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Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1998

A common human beta globin splicing mutation modeled in mice.

The betaIVS-2-654 C-->T mutation accounts for approximately 20% of beta thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to beta0 thalassemia. To provide an animal model for testing therapies for correcting splicing defects, we have used the "plug and socket" method of gene targeting in murine embryonic stem cells to replace the two (cis) murine adult beta globin genes with a single copy of the human betaIVS-2-654 gene. No homozygous mice survive postnatally. Heterozygous mice carrying this mutant gene produce reduced amounts of the mouse beta globin chains and no human beta globin, and have a moderate form of beta thalassemia. The heterozygotes show the same aberrant splicing as their human counterparts and provide an animal model for testing therapies to correct splicing defects at either the RNA or DNA level.

Animals↗
PubMed1998

Analysis of complement receptor type 1 (CR1) expression on erythrocytes and of CR1 allelic markers in Caucasian and African American populations.

CR1 expression on erythrocytes (E) is regulated by an element that is tightly linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H allele) or low (L allele) amounts, respectively. When age-fractionated E of donors heterozygous for both the H and L alleles and for CR1 allotypes of differing molecular weights were analyzed in Western blots, the product of the L allele appeared to have an increased rate of loss during cell aging. A coding sequence polymorphism of CR1 predicted to cause a Pro-->Arg substitution in its proximal extramembranous region was tightly linked in Caucasians to the site of the HindIII RFLP. However, neither this polymorphism nor the HindIII RFLP correlated with CR1 expression among African Americans. Relative instability of CR1 encoded by the L allele thus may derive from another coding sequence polymorphism, or may require both the Pro-->Arg substitution and epistatic effects of another polymorphic gene.

Alleles↗
PubMed1998

Notch signalling and the control of cell fate choices in vertebrates.

Signals delivered via Notch and its ligands Delta and Serrate control developmental choices made by individual cells according to the states of their immediate neighbours. Lateral inhibition mediated by Notch governs neurogenesis. In the inner ear, it generates fine-grained patterns of contrasting cell types. In stem-cell systems, it may regulate the decision to differentiate. Notch signalling can create specialised cells at gene expression boundaries, as at the limb-bud apex. It is crucial for segmentation of the mesoderm into somites, for development of skin appendages, and for many other functions that we do not yet understand.

Animals↗
PubMed1998

What is primary care? Developments in Britain since the 1960s.

Since 1994, health policy in the UK has focused explicitly on making the NHS 'primary care-led'. However, the meaning of primary is contested by different health professions and by policy-makers. This paper charts the major points of debate since the 1960s and suggests that there are limitations as to what general practice can be expected to deliver in respect of primary care.

Community Health Services↗
PubMed1998

Peter B. Samuels Award. Restenosis after percutaneous transluminal angioplasty.

BACKGROUND: Determine the feasibility of studying the natural history of the atherosclerotic plaque following percutaneous transluminal angioplasty (PTA), using duplex scanning. METHODS: Twenty-three patients with 40 stenoses (>70% and <5 cm in length) in the iliac and femoro-popliteal segments were studied by duplex scanning before PTA, on day 1, weekly for 8 weeks, and at 3 months, 6 months, and 1 year. The following measurements were made: thickness of the plaque, minimal lumen diameter (MLD), and peak systolic velocity ratio (PSVR). A PSVR >2.0 was used to indicate >50% lumen diameter reduction. RESULTS: Thirty stenoses were available for measurement and analysis. Mean reduction in plaque thickness after angioplasty was greater in echolucent plaques (2.33 +/- 0.9 mm) than echogenic plaques (0.83 +/- 0.6 mm; P < 0.0001). Successful angioplasty (PSVR <2.0) and increase in MLD in echolucent plaques was the result of plaque compression; in echogenic plaques, of wall dilatation. The incidence of restenosis (PSVR >2.0) at 6 months was 12 of 30 (40%) remaining unchanged at 1 year; of the lesions that restenosed, 33% recurred before week 8 and the remainder between weeks 8 and 24, suggesting different mechanisms. During follow-up, all plaques showed "growth"; <2 mm in 17 (57%; group A) and >2 mm in the remaining 13 (43%; group B). The incidence of restenosis (PSVR >2.0) was 4 of 17 (23%) in group A and 8 of 13 (61%) in group B (P <0.05). CONCLUSION: Duplex scanning provides valuable information on both luminal diameter and plaque thickness; it may be used to study the natural history of plaques following angioplasty and also the effects of therapeutic agents aimed at reducing restenosis.

