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Biomedical subjects

L Nicholson

Publications and source records attributed to L Nicholson.

At least 19 recordsLinked to original sources
PubMed2000

IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is induced in the SJL/J mouse by adoptive transfer of activated proteolipid protein peptide (PLP) 139-151-specific Th1 cells. T cells responding to altered peptide ligands (APL) of PLP, previously shown to induce Th2 differentiation and regulate disease in PLP-immunized mice, do not transfer EAE. However, the exact mechanism of disease regulation by APL-specific T cells has not been elucidated. In this report, we show that 1F1, a Th2 clone specific for an APL of PLP139-151 can prevent adoptive transfer of EAE when cocultured with PLP-encephalitogenic spleen cells (PLP-spleen). Cytokines from activated 1F1 cells were detected by hybridization of mRNA to oligonucleotide arrays (DNA chip) and by ELISA. The Th2 cytokines found to be present at the highest protein and mRNA levels were evaluated for their role in suppression of adoptive transfer of EAE from PLP-activated spleen cell cultures. Abs to individual cytokines in 1F1 PLP-spleen cocultures suggested that IL-4, IL-13, and TGF-beta played a significant role in suppressing EAE. Abs to the combination of IL-4, IL-10, IL-13, and TGF-beta completely neutralized the protective effect of 1F1. Addition of Th2 cytokines to PLP-spleen cultures showed that IL-13 and TGF-beta were each individually effective and low levels of IL-4 synergized with IL-13 to inhibit disease transfer. IL-5, IL-9, and IL-10 had little or no effect whereas GM-CSF slightly enhanced EAE. Our results demonstrate that Th2 cytokines derived from APL-specific Th2 cells can effectively down-regulate the encephalitogenic potential of PLP-spleen cells if present during their reactivation in culture.

Adoptive Transfer↗
PubMed2000

RANTES binding and down-regulation by a novel human herpesvirus-6 beta chemokine receptor.

The human herpesvirus 6 (HHV-6) U51 gene defines a new family of betaherpesvirus-specific genes encoding multiple transmembrane glycoproteins with similarity to G protein-coupled receptors, in particular, human chemokine receptors. These are distinct from the HHV-6 U12 and HCMV US28 family. In vitro transcription and translation as well as transient cellular expression of U51 showed properties of a multiple transmembrane protein with a 30-kDa monomer as well as high m.w. aggregates or oligomers. Transient cellularly expressed U51 also appeared to form dimeric intermediates. Despite having only limited sequence similarity to chemokine receptors, U51 stably expressed in cell lines showed specific binding of the CC chemokine RANTES and competitive binding with other beta chemokines, such as eotaxin; monocyte chemoattractant protein 1, 3, and 4; as well as the HHV-8 chemokine vMIPII. In epithelial cells already secreting RANTES, U51 expression resulted in specific transcriptional down-regulation. This correlated with reduced secretion of RANTES protein into the culture supernatants. Regulation of RANTES levels may alter selective recruitment of circulating inflammatory cells that the virus can infect and thus could mediate the systemic spread of the virus from initial sites of infection in epithelia. Alternatively, chemokine regulation could modulate a protective inflammatory response to aid the spread of virus by immune evasion. Such mimicry, by viral proteins, of host receptors leading to down-regulation of chemokine expression is a novel immunomodulatory mechanism.

Amino Acid Sequence↗
PubMed2000

Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.

Animals↗
PubMed2000

Use of a dry latex agglutination test to measure eradication of Helicobacter pylori infection.

BACKGROUND AND METHODS: A total antibody latex serology test was compared with enzyme immunoassay serology after treatment for Helicobacter pylori infection in 22 patients. RESULTS: Nineteen patients were cured of infection, but only nine (47%) were negative by the latex test after 6 months. However a significant decline in immunoglobulin (Ig)G was seen in 90% of the cured patients. CONCLUSIONS: Although the latex test is suitable for initial diagnosis of H. pylori infection, it is not suitable for monitoring treatment success. A decline in IgG of more than 40% correlates well with successful eradication of H. pylori.

Anti-Bacterial Agents↗
PubMed2000

Magnitude estimation of manually assessed elastic stiffness: stability of the exponent.

