention of disability. These workshops spanned the spectrum of disease and its consequences through from early detection, the definition of disease to the prevention of disability. All of these topics being important contemporary issues challenging leprosy control programmes world wide. Despite the broad spectrum of the topics it was interesting to see that a number of important themes emerged which were common to all topics. It is possible to identify five major themes arising from the output of the workshops which are now described below. Each of the workshops adopted broad and comprehensive approaches to their topic. In the past, there has been narrowness in defining disease in terms of the need for chemotherapy. The approach taken in the workshop now is for a much more comprehensive approach looking at all the consequences of the disease process rather than the requirement for antibacterial chemotherapy. Similarly broad approaches were taken to low endemic situations, considering comprehensive approaches which are inclusive rather than exclusive. Disability prevention also continues this same theme of comprehensive approaches based on multidisciplinary involvement in prevention of the consequences of the disease process. The second major theme to be identified in the output of the workshops was the importance of relevance to patients and people affected by leprosy. It is no longer adequate to view programmes in terms of their acceptance to those running the programmes. Control programmes must be acceptable to the people they are designed to benefit. This even impacts on definitions of disease in terms of what matters to patients rather than only restricting this to disease pathology. Similarly, approaches to disability prevention are not merely about measurement of impairments due to nerve function deficit but rather consider the abilities and functions which are most important to the individuals affected. The third theme which spans all of the workshops is the need to develop partnerships with others in addressing the challenges of leprosy today. Each workshop identified important groups with which partnerships need to be developed included local patient groups, voluntary associations and primary health care services. All of these have a role to play, from early case detection right through to the prevention of disability and the sustaining of control under low endemic situations. The fourth important theme is sustainability of programmes which need to be developed for the long term benefit of those affected by disease rather than short term goals. Again, this impacts an area such as case detection methods which need to be sustained in the long term. Approaches such as intensive case detection through mass survey are not sustainable given changes to the patterns of disease, whereas involvement of communities and community participation in the process of early case detection is a much more sustainable approach. This is important, as programmes attain low endemic status and is also important in preventing disabilities where the progressive nature of secondary impairments following primary impairments may be lifelong. The final theme is that of the importance of training, as each area is recommending new approaches to be taken and for new people to be involved in leprosy programmes. The implications are that those to be involved need to be trained and that the training requirements will be different from those of the last ten years. Training programmes will need to adapt to a wider range of individuals and groups being involved in programmes and to much more comprehensive approaches. These implications for training are profound and training centres and training programmes rapidly

China↗
PubMed1998

A myosin III from Limulus eyes is a clock-regulated phosphoprotein.

The lateral eyes of the horseshoe crab Limulus polyphemus undergo dramatic daily changes in structure and function that lead to enhanced retinal sensitivity and responsiveness to light at night. These changes are controlled by a circadian neural input that alters photoreceptor and pigment cell shape, pigment migration, and phototransduction. Clock input to the eyes also regulates photomechanical movements within photoreceptors, including membrane shedding. The biochemical mechanisms underlying these diverse effects of the clock on the retina are unknown, but a major biochemical consequence of activating clock input to the eyes is a rise in the concentration of cAMP in photoreceptors and the phosphorylation of a 122 kDa visual system-specific protein. We have cloned and sequenced cDNA encoding the clock-regulated 122 kDa phosphoprotein and show here that it is a new member of the myosin III family. We report that Limulus myosin III is similar to other unconventional myosins in that it binds to calmodulin in the absence of Ca2+; it is novel in that it is phosphorylated within its myosin globular head, probably by cAMP-dependent protein kinase. The protein is present throughout the photoreceptor, including the region occupied by the photosensitive rhabdom. We propose that the phosphorylation of Limulus myosin III is involved in one or more of the structural and functional changes that occur in Limulus eyes in response to clock input.

Amino Acid Sequence↗
PubMed1998

Rhodopsins from three frog and toad species: sequences and functional comparisons.

The frequency of thermal 'dark events' in the membrane current of rhodopsin rods of the bullfrog, Rana catesbeiana, is considerably lower than observed in rods of two toad species, even though all three rhodopsins have approximately the same absorbance characteristics. In order to map amino acid substitutions possibly associated with thermal stability in the genus Rana, the cDNA's coding for the rhodopsins of Bufo bufo, B. marinus and R. temporaria were sequenced and the conceptually translated protein sequences aligned to the previously sequenced rhodopsins of R. catesbeiana, R. pipiens and Xenopus laevis. Across the six anuran species studied, there are sixteen non-conserved substitutions and six changes that include gain or loss of a hydroxyl group. Serine or threonine at position 220 is unique to the three Rana species, phenylalanine at position 270 is unique to all three Ranas and to X. laevis, and phenylalanine at position 274 is unique to both species of the genus Bufo. This investigation produces a list of substitutions that are candidates for future studies of thermal stability. In addition, a number of amino acids are identified that apparently do not influence absorbance characteristics, at least not cumulatively.