Angioplasty, Balloon↗
PubMed1998

Viridans streptococcal bacteremia after esophageal stricture dilation.

BACKGROUND: The incidence of bacteremia with organisms that may cause infective endocarditis after esophageal stricture dilation is unknown. There is disagreement among physicians regarding the need for antibiotic prophylaxis for patients with valvular heart disease undergoing dilation. Our aim was to determine the frequency and duration of bacteremia associated with esophageal stricture dilation. METHODS: Blood cultures were obtained before and after stricture dilation in patients without valvular heart disease and in a control group of patients undergoing upper endoscopy without dilation. RESULTS: A total of 103 patients undergoing dilation and 50 control patients were studied; 22 of 103 patients (21%) undergoing dilation had at least one post-procedure blood culture positive for viridans streptococcus, compared with 1 of 50 (2%) of control patients (p = 0. 001). Blood cultures obtained 1 minute after stricture dilation were positive for viridans streptococcus in 19 of 81 (23%), in 16 of 96 (17%) 5 minutes post-dilation, and in 3 of 63 (5%) 20 to 30 minutes post-dilation. Of the 19 patients with viridans streptococcus bacteremia 1 minute after dilation, cultures were still positive in 14 of 19 (74%) at 5 minutes and in 2 of 19 (10%) 20 to 30 minutes post-dilation. CONCLUSIONS: These data support the use of antibiotic prophylaxis before esophageal stricture dilation for patients with valvular heart disease at risk for the development of infective endocarditis.

Antibiotic Prophylaxis↗
PubMed1998

Use of USPIO-induced magnetic susceptibility artifacts to identify sentinel lymph nodes and lymphatic drainage patterns. I. Dependence of artifact size with subcutaneous Combidex dose in rats.

Subcutaneously administered Combidex contrast agent produced characteristic magnetic susceptibility artifacts in gradient-echo (GE) images of rat brachial and axillary lymph nodes. These artifacts were useful in the rapid location and identification of normal sentinel lymph nodes. A linear dose response was observed with maximum artifact size in transverse images and was used noninvasively to study lymphatic drainage patterns.

Animals↗
PubMed1998

Echocardiographic quantitation of mitral regurgitation: a new Doppler technique.

Our objective is to develop a new transthoracic Doppler echocardiographic technique to determine mitral regurgitant fraction. The standard color Doppler method for assessment of mitral regurgitation is semiquantitative and dependent on instrument gain. By using the mitral and aortic valve continuous wave Doppler velocities, one can determine regurgitant fraction. This technique takes into account the flow dependence of the mitral valve area. Two constants, A and B, which represent the flow dependence of the mitral valve area and the ratio of the mitral valve area to aortic valve area at zero flow, respectively, were determined by regression in 36 patients without valvular disease (r = .89). Thirty patients with isolated mitral regurgitation were then studied. The mitral regurgitant fraction was calculated from the following: Regurgitant fraction = 1 - TVIav/Bf[Vmv/(1 - AVmv)]dt, where TVIav is the time velocity integral across the aortic valve, Vmv is the continuous wave velocity across the mitral valve, and A and B are constants. The regurgitant fraction was then compared with color Doppler assessment of mitral regurgitation assessed by independent observers. In patients with mitral regurgitation, there was a strong correlation between standard visual assessment and our new Doppler method (Kendall's tau b rank correlation = 0.65; p < .001). The new Doppler method was able to correctly categorize 90% of patients with mild mitral regurgitation and 88% of patients with severe mitral regurgitation; however, there was poorer agreement with the color Doppler assessment of moderate mitral regurgitation. Mitral regurgitant fraction can be calculated with our new Doppler method. This method is quantitative, objective, nongain dependent, and separates mild from severe mitral regurgitation well.

Aortic Valve↗
PubMed1998

Expression patterns of Notch1, Serrate1, Serrate2 and Delta1 in tissues of the developing chick limb.

