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Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2003

Maternal and congenital syphilis in Bolivia, 1996: prevalence and risk factors.

OBJECTIVES: The present study was carried out in seven maternity hospitals to determine the prevalence of maternal syphilis at the time of delivery and the associated risk factors, to conduct a pilot project of rapid syphilis testing in hospital laboratories, to assure the quality of syphilis testing, and to determine the rate of congenital syphilis in infants born to women with syphilis at the time of delivery--all of which would provide baseline data for a national prevention programme in Bolivia. METHODS: All women delivering either live-born or stillborn infants in the seven participating hospitals in and around La Paz, El Alto, and Cochabamba between June and November 1996 were eligible for enrolment in the study. FINDINGS: A total of 61 out of 1428 mothers (4.3%) of live-born infants and 11 out of 43 mothers (26%) of stillborn infants were found to have syphilis at delivery. Multivariate analysis showed that women with live-born infants who had less than secondary-level education, who did not watch television during the week before delivery (this was used as an indicator of socioeconomic status), who had a previous history of syphilis, or who had more than one partner during the pregnancy were at increased risk of syphilis. While 76% of the study population had received prenatal care, only 17% had syphilis testing carried out during the pregnancy; 91% of serum samples that were reactive to rapid plasma reagin (RPR) tests were also reactive to fluorescent treponemal antibody-absorption (FTA-ABS) testing. There was 96% agreement between the results from local hospital laboratories and national reference laboratories in their testing of RPR reactivity of serum samples. Congenital syphilis infection was confirmed by laboratory tests in 15% of 66 infants born to women with positive RPR and FTA-ABS testing. CONCLUSION: These results indicate that a congenital syphilis prevention programme in Bolivia could substantially reduce adverse infant outcomes due to this disease.

Analysis of Variance↗
PubMed2003

Interleukin 1alpha, interleukin 1beta and interleukin 1 receptor gene polymorphisms in psoriatic arthritis.

OBJECTIVES: To investigate polymorphisms of interleukin (IL) 1alpha, IL-1beta and IL-1 receptor R1 genes in patients with psoriatic arthritis (PsA), their relationship to the age of onset of psoriasis and the pattern of joint involvement. METHODS: One hundred and forty well-characterized patients with PsA were studied. One hundred healthy controls were recruited from primary care. All were genotyped for single-nucleotide polymorphisms in the genes for IL-1alpha (position -889), IL-1beta (position +3953) and IL-1R1 (position +970). The frequencies of the respective variants were compared between patients and controls and in relation to age of onset of psoriasis, to clinical subsets of the disease and to the presence of erosions. RESULTS: All three polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of IL-1alpha -889 CC homozygotes was significantly increased in PsA patients compared with normal controls [58 vs 40%, odds ratio (OR) 2.06, 95%, confidence interval (CI) 1.22-3.47]. The frequency of the IL-1alpha -889 C allele was significantly increased in PsA patients compared with controls (75 vs 65%, OR 1.65, 95% CI 1.11-2.45). In subset analysis there were no other significant differences in allelic frequencies for the IL-1alpha -889 C/T, IL-1beta +3953 C/T and IL-1R1 +970 C/T polymorphisms. CONCLUSIONS: The IL-1 gene complex may play a role in the development of PsA and/or psoriasis or act as a marker for other genes on chromosome 2q12 to 2q13.

Adult↗
PubMed2003

Isolation of cytomegalovirus and foamy virus from the drill monkey (Mandrillus leucophaeus) and prevalence of antibodies to these viruses amongst wild-born and captive-bred individuals.

Drill monkeys (Mandrillus leucophaeus) are an endangered species whose indigenous viral flora is largely unknown. We report here the isolation and characterization of both a cytomegalovirus (DrCMV) and a foamy virus (SFV-drl) from drill monkeys. Phylogenetic analysis of DNA sequence data placed the DrCMV within a primate CMV clade, and showed that SFV-drl was closely related to baboon foamy viruses. ELISA analysis demonstrated that DrCMV shared common epitopes with other primate CMVs but was distinct from human and baboon CMVs. ELISA testing of sera from wild-born and captive-bred drills indicated that the prevalence of antibodies reactive with these two viruses was 93.2% for DrCMV and 20.3% for SFV-drl.