Amino Acid Sequence↗
PubMed1998

Two dogmas of conceptual empiricism: implications for hybrid models of the structure of knowledge.

Concepts seem to consist of both an associative component based on tabulations of feature typicality and similarity judgments and an explanatory component based on rules and causal principles. However, there is much controversy about how each component functions in concept acquisition and use. Here we consider two assumptions, or dogmas, that embody this controversy and underlie much of the current cognitive science research on concepts. Dogma 1: Novel information is first processed via similarity judgments and only later is influenced by explanatory components. Dogma 2: Children initially have only a similarity-based component for learning concepts; the explanatory component develops on the foundation of this earlier component. We present both empirical and theoretical arguments that these dogmas are unfounded, particularly with respect to real world concepts; we contend that the dogmas arise from a particular species of empiricism that inhibits progress in the study of conceptual structure; and finally, we advocate the retention of a hybrid model of the structure of knowledge despite our rejection of these dogmas.

Association Learning↗
PubMed1998

Conceptual and statistical issues in the validation of analytic dilution assays for pharmaceutical applications.

The discovery, research, and development of a pharmaceutical product relies on the availability of validated assays for assessing product characteristics and drug effects in vivo and in vitro. Development of a validated assay is a multifaceted activity that provides many interesting challenges for bioanalytical chemists and statisticians. In this paper, the similarity condition for fundamental validity of an analytic dilution assay is reviewed as a basic concept underlying the validation of assays for pharmaceutical applications. The distinction between the validity and the acceptability of an assay is considered in terms of the characteristics evaluated during four stages of validation. Recent guidelines on the validation of analytical procedures published by the U.S. Food and Drug Administration are appraised from a statistical perspective, and statistical issues in the validation process are discussed.

Chemistry, Pharmaceutical↗
PubMed1998

Leprosy transmission and mucosal immunity: towards eradication?

The declining prevalence of leprosy has not been matched by a declining incidence. Widespread adoption of multiple drug therapy (MDT) in closely monitored control programmes has not prevented transmission of Mycobacterium leprae. Despite the rarity of lepromatous patients, most of those living in endemic areas have immunological evidence of exposure to M. leprae. This paradox could be explained if, for many such individuals, infection was transient, did not result in disease development, but did allow the transmission of infection to other individuals. There is increasing evidence from nasal PCR studies that such sub-clinical transmission may exist and that mucosal immune responses to M. leprae may develop during resolution of initial infection. Sub-clinical infection appears to occur in clusters and may require close contact over a prolonged period for optimal transmission. Control of transmission may be feasible through identification and treatment of individuals within infection clusters, allowing progress towards the eradication of leprosy.

Humans↗
PubMed1998

Computed axial tomography of the porcine nasal cavity and a morphometric comparison of the nasal turbinates with other visualization techniques.

A non-invasive imaging modality, computed tomography (CT), was used to visualize changes in nasal turbinates of anesthetized pigs over a 12-week observation period (pigs were 14 wk of age at study week 0). Normal, non-infected pigs were compared to pigs with mild challenge-induced atrophic rhinitis (AR) in order to detect subtle differences in morphology. To determine feasibility for time course studies in future experiments, morphometric quantitation at the level of the 2nd premolar (turbinate area ratio or TAR) in cross-section CT images at multiple timepoints was done. Additionally, at study termination, the TAR determined from CT images, magnetic resonance imaging (MRI), and wet tissue (WT), were compared to each other and to the standard subjective measure, visual scoring. There were no statistically significant differences between the control and AR groups at CT imaging dates of 0, 3, 6, 9, or 12 wk (P = 0.182). However, a statistically significant decrease in TAR measurements over time (P = 0.015) was observed in both groups, with lower mean values observed on Weeks 3 and 6 before rebounding to baseline values at study termination. At Week 12 (termination of the study), the TAR measurements derived from CT, MRI, and WT were not statistically different from one another (P = 0.220) and the treatment group-by-method interaction was not significant (P = 0.800). This provided evidence of equivalency of the techniques. Mean values for normal and infected groups were not significantly different based on either TAR imaging methods (P = 0.552) or visual scores (P = 0.088). Thus, the current study demonstrated that CT was an acceptable alternative imaging modality which could be used for quantitation of turbinate changes in snouts of live pigs to provide data comparable to tissue taken at necropsy. Computed tomographic imaging would allow non-invasive tracking of disease or treatment responses within individual animals over time. Morphometric analysis of the TAR was equivalent between the CT, MRI, and WT specimens.

Animals↗
PubMed1997

Functional differences in the interaction of arrestin and its splice variant, p44, with rhodopsin.