Signalling via the receptor Notch, delivered by the ligands Delta and Serrate, plays a key role in many cell fate decisions in both Drosophila and vertebrate development (for review seeArtavanis-Tsakonas, S., Matsuno, K. and Fortini, M.E., 1995. Notch signalling. Science 268, 225-232; Lewis, J., 1996. Neurogenic genes and vertebrate neurogenesis. Curr. Opin. Neurobiol. 6, 3-10; Blair, S.S., 1997. Limb development: marginal fringe benefits. Curr Biol. 7, 686-690; Irvine, K.D. and Vogt, T.F., 1997. Dorsal-ventral signaling in limb development. Curr. Opin. Cell Biol. 9, 867-876). Recently vertebrate homologues of Notch (Notch1; Myat, A., Henrique, D., Ish-Horowicz, D. and Lewis, J., 1996. A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogeneis. Dev. Biol. 174, 233-247) and Serrate (Serrate1 and 2; Myat, A., Henrique, D., Ish-Horowicz, D. and Lewis, J., 1996. A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogeneis. Dev. Biol. 174, 233-247; Hayashi, H., Mochii, M., Kodama, R., Hamada, Y., Mizuno, N., Eguchi, G. and Tachi, C., 1996. Isolation of a novel chick homolog of Serrate and its coexpression with Notch-1 in chick development. Int. J. Dev. Biol. 40, 1089-96; Laufer, E., Dahn, R., Orozco, O.E., Yeo, C.Y., Pisenti, J., Henrique, D., Abbott, U., Fallon, J.F. and Tabin, C., 1996. Expression of Radical fringe in limb-bud ectoderm regulates apical ectodermal ridge formation. Nature 386, 366-373; Rodriguez-Esteban, C., Schwabe, J.W., De La Pena, J., Foys, B., Eshelman, B. and Izpisua-Belmonte, J.C., 1997. Radical fringe positions the apical ectodermal ridge at the dorsoventral boundary of the vertebrate limb. Nature 386, 360-366) were shown to be expressed in early chick limb mesenchyme and apical ridge. However, later expression patterns of these genes and of Delta 1 (Henrique, D. , Adam, J., Myat, A., Chitnis, A., Lewis, J. and Ish-Horowicz, D., 1995. Expression of a Delta homologue in prospective neurons in the chick. Nature 375, 787-790) in vertebrate limbs have not been documented. We have used whole mount in-situ hybridization to document expression patterns of Notch1, Serrate1, Serrate2 and Delta1 within the mesenchyme of the developing chick limb up to stage 31 of development. We show these genes are expressed, in different combinations, in the vasculature, the musculature and the tissues of the handplate.

Animals↗
PubMed1998

Editorial

In this issue of the Journal of Helminthology I have much pleasure in including a selection of papers drawn from two workshops, one on 'Nematode Population Genetics' and another on the 'Ecology of Fish Parasites' held in April 1998 at Exeter during the Spring Meeting of the British Society for Parasitology (BSP).The aim of the workshop on 'Nematode Population Genetics' convened by Dr Mark Viney, University of Edinburgh, is to review the current state of knowledge of this topic and to consider future research priorities. Following Mark Viney's overview, Michael Blouin, Oregon State University, Corvallis, USA, considers the effects of parasite life histories on mitochondrial DNA diversity in nematodes. Marleen Roos et al., Institute for Animal Science and Health and the University of Utrecht, The Netherlands, then review polymorphic DNA markers in the genome of parasitic nematodes whereas in the fourth and final paper of this series Alison Galvani and Sunetra Gupta, University of Oxford, consider the effects of mating probability on the population genetics of nematodes.Two papers from the workshop on the 'Ecology of Fish Parasites', convened by Professor Clive Kennedy, University of Exeter, focus on the community ecology of helminths in fish and include a study by Clive Kennedy et al., University of Exeter and University of Rome on the 'Composition and diversity of helminth communities in eels in the River Tiber: long term changes and comparison with insular Europe'. This is followed by an invited paper by William Font, Southeastern Louisiana University, USA on 'Parasites in paradise: patterns of helminth distribution in Hawaiian stream fishes'.I wish to express my grateful thanks to Mark Viney and Clive Kennedy for their assistance in the publication of these papers for this special issue.

Journal Article↗
PubMed1998

Rapid genotyping of mice with hemoglobinopathies and globin transgenes.