Animals↗
PubMed2003

Does tape facilitate or inhibit the lower fibres of trapezius?

The application of tape to the skin overlying the lower fibres of trapezius is generally thought to facilitate this muscle. However, this facilitation has not been thoroughly investigated. In this study, the effect of tape upon trapezius motoneurone pool excitability was assessed using the trapezius H reflex. The amplitude of the H reflex was measured across four conditions: before tape application, with Endura Fix tape, with the addition of Endura Sports tape and finally with the tape removed. Instead of the expected facilitation of lower trapezius, this tape inhibited lower trapezius activity. On average, the application of Endura Fix tape inhibited trapezius by 4%. The application of Endura Sports tape overlaying the Endura Fix tape inhibited trapezius on average by 22%. This inhibition did not last once the tape was removed. This suggests that any change in shoulder girdle symptoms or movement, which occurs with the application of this particular tape, is not explicable on the basis of the facilitation of the lower fibres of trapezius.

Adult↗
PubMed2003

Endothelial function and coagulant factors in growth hormone-treated hypopituitary adults receiving desmopressin.

Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. L-Deamino-8-D-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 +/- 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 +/- 16 yr). Fifteen healthy controls (group C) (mean age, 48 +/- 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean +/- SD) (A, 3.3 +/- 1.0 g/liter vs. B, 3.5 +/- 0.9 vs. C, 2.6 +/- 0.8, P < 0.05), factor VIII (A, 130% +/- 30% vs. B, 128% +/- 30% vs. C, 104% +/- 35%, P < 0.05) and von Willebrand factor antigen (A, 124% +/- 35% vs. B, 134% +/- 45% vs. C, 93% +/- 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% +/- 2.0% vs. B, 4.7% +/- 1.6%) and was similar to that in the control group (C, 5.7% +/- 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.

Administration, Intranasal↗
PubMed2002

Associated proteins of lens adherens junction.

Cytoplasmic proteins associated with adherens junctions were identified in the chicken ocular lens. The catenins, alpha, beta, and gamma, were present in epithelial and fiber cells, although their pattern of distribution changed with fiber cell differentiation. The sharp decline in alpha-catenin with fiber cell formation and the increasing Triton-insolubility of N-cadherin suggests that another subtype of alpha-catenin exists in the lens.

Adherens Junctions↗
PubMed2002

XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome and prevents CD95- and Bax-induced apoptosis.

Ligation of death receptors or formation of the Apaf-1 apoptosome results in the activation of caspases and execution of apoptosis. We recently demonstrated that X-linked inhibitor-of-apoptosis protein (XIAP) associates with the apoptosome in vitro. By utilizing XIAP mutants, we now report that XIAP binds to the 'native' apoptosome complex via a specific interaction with the small p12 subunit of processed caspase-9. Indeed, we provide the first direct evidence that XIAP can simultaneously bind active caspases-9 and -3 within the same complex and that inhibition of caspase-3 by the Linker-BIR2 domain prevents disruption of BIR3-caspase-9 interactions. Recent studies suggest that inhibition of caspase-3 is dispensable for its anti-apoptotic effects. However, we clearly demonstrate that inhibition of caspase-3 is required to inhibit CD95 (Fas/Apo-1)-mediated apoptosis, whereas inhibition of either caspase-9 or caspase-3 prevents Bax-induced cell death. Finally, we illustrate for the first time that XIAP mutants, which are incapable of binding to caspases-9 and -3 are completely devoid of anti-apoptotic activity. Thus, XIAP's capacity to maintain inhibition of caspase-9 within the Apaf-1 apoptosome is influenced by its ability to simultaneously inhibit active caspase-3, and depending upon the apoptotic stimulus, inhibition of caspase-9 or 3 is essential for XIAP's anti-apoptotic activity.

Apoptosis↗
PubMed2002

Scapular position: the validity of skin surface palpation.

