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Biomedical subjects

D J Lewis

Publications and source records attributed to D J Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1997

Characterization of B-cell responses to Chlamydia trachomatis antigens in humans with trachoma.

The circulating B-cell responses to Chlamydia trachomatis of 60 children and 34 adults in The Gambia were characterized in a cross-sectional study of different grades of trachoma, using the enzyme-linked immunospot (ELISPOT) assay. Antibody-secreting cells (ASCs) specific to chlamydial major outer membrane protein (MOMP), heat shock protein 60, and whole elementary bodies were detected in children with no evidence of ocular disease, and the immunoglobulin (IgA) response was significantly increased in those with follicular trachoma. In marked contrast, children with the most intense ocular inflammation paradoxically had an almost completely absent B-cell response of all isotypes and to all chlamydial antigens, but with normal serum IgG and IgA responses, which was even lower than in the group with no ocular inflammation. Adults with or without evidence of trachomatous scarring had equivalent numbers of circulating B cells, principally IgA, to all chlamydial antigens. Plasmablasts secreting antibodies to MOMP were present in the urine of children in the absence of urogenital infection detectable by PCR, and relative numbers were 8 to 25 times higher than in blood, suggesting site-specific homing within a common mucosal immune system. These results suggest that ELISPOT assay of ongoing B-cell responses detects suppression of chlamydia-specific IgA ASCs during the proinflammatory response to ocular chlamydial infection seen in intense trachoma, which may play a role in tissue damage leading to trachomatous scarring.

Adult↗
PubMed1996

Extraction of maleic hydrazide residues from potato crisps and their determination using high-performance liquid chromatography with UV and atmospheric pressure chemical ionisation mass spectrometric detection.

A method was required for the determination of maleic hydrazide residues in potato crisps. A published method for the extraction of the analyte from onions and potatoes was evaluated and found to be inappropriate due to the inability of the extracting solvent to penetrate the oily matrix. A method was developed to overcome this problem; the resulting recovery data (mean = 92.9%, R.S.D. = 8.3%, n = 16) confirmed its efficiency, and was used to analyse 48 retail potato crisp samples. To confirm possible residues identified by screening with HPLC-UV, an HPLC-atmospheric pressure chemical ionization MS method was developed. There was good agreement between the data obtained from the two detection techniques (R2 = 0.978, slope = 1.11).

Chromatography, High Pressure Liquid↗
PubMed1996

Children's analysis of derivational suffix meanings.

This note examined the relation between school-age children's production and comprehension of derivational suffixes in nonsense words and their knowledge of suffix meaning in real derivatives. Results indicated that knowledge of derivational suffixes was used often in defining low-frequency derivatives and that it was significantly correlated with suffix production in the nonsense task. In addition, suffix productivity was found to be an important factor determining the comprehension as well as the production of particular suffixes to convey a range of meanings.

Adolescent↗
PubMed1996

Cost effectiveness of cataract surgery. A comparison of conventional extracapsular surgery and phacoemulsification at Flinders Medical Centre.

PURPOSE: To compare the cost of conventional extracapsular cataract surgery and phacoemulsification at Flinders Medical Centre. METHODS: The costs of the two forms of cataract surgery were assessed over a 12-month period. During this period 410 cataract operations were performed. SETTING: The cataract surgery was carried out in a dedicated day surgery unit in a teaching hospital. OUTCOME MEASURE: The direct, indirect and tangible costs were measured. RESULTS: Conventional extracapsular cataract surgery with posterior chamber lens implant costs $1000.85 and phacoemulsification with lens implantation costs $1231.00. CONCLUSIONS: Although conventional extracapsular surgery generates slightly lower costs than phacoemulsification, the cost difference is small. In generating these figures, some assumptions must be made and the real difference may prove to be less than this.

Cataract Extraction↗
PubMed1995

A method to screen T lymphocyte epitopes after oral immunisation of humans: application to cholera toxin B subunit.

The response to oral immunisation of humans with classical biotype cholera toxin B subunit was studied to identify immunodominant T lymphocyte determinants. The in vitro proliferative response to pools of 12-mer peptides and larger peptides used individually was analysed by a novel statistical approach, and identified an immunodominant region in residues 70-79 in immunised subjects, when either pools or individual peptides were employed. In contrast, a patient infected with El Tor biotype had a dominant response to residues 40-60. The statistical software employed in this study may enable efficient screening of antigens for immunodominant T lymphocyte determinants when blood precursor frequencies are low following immunisation, and may therefore be of special relevance to mucosal vaccines.