Arrestin quenches signal transduction in rod photoreceptors by blocking the catalytic activity of photoactivated phosphorylated rhodopsin toward the G protein, transducin (Gt). Rod cells also express a splice variant of arrestin, termed p44, in which the last 35 amino acids are replaced by a single Ala. In contrast to arrestin, this protein has been reported to bind to both the phosphorylated and nonphosphorylated forms of the activated receptor. In this study, we analyzed formation of the rhodopsin-p44 complex in vitro. Like arrestin, p44 stabilized the meta II (MII) photoproduct relative to forms MI and MIII and did not interact measurably with the apoprotein opsin. However, several differences between p44 and its parent protein were found: (i) p44 binds to nonphosphorylated MII with a much lower affinity (KD = 0.24 microM) than to phosphorylated MII (P-MII) (KD = 12 nM); arrestin binds only to P-MII (KD = 20 nM); (ii) p44 interacted also with truncated MII (329G-Rho MII), which lacked the sites of phosphorylation; (iii) with both MII and P-MII, the activation energy of complex formation with p44 was lower than that found for arrestin (70 kJ/mol instead of 140 kJ/mol); and (iv) InsP6 inhibited poorly the interaction between p44 and P-MII, but it strongly inhibited the interaction between arrestin and P-MII. Extrapolation of the measured on-rates to physiological conditions yielded reaction times for the binding of p44 to activated rhodopsin. The data suggest that the splice variant, p44, and its parent protein, arrestin, play different roles in phototransduction. The physiological significance of these differences remains to be determined.

Animals↗
PubMed1997

Functional expression of bovine opsin in the methylotrophic yeast Pichia pastoris.

The methylotrophic yeast Pichia pastoris was examined for functional expression of bovine opsin. An expression plasmid was constructed where the bovine opsin gene was placed downstream from the P. pastoris alcohol oxidase 1 gene promoter and fused at its amino-terminus to the acid phosphatase secretion signal. Quantitative-competitive PCR analysis of a stable yeast transformant showed that one copy of the opsin gene was integrated into the yeast genome. The expression level in this transformant corresponded to approximately 0.3 mg of opsin per liter of cell culture (A600 = 1.0). Sucrose density sedimentation analysis indicated that the opsin was associated exclusively with the membrane fraction. Similar to retinal opsin, P. pastoris-expressed opsin migrated as a single band of approximately 37 kDa on SDS-PAGE and showed high mannose N-glycosylation. A portion of the expressed opsin (approximately 4-15%) reacted with 11-cis-retinal to form the rhodopsin chromophore (lambda max 500 nm), and after purification showed ground and excited state spectral characteristics indistinguishable from those of the native pigment. Further, the metarhodopsin-II-mediated G-protein-activating potential of yeast expressed rhodopsin was similar to that of native rhodopsin. These results show that P. pastoris cells have the capacity to functionally express bovine opsin.

Alcohol Oxidoreductases↗
PubMed1997

Short wavelength-sensitive opsins from the Saharan silver and carpenter ants.

We have previously cloned the opsins coding for the long-wavelength visual pigments from the Saharan silver ant and carpenter ant. Here we report two new cDNA clones isolated from cDNA libraries which also code for opsin proteins. These cDNAs code for deduced proteins with 369 amino acids which are 91% identical to each other, but only 38% identical to the previously cloned opsins. Phyletic comparisons suggest that these opsins are likely the ultraviolet sensitive visual pigments, a conclusion that is supported by the presence of a phenylalanine at the counterion position in the third transmembrane segment.

Animals↗
PubMed1997

The Chronic Pain Grade questionnaire: validation and reliability in postal research.

The Chronic Pain Grade questionnaire has been proposed as an interview-administered, multi-dimensional measure of chronic pain severity in selected populations with chronic pain in the United States of America. It has not previously been tested in the United Kingdom, in self-completion form or in an unselected general population. We undertook a postal survey to assess its reliability, validity and acceptability in these circumstances, using a general practice population in Scotland, with a practice population of 11202 patients. A random sample of 400 patients aged over 18 was drawn, stratified for age, gender and receipt or non-receipt of regular prescriptions for pain-relieving medication. The dimensions and sub-scales of the Chronic Pain Grade were compared with the SF-36 general health questionnaire and questions relating to duration of any pain and attempts to seek treatment for this. The methodological approach proposed by Streiner and Norman (1989) was used to assess validity and reliability. A response rate of 76% was achieved. Cronbach's alpha was > 0.9 and item-total correlations were all high, indicating good internal consistency and reliability. Validity was confirmed by psychometric testing, including confirmatory factor analysis. Good correlations with comparable dimensions of the SF-36 general health questionnaire confirmed convergent validity. Construct validity was confirmed by testing scores against duration of pain and treatment sought for pain. We concluded that the Chronic Pain Grade questionnaire is a useful, reliable and valid measure of severity of chronic pain. It translates well into UK English and is acceptable in general population postal research.

Chronic Disease↗