The assessment of the resting position of the scapula forms part of the examination of upper quadrant posture. The purpose of this study was to determine if surface palpation is a valid indicator of actual scapular position. Twelve embalmed shoulders were examined and the actual location of three bony scapular landmarks and three bony thoracic landmarks were compared with surface palpation of these locations. The results, based on the upper value for a distance (with 95% confidence), suggested that the difference between the surface location of the root of the spine of the scapula, the acromial angle and the inferior angle would be less than 0.67 cm, 0.98 cm and 0.46 cm respectively from the centre of the bony locations. The difference between the twelfth thoracic spinous process (SP), the SP corresponding with the root of the spine of the scapula, and the SP corresponding with the inferior angle and the surface points would be 1.46 cm, 1.09 cm and 1.01 cm respectively. The results of this study suggest that surface palpation of scapular location is a valid method for determining the actual location of the scapula. The findings also suggest that surface palpation can determine the location of thoracic landmarks, which may serve as reference points for scapular position.

Aged↗
PubMed2001

IL-18-binding protein protects against lipopolysaccharide- induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice.

IL-18-binding protein (IL-18BP) is a natural IL-18 inhibitor. Human IL-18BP isoform a was produced as fusion construct with human IgG1 Fc and assessed for binding and neutralizing IL-18. IL-18BP-Fc binds human, mouse, and rat IL-18 with high affinity (K(D) 0.3-5 nM) in a BIAcore-based assay. In vitro, IL-18BP-Fc blocks IL-18 (100 ng/ml)-induced IFN-gamma production by KG1 cells (EC(50) = 0.3 microg/ml). In mice challenged with an LD(90) of LPS (15 mg/kg), IL-18BP-Fc (5 mg/kg) administered 10 min before LPS blocks IFN-gamma production and protects against lethality. IL-18BP-Fc administered 10 min before LPS blocks IFN-gamma production induced by LPS (5 mg/kg) with ED(50) of 0.005 mg/kg. Furthermore, IL-18BP-Fc (5 mg/kg) abrogates LPS (5 mg/kg)-induced IFN-gamma production even when administered 6 days before LPS but shows no effect when administered 9 or 12 days before LPS. Given 10 min before LPS challenge to mice primed 12 days in advance with heat-killed Propionibacterium acnes, IL-18BP-Fc prevents LPS-induced liver damage and IFN-gamma and Fas ligand expression. Given at the moment of priming with P. acnes, IL-18BP-Fc decreases P. acnes-induced granuloma formation, macrophage-inflammatory protein-1alpha and macrophage-inflammatory protein-2 production and prevents sensitization to LPS. IL-18BP-Fc also prevents Con A-induced liver damage and IFN-gamma and Fas ligand expression as well as liver damage induced by Pseudomonas aeruginosa exotoxin A or by anti-Fas agonistic Ab. In conclusion, IL-18BP can be engineered and produced in recombinant form to generate an IL-18 inhibitor, IL-18BP-Fc, endowed with remarkable in vitro and in vivo properties of binding and neutralizing IL-18.

Animals↗
PubMed2001

Rapid infusion of intravenous immune globulin in patients with neuromuscular disorders.

The safety and efficiency of a novel method of rapid-infusion IV immunoglobulin (IVIg) were retrospectively reviewed in 50 patients with neuromuscular disorders. There were 89 adverse events after 341 rapid infusions (26%), 3.5% of which were considered to be major (requiring hospitalization) and 66% minor. All patients recovered without sequelae, and there were no deaths. Fourteen of 17 patients (82%) receiving maintenance therapy preferred rapid IVIg infusion because of its convenience. Rapid-infusion IVIg can be given safely and conveniently in many patients with neuromuscular disorders.

Adult↗
PubMed2001

Molecular and phylogenetic analyses of 16 novel simian T cell leukemia virus type 1 from Africa: close relationship of STLV-1 from Allenopithecus nigroviridis to HTLV-1 subtype B strains.