Administration, Oral↗
PubMed1995

Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141b).

A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.

Administration, Inhalation↗
PubMed1995

Segmentation of mammograms using multiple linked self-organizing neural networks.

A possible first stage in the analysis of the mammographic scene is its segmentation into four major components: background (the nonbreast area), pectoral muscle, fibroglandular region (parenchyma), and adipose region. An algorithm has been developed for this task. It is based on the classification of a feature vector constructed from statistical measures of texture calculated at two window sizes. Separate self-organizing neural networks are trained on sample data taken from each of the four regions. The feature vectors from the entire mammogram are then classified with the trained networks linked via a decision logic. To overcome the variability of texture between mammograms the algorithm uses data from a mammogram to classify itself in a staged approach consisting of several binary decisions. The training regions for each successive stage are determined from geometric information produced by the previous stages. The dataset in the study consisted of thirty (fifteen pairs) digitized normal mammograms of variable radiographic appearance. As a measure of performance, the outlines of the parenchyma were compared to those drawn by a radiologist experienced in reading mammograms. Comparison of the areas and perimeters generated by the human and computer observers gives a relationship with correlation coefficients of 0.74 and 0.59 for each measure, respectively. The overlapping areas of the parenchymas segmented by the observers normalized by the combined area was also calculated for each case. The mean and standard deviation of this measure was 0.69 +/- 0.12.

Adipose Tissue↗
PubMed1994

Characterization of the circulating T-cell response after oral immunization of human volunteers with cholera toxin B subunit.

The kinetics and phenotypic characterization of the in vitro cell proliferative response to the B subunit of cholera toxin were studied using peripheral blood mononuclear cells taken from human volunteers at frequent time points after primary and booster oral immunizations. The cells induced to proliferate by oral immunization secreted IL-3, and lipopolysaccharide depletion and depletion of B cells did not affect proliferation. Flow cytometry demonstrated that activated cells were CD3- and CD4-positive. These findings indicate primed T cells proliferating specifically to the B subunit. The kinetics of the response suggested trafficking in the peripheral circulation of primed T cells from the gut, with a peak stimulation index of between 7 and 93 after first immunization, and a precursor frequency of primed cells of between 1 in 25,400 and 1 in 72,390. There was close correlation between the serum antitoxin IgA antibody levels and observed proliferation.

Administration, Oral↗
PubMed1994

Immunohistochemical expression of P53 tumor suppressor gene protein in adult germ cell testis tumors: clinical correlation in stage I disease.

P53 tumor suppressor gene protein immunostaining was evaluated in the primary tumor of adult testicular germ cell cancer to assess if P53 expression would serve as a clinically useful tumor marker. Representative archival tissues from 152 orchiectomy specimens were studied for P53 immunohistochemistry. Seminoma and nonseminomatous germ cell tumor constituents revealed P53 expression via immunohistochemistry in 90% and 94% of the cases, respectively. For seminoma, there was a trend toward decreased P53 expression with advancing stage. For nonseminomatous germ cell tumor, although all cellular components showed variable P53 expression, P53 expression in embryonal carcinoma constituents increased among stages of disease. A third of pathological stage I cancer patients exhibited 2+ or greater P53-embryonal staining compared with 61% with stage II (p = 0.0670) and 67% with stage III (p = 0.0815) disease, respectively (Kruskal-Wallis, 2-sided test). As a secondary objective, we wanted to determine if P53 immunohistochemistry would be useful to predict occult disease in clinical stage I nonseminomatous germ cell tumor. This group was studied for P53-embryonal immunohistochemistry, the presence of vascular invasion and the quantitative determination of percentage of embryonal carcinoma in the primary tumor in a multivariate fashion to assess if these tests could be clinically useful to predict occult disease. Degree of P53 immunostaining of the embryonal component in the primary tumor was statistically greater for stage II by univariate logistic regression analysis (p = 0.0362). Similarly, the per cent embryonal cancer (p = 0.0002) and vascular invasion (p = 0.0005) were highly significant as predictors of occult stage II disease via the univariate testing. By multivariate logistic regression analysis, the model consisting of per cent embryonal cancer and vascular invasion provided the best prediction of occult disease in the clinical stage I cohort. In addition, this model had the highest sensitivity and specificity of all multivariate models considered. The addition of P53-embryonal staining did not improve predictability nor sensitivity/specificity. The P53 tumor suppressor gene protein is expressed to some degree in most testicular germ cell tumors and degree of staining/expression varies according to stage of disease. From the standpoint of a clinically useful primary tumor risk factor for predicting occult disease, vascular invasion by the tumor and percentage of embryonal carcinoma component in the tumor are more useful than P53 immunohistochemistry.