The hematology of the laboratory mouse has been well characterized. Normal genetic differences at the alpha- and beta-globin gene loci serve as useful markers for a wide variety of types of experimental studies. There are a number of naturally occurring or induced mutations that disrupt globin expression and produce thalassemic phenotypes. In addition, much has been learned of the workings of the globin locus control region from studies of transgenic mice, including those with mutations induced by targeted site-specific modifications. After a new mutation or transgene has been created, it must be maintained in living mice, and the genotypes of the offspring must be ascertained. While it is possible to determine genotypes by DNA analyses, such assays are time consuming and relatively expensive. An osmotic challenge test--originally developed for the genotyping of large-deletion alpha-thalassemia mutations in mice--has proven useful in detecting both severe and milder alpha- and beta-thalassemias, as well as some transgenic genotypes in mice carrying human globin genes. Reliable genotyping can, in some cases, be completed within a few minutes with minimal expense. Quantification of red cell fragility for a variety of thalassemic and transgenic mice is described here, along with a simplified test suitable for rapid, routine genotyping. The osmotic challenge test is perfectly reliable for distinguishing genotypes that cause significantly decreased release of hemoglobin from the red cells, but it is also useful for some of the conditions in which overall erythrocyte osmotic fragility is essentially normal.

Animals↗
PubMed1998

Culturally sensitive AIDS educational videos for African American audiences: effects of source, message, receiver, and context.

The importance of using culturally sensitive educational materials in HIV-related interventions with racial and ethnic minority groups is widely recognized. However, little empirical research has been conducted to assess the relative effectiveness of different techniques for creating culturally sensitive AIDS educational videos. Two field experiments with three samples of African American adults (N = 174, 173, and 143) were conducted to assess how source characteristics (race of communicator), message characteristics (multicultural message vs. culturally specific message), and audience characteristics (racial distrust and AIDS-related distrust) influence proximate (perceptions of the message's credibility and attractiveness) and distal (AIDS-related attitudes, beliefs, and behavioral intentions) output variables for AIDS educational videos. In Study 1, an AIDS video with a culturally specific message was rated as more credible, more attractive, and of higher quality than was a video with a multicultural message. The multicultural message was rated less favorably when delivered by a White announcer than when the announcer was Black. In Study 2, the same pattern was replicated with a second community sample and a campus-based sample. Study 2 also indicated that a multicultural message might be more effective if delivered in a culturally specific context, namely, after audience members watch a culturally specific video. Minimal changes were observed in distal outcome variables. It is argued that influencing proximate output variables is necessary, though not sufficient, for effecting long-term change in AIDS-related attitudes, beliefs, and behaviors.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Subacute angle-closure glaucoma as a cause of headache in the presence of a white eye.

Three patients, initially diagnosed with headache syndromes, were subsequently found to have subacute angle-closure glaucoma. In each case, the eye appeared grossly normal and there were no visual symptoms. A comprehensive ophthalmologic examination, including gonioscopy, confirmed the diagnosis. Laser iridotomy was curative with complete resolution of head and face pain. Subacute angle-closure glaucoma is an exception to the maxim that a white eye is not the cause of a painful eye.

Aged↗
PubMed1998

Responding to health changes: a case study of dental health conditions and systems in Japan and Australia.

This paper presents an analysis of the main policy and organisational issues confronting dental health systems in Japan and Australia. Using the changes in the epidemiology of dental disease (the oral disease which still affects much of public dental health planning) as evidence of fundamental differences in the dental health systems of the two countries, the analysis seeks to illuminate, first, the structures and processes in both nations to review and implement changes to educational practices and workforce planning and, second, the constraints on each nation's capability to respond quickly and appropriately to the changing dental health needs. It is argued that Japan's ability to rapidly change its oral health outcomes, its dental educational system and its traditional workforce structure and service-mix, is more constrained than appears to be the case in the Australian dental system. The major barriers to Japan's ability to change appear to lie in both its traditional cultural decision-making processes and in a series of specific health and educational structures which place high reliance on a private educational system for health providers, a national insurance system which rewards treatment under a fee-for-service reimbursement scheme and the lack of a formal, transparent, infra-structure for planning health priorities. Barriers to Australia achieving culturally appropriate oral health outcomes for the next century appear more related to whether national unity in goal setting and implementation strategies can be achieved. The constraints in Australia are related to its federal system and to the low priority given to financing public dental services.