A serological survey searching for antibodies reacting with human T-cell leukemia virus type 1 (HTLV-1) antigens was performed on a series of 263 sera/plasma obtained from 34 monkey species or subspecies, originating from different parts of Africa. Among them, 34 samples exhibited a typical HTLV-1 Western blot pattern. Polymerase chain reaction was performed with three primer sets specific either to HTLV-1/STLV-1 or HTLV-2 and encompassing gag, pol, and tax sequences, on genomic DNA from peripheral blood mononuclear cells of 31 animals. The presence of HTLV-1/simian T-cell leukemia virus type 1 (STLV-1) related viruses was determined in the 21 HTLV-1 seropositive animals tested but not in the 10 HTLV-1 seronegative individuals. Proviral DNA sequences from the complete LTR (750 bp) and a portion of the env gene (522 bp) were determined for 16 new STLV-1 strains; some of them originating from species for which no STLV-1 molecular data were available as Allenopithecus nigroviridis and Cercopithecus nictitans. Comparative and phylogenetic analyses revealed that these 16 new sequences belong to five different molecular groups. The A. nigroviridis STLV-1 strains exhibited a very strong nucleotide similarity with HTLV-1 of the subtype B. Furthermore, four novel STLV-1, found in Cercocebus torquatus, C. m. mona, C. nictitans, and Chlorocebus aethipos, were identical to each other and to a previously described Papio anubis STLV-1 strain (PAN 503) originating from the same primate center in Cameroon. Our data extend the range of the African primates who could be permissive and/or harbor naturally STLV-1 and provide new evidences of cross-transmission of African STLV-1 between different monkey species living in the same environment and also of STLV-1 transmissions from some monkeys to humans in Central Africa.

Africa↗
PubMed2001

Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP.

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant beta-amyloid precursor protein (APP), thus modulating the APP-Abeta (beta-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Abeta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Abeta influences the formation of neurofibrillary tangles. The interaction between Abeta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.

Alzheimer Disease↗
PubMed2001

Identification of a determinant of epidermal growth factor receptor ligand-binding specificity using a truncated, high-affinity form of the ectodomain.

Murine and human epidermal growth factor receptors (EGFRs) bind human EGF (hEGF), mouse EGF (mEGF), and human transforming growth factor alpha (hTGF-alpha) with high affinity despite the significant differences in the amino acid sequences of the ligands and the receptors. In contrast, the chicken EGFR can discriminate between mEGF (and hEGF) and hTGF-alpha and binds the EGFs with approximately 100-fold lower affinity. The regions responsible for this poor binding are known to be Arg(45) in hEGF and the L2 domain in the chicken EGFR. In this study we have produced a truncated form of the hEGFR ectodomain comprising residues 1-501 (sEGFR501), which, unlike the full-length hEGFR ectodomain (residues 1-621, sEGFR621), binds hEGF and hTGF-alpha with high affinity (K(D) = 13-21 and 35-40 nM, respectively). sEGFR501 was a competitive inhibitor of EGF-stimulated mitogenesis, being almost 10-fold more effective than the full-length EGFR ectodomain and three times more potent than the neutralizing anti-EGFR monoclonal antibody Mab528. Analytical ultracentrifugation showed that the primary EGF binding sites on sEGFR501 were saturated at an equimolar ratio of ligand and receptor, leading to the formation of a 2:2 EGF:sEGFR501 dimer complex. We have used sEGFR501 to generate three mutants with single position substitutions at Glu(367), Gly(441), or Glu(472) to Lys, the residue found in the corresponding positions in the chicken EGFR. All three mutants bound hTGF-alpha and were recognized by Mab528. However, mutant Gly(441)Lys showed markedly reduced binding to hEGF, implicating Gly(441), in the L2 domain, as part of the binding site that recognizes Arg(45) of hEGF.

Animals↗
PubMed2001

Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles.

The microtubule-binding protein tau has been implicated in the pathogenesis of Alzheimer's disease and related disorders. However, the mechanisms underlying tau-mediated neurotoxicity remain unclear. We created a genetic model of tau-related neurodegenerative disease by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila melanogaster. Transgenic flies showed key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary tangle formation that is seen in human disease and some rodent tauopathy models. This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.