Adult↗
PubMed1994

Immunohistologic detection of prostate cancer pelvic lymph node micrometastases: correlation to preoperative serum prostate-specific antigen.

OBJECTIVE: To test the hypothesis that prostate cancer lymph node (LN) micrometastases, undetected by standard histology, might be found using sensitive immunohistologic methods and may correlate to preoperative prostate-specific antigen (PSA) levels. METHOD: Archival paraffin blocks of pelvic lymphadenectomy specimens from radical prostatectomy were blindly submitted for immunostaining using pan-cytokeratin monoclonal antibody SB-3, as well as antibodies directed against PSA. Automated immunostaining was performed on a Ventana Medical Systems 320 immunostainer. As a positive control, 7 cases with known nodal metastases by standard histology were blindly analyzed and all has detectable micrometastases by this methodology. RESULTS: For 13 patients with PSA < 10.1 (8%) had LN micrometastases detected. For 10 patients with PSA between 10 and 20 and for 9 patients with PSA > 20, no occult metastases were detected. We did find previously undetected prostate cancer (CaP) LN micrometastases in 1 of 32 (3%) clinically localized prostate cancer patients who had undergone radical prostatectomy. In many LNs, cytokeratin stains cross-reacted and stained individual plasma cells, whereas in the positive metastatic case, a cluster/nest of CaP cells were reactive. To the unfamiliar observer, the pitfall of false-positive results because of nonspecific cytokeratin staining must be considered. These results are in exact agreement with another recent study which also found only a 3 percent incidence of unsuspected pelvic lymph node micrometastases in clinically localized CaP utilizing similar methods. CONCLUSIONS: Our hypothesis was not substantiated: LN micrometastases were uncommon and did not correlate to serum PSA. Unlike studies with breast cancer, occult micrometastatic nodal disease not appreciated by standard methods appears to be uncommon in clinically localized prostatic carcinoma.

Humans↗
PubMed1994

Perirenal liposarcoma containing extramedullary hematopoiesis associated with renal cell carcinoma.

We present the first reported case of a perirenal well-differentiated liposarcoma containing extramedullary hematopoiesis associated with an ipsilateral T2N0M0 renal cell carcinoma. This patient, a seventy-one-year-old white male, had no known hematologic disorder and on preoperative evaluation had similar radiographic findings identified within the contralateral perirenal space. Pathologic evaluation after radical nephrectomy reported the perirenal mass to consist only of myelolipomatous change, however, further review identified liposarcoma.

Aged↗
PubMed1994

Immune response following oral administration of cholera toxin B subunit to HIV-1-infected UK and Kenyan subjects.

OBJECTIVE: To determine the effect of HIV-1 infection on immunoglobulin (Ig) G and IgA antibody response and circulating antibody forming cell response to oral immunization with the B subunit of cholera toxin. DESIGN: Healthy UK volunteers, and HIV-1-positive UK and Kenyan volunteers at different clinical stages of HIV-1 infection received two oral immunizations. CD4+ T cells, serum beta 2-microglobulin and neopterin were measured as surrogate markers of disease stage, and correlated with immunization response. METHODS: Serum antitoxin IgG and IgA measured by enzyme-linked immunosorbent assay and antitoxin IgG, IgA and IgM antibody-forming cells detected by enzyme-linked immunospot assay at different times after two oral immunizations. RESULTS: UK HIV-positive volunteers (mean CD4+ T cell count, 52 x 10(6)/l) responded poorly to primary and booster immunization. HIV-infected Kenyans (752 x 10(6)/l CD4+ T cells) had a significant primary and booster antibody response, whereas those with a mean CD4+ T cell count 186 x 10(6)/l had an insignificant primary, but significant booster response. Two oral immunizations induced antibody responses in HIV-positive Kenyan groups (who may have prior immunity from exposure to environmental bacterial toxins) of similar or greater magnitude to healthy UK volunteers. CONCLUSIONS: Mucosal immunization may recall immune memory and be of benefit in early and moderately advanced clinical HIV disease. The findings have important clinical implications in that mucosally targeted vaccines are potentially useful in this group of patients.