Adolescent↗
PubMed1998

Development of a neutralizing antibody response during acute primary human immunodeficiency virus type 1 infection and the emergence of antigenic variants.

We monitored the primary humoral response to human immunodeficiency virus type 1 infection and showed that, in addition to antibodies to p24 and gp41, antigens which form the basis of most diagnostic assays, the response included a significant antibody response directed to the gp120 region of the infecting viral quasispecies. When tested in a recombinant virus neutralization assay, these antibodies were capable of inhibiting viral growth. We found the primary viral quasispecies to solely utilize the CCR-5 chemokine receptor; however, recombinant viruses differed in their cytopathology and in their sensitivity to beta-chemokine inhibition of viral growth. Sequence analysis of the gp120 open reading frames showed that amino acid changes in the C1 (D-->G at position 62) and C4 (V-->A at position 430) regions accounted for the phenotypic differences. These data demonstrate that early in infection, polymorphism exists in envelope glycoprotein coreceptor interactions and imply that therapeutic strategies targeted at this step in the viral life cycle may lead to rapid resistance.

Amino Acid Sequence↗
PubMed1998

Public health interventions to encourage TB class A/B1/B2 immigrants to present for TB screening.

From 1985 to 1995 the proportion of all Santa Clara County, California (SCC), tuberculosis (TB) cases among recent immigrants climbed 73% (137 to 237). In SCC the efficient and cost-effective means encouraging TB Class A/B1/B2 immigrants (TBIMs) to present for TB screening and the prevalence of active TB among them were never investigated. We studied all TBIMs entering SCC from October 1, 1995 to June 30, 1996, notified to SCC by the CDC's Division of Quarantine (DQ). Encouraging TBIMs to seek TB screening, we sent letters to them promptly on the DQ notification, followed sequentially by phone calls and home visits. We determined the outcome of screening and its cost. We screened 314 of 323 (97.2%) TBIMs including 79 of 323 TBIMs who presented prior to interventions, 213 of 314 (87.3%) who responded to letters, 17 (7%) to phone calls, and 5 (2%) to home visits. Of 283 TBIMs screened 16 (5.7%) had active TB. To locate one TBIM cost $9.90 by letter, $43.25 by phone, and $129.88 by home visit. Locating one TB case cost $175.88 by letter, $696.26 by phone call. The prevalence of active TB in TBIMs is high. Our interventions resulted in low-cost TB screening and high-yield identification of active TB cases. We recommended that health departments develop a system for encouraging TBIMs to present for prompt TB screening.

California↗
PubMed1998

Delta-Notch signalling and the patterning of sensory cell differentiation in the zebrafish ear: evidence from the mind bomb mutant.

Mechanosensory hair cells in the sensory patches of the vertebrate ear are interspersed among supporting cells, forming a fine-grained pattern of alternating cell types. Analogies with Drosophila mechanosensory bristle development suggest that this pattern could be generated through lateral inhibition mediated by Notch signalling. In the zebrafish ear rudiment, homologues of Notch are widely expressed, while the Delta homologues deltaA, deltaB and deltaD, coding for Notch ligands, are expressed in small numbers of cells in regions where hair cells are soon to differentiate. This suggests that the delta-expressing cells are nascent hair cells, in agreement with findings for Delta1 in the chick. According to the lateral inhibition hypothesis, the nascent hair cells, by expressing Delta protein, would inhibit their neighbours from becoming hair cells, forcing them to be supporting cells instead. The zebrafish mind bomb mutant has abnormalities in the central nervous system, somites, and elsewhere, diagnostic of a failure of Delta-Notch signalling: in the CNS, it shows a neurogenic phenotype accompanied by misregulated delta gene expression. Similar misregulation of delta ; genes is seen in the ear, along with misregulation of a Serrate homologue, serrateB, coding for an alternative Notch ligand. Most dramatically, the sensory patches in the mind bomb ear consist solely of hair cells, which are produced in great excess and prematurely; at 36 hours post fertilization, there are more than ten times as many as normal, while supporting cells are absent. A twofold increase is seen in the number of otic neurons also. The findings are strong evidence that lateral inhibition mediated by Delta-Notch signalling controls the pattern of sensory cell differentiation in the ear.

Animals↗