Acetylcholine↗
PubMed2001

Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP.

We have introduced a targeted mutation in SH2D1A/DSHP/SAP, the gene responsible for the human genetic disorder X-linked lymphoproliferative disease (XLP). SLAM-associated protein (SAP)-deficient mice had normal lymphocyte development, but on challenge with infectious agents, recapitulated features of XLP. Infection of SAP- mice with lymphocyte choriomeningitis virus (LCMV) or Toxoplasma gondii was associated with increased T cell activation and IFN-gamma production, as well as a reduction of Ig-secreting cells. Anti-CD3-stimulated splenocytes from uninfected SAP- mice produced increased IFN-gamma and decreased IL-4, findings supported by decreased serum IgE levels in vivo. The Th1 skewing of these animals suggests that cytokine misregulation may contribute to phenotypes associated with mutation of SH2D1A/SAP.

Amino Acid Sequence↗
PubMed2001

Copper-64-diacetyl-bis(N4-methylthiosemicarbazone): An agent for radiotherapy.

Systemic administration of hypoxia-selective (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) has increased significantly the survival time of hamsters bearing human GW39 colon cancer tumors. Radiotherapy experiments were performed in animals bearing either 7-day-old (0.5-1.0 g) or 15-day-old (1.5-2.0 g) tumors. Studies compared animals treated with a single dose of 0, 4, 6, 7, 8, or 10 mCi of (64)Cu-ATSM (1 Ci = 37 GBq) with or without the vasodilator hydralazine. A multiple dose regimen of 3 x 4 mCi at 72-h intervals was studied also. Single doses of >6 mCi of (64)Cu-ATSM and the dose-fractionation protocol significantly increased the survival time of the hamsters compared with controls. The highest dose, 10 mCi of (64)Cu-ATSM, increased survival to 135 days in 50% of animals bearing 7-day-old tumors, 6-fold longer than control animals' survival (20 days), with only transient leucopenia and thrombocytopenia but no overt toxicity. Human absorbed doses were calculated from hamster biodistribution; the dose-critical organs were the lower large intestine (1.43 +/- 0.19 rad/mCi) and upper large intestine (1.20 +/- 0.38 rad/mCi). High-resolution MRI and positron-emission tomography using a therapeutic administration of 10 mCi were used to monitor tumor volume and morphology and to assess tumor dosimetry accurately, giving a tumor dose of 81 +/- 7.5 rad/mCi. (64)Cu-ATSM has increased the survival time of tumor-bearing animals significantly with no acute toxicity and thus is a promising agent for radiotherapy.

Animals↗
PubMed2001

Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family.

X-linked lymphoproliferative syndrome (XLP; Duncan's disease) is a primary immunodeficiency disease that manifests as an inability to regulate the immune response to Epstein-Barr virus (EBV) infection. Here we examine the ability of the product of the gene defective in XLP, SAP (DSHP/SH2D1A), to associate with the cytoplasmic domains of several members of the CD2 subfamily of cell surface receptors, including SLAM, 2B4, and CD84. While recruitment of SAP to SLAM occurred in a phosphorylation-independent manner, SAP was found to bind preferentially to tyrosine-phosphorylated cytoplasmic domains within 2B4 and CD84. Missense or nonsense mutations in the SAP open reading frame were identified in five of seven clinically diagnosed XLP patients from different kindreds. Four of these variants retained the ability to bind to the cytoplasmic tails of SLAM and CD84. While ectopic expression of wild-type SAP was observed to block the binding of SHP-2 to SLAM, mutant SAP derivatives that retained the ability to bind SLAM did not inhibit recruitment of SHP-2 to SLAM. In contrast, SAP binding to CD84 had no effect on the ability of CD84 to recruit SHP-2, but instead displaced SHP-1 from the cytoplasmic tail of CD84. These results suggest that mutations in the gene encoding the XLP protein SAP lead to functional defects in the protein that include receptor binding and SHP-1 and SHP-2 displacement and that SAP utilizes different mechanisms to regulate signaling through the CD2 family of receptors.

Antigens, CD↗