Administration, Oral↗
PubMed1994

Immunoglobulin G antibody responses to polyvalent pneumococcal vaccine in children in the highlands of Papua New Guinea.

The immunoglobulin G (IgG) antibody responses to a pneumococcal polysaccharide vaccine were examined for 480 children aged 3 months to 5 years and living in Tari, Southern Highlands Province, Papua New Guinea. Antipneumococcal IgG to the seven serotypes most frequently causing invasive disease (types 2, 5, 6B, 7F, 14, 19F, and 23F) was measured by an enzyme-linked immunosorbent assay in serum collected before vaccination and 1 and 6 months after vaccination. Prevaccination antibody levels fell rapidly after 3 months of age and remained low throughout the first 2 years of life. One month after vaccination, geometric mean titers of antipneumococcal IgG to serotypes 2, 7F, 23F, and 5 were at least twice those of antibodies in nonvaccinated children of the same age from the ages of 5, 6, 9, and 12 months onwards, respectively; postvaccination antibody responses to serotypes 6B, 14, and 19F rose gradually during the second year of life. Elevated antibody titers to serotypes 2 and 7F were maintained 6 months after vaccination. Thus, young Papua New Guinean children are capable of mounting a good immune response to some pneumococcal capsular polysaccharides from a young age, and the antibody responses to capsular polysaccharides are consistent with studies in developed countries. However, in Papua New Guinea, the serogroup distribution of invasive disease matches the immunogenic components of the pneumococcal polysaccharide vaccine more closely than in developed countries, a fact which helps to explain the results of controlled trials in Papua New Guinea, in which this vaccine prevented death and severe morbidity from pneumonia in young children.

Age Factors↗
PubMed1993

Structure of bis[cis-1,2-bis(diphenylphosphino)ethylene] dichlororhenium(II) hexane solvate.

[ReCl2(C26H22P2)2].C6H14 (I), M(r) = 1136.11, monoclinic, P2(1)/c, a = 11.426 (2), b = 13.078 (2), c = 17.323 (3) A, beta = 95.27 (1) degrees, V = 2577.7 (6) A3, Z = 2, Dx = 1.46 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 26.5 cm-1, F(000) = 1150, T = 296 K, R = 0.034 for 3269 [Fo2 > 3 sigma(Fo2)] reflections. The Re atom in (I) is located on an inversion point, fixed at the origin. One Cl and a complete tertiary phosphine ligand (Ph2PCHCHPPh2) are situated around the Re atom so as to generate a pseudo-octahedral geometry with a P1--Re--P2 angle of 79.07 (5) degrees and P1--Re--P2' angle of 100.93 (5) degrees. The Re--Cl, Re--P1 and Re--P2 distances are 2.432 (2), 2.401 (2) and 2.398 (2) A, respectively. Bond distances and angles for the phenyl rings range from 1.34 (1) to 1.41 (1) A and 117.4 (6) to 122.0 (7) degrees with averages of 1.38 (1) A and 120.0 (1) degrees, respectively.

Crystallography, X-Ray↗
PubMed1993

Circulating cellular immune response to oral immunization of humans with cholera toxin B-subunit.

Peripheral blood mononuclear cells were taken from subjects before and after oral immunization with cholera toxin B-subunit. Cells obtained from naive volunteers before immunization did not proliferate in vitro to B-subunit. Oral immunization induced a proliferative response in all volunteers with a peak stimulation index of 20, and was detected up to 1 year later. The proliferative response kinetics suggest the appearance in the blood of primed T cells from the gut coinciding with the disappearance of primed plasmablasts from the circulation, supporting the concept of a common mucosal immune system in man for T and B cells.

Administration, Oral↗
PubMed1993

Factors affecting the acquisition of Plagiorchis noblei (Trematoda: Plagiorchiidae) cercariae by black fly (Diptera: Simuliidae) larvae and the effect of metacercariae on host survival.

Larvae of 4 species of black flies, Prosimulium mixtum, Simulium vittatum, S. decorum and Stegopterna mutata, were exposed in the laboratory to cercariae of the digenean Plagiorchis noblei in flowing water. Prevalence and intensity of infection of all species varied directly with exposure intensity and decreased with increasing water velocity; prevalence increased with larval size. Infection levels for P. mixtum were higher than for the 3 other species. Mortality among infected larvae of all species was 3 times that of controls. Exposure of black fly larvae to P. noblei cercariae may adversely affect their survival.

Animals↗