Magnitude estimations were obtained for manual assessments of pure elastic stiffness stimuli (metal springs). 20 subjects of varied experience in manual assessment of spinal stiffness volunteered to participate. The mean exponent of the power function relating perceived magnitude of elastic stiffness to measured physical magnitude was 1.65. Exponents varied across the 20 individuals but were stable across testing sessions held at least 2 weeks apart, and the size of the exponent was not related to prior experience.

Adult↗
PubMed1999

Novel, nonconsensus cellular splicing regulates expression of a gene encoding a chemokine-like protein that shows high variation and is specific for human herpesvirus 6.

There are few genes that are specific and diagnostic for human herpesvirus-6. U83 and U22 are two of them. U22 is unique, whereas U83 encodes distant similarity with some cellular chemokines. Reverse transcription-polymerase chain reaction, cDNA cloning, and sequence analyses show polyadenylated RNA transcripts corresponding to minor full-length and abundant spliced forms of U83 in human herpesvirus 6-infected cells. The splice donor and acceptor sites do not fit consensus sequences for either major GT-AG or minor AT-AC introns. However, the spliced form can also be detected in a U83 transfected cell line; thus the novel sites are used by cellular mechanisms. This intron may represent a new minor CT-AC splicing class. The novel splicing regulates gene expression by introducing a central stop codon that abrogates production of the chemokine-like molecule, resulting in an encoded truncated peptide. The use of metabolic inhibitors and an infection time course showed expression of the two RNA transcripts with immediate early kinetics. However, the full-length product accumulated later, dependent on virus DNA replication, similar to U22. Sequence analyses of 16 strains showed high variation (13%) in U83, with conservation of the novel splice sites. Representative strain variants had similar kinetics of expression and spliced products.

3' Untranslated Regions↗
PubMed1999

Comparison of five methods used to determine low back disorder risk in a manufacturing environment.

STUDY DESIGN: Five methods for quantifying work-related low back disorder (LBD) risk were used to assess 178 autoworkers from 93 randomly selected production jobs. OBJECTIVE: To determine if five occupational LBD risk evaluation methods yielded similar assessments of manual material handling tasks. SUMMARY OF BACKGROUND DATA: Several techniques are available for quantifying LBD risk in the workplace and are used in industry for job evaluation and redesign. It is unknown whether the methods yield similar results. METHODS: The five job evaluation methods were the 1993 National Institute for Occupational Safety and Health model, the Static Strength Prediction Program, the Lumbar Motion Monitor model, and two variations of the United Auto Workers (UAW)-General Motors Ergonomic Risk Factor Checklist. These methods were selected because they represent common practice within the automotive industry, the result of governmental efforts to protect the workforce, or models thought to be the most scientifically advanced. RESULTS: Intercorrelations between methods ranged between 0.21 and 0.80. Pairwise analysis of risk group classifications identified biases on the part of the National Institute for Occupational Safety and Health equation, which considered jobs to be of higher risk relative to other methods, and on the part of the Static Strength Prediction Program, which considered nearly all the jobs sampled to be low risk. CONCLUSIONS: There is little agreement among the five quantitative ergonomic analysis methods used. In part, this may be because of their differential focus on acute versus cumulative trauma, thereby suggesting that greater consideration needs to be given to the underlying causes of LBD within a facility before selecting an ergonomic evaluation method.

Ergonomics↗
PubMed1999

Hypercalciuria and urolithiasis in a case of Costello syndrome.

Costello syndrome is characterized by postnatal growth deficiency, mental retardation, curly hair, coarse characteristic face, and loose skin of hands and feet. Patients with this syndrome have a high incidence of cardiac involvement, including arrhythmia, atrial septal defect, and hypertrophic cardiomyopathy. We report a 16-year-old adolescent female with Costello syndrome who presents with hypercalciuria and urolithiasis.

Abnormalities, Multiple↗
PubMed1999

Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies.

We investigated the suitability of transformed rice cell lines as a system for the production of therapeutic recombinant antibodies. Expression constructs encoding a single-chain Fv fragment (scFvT84.66, specific for CEA, the carcinoembryonic antigen present on many human tumours) were introduced into rice tissue by particle bombardment. We compared antibody production levels when antibodies were either secreted to the apoplast or retained in the endoplasmic reticulum (ER) using a KDEL retention signal. Production levels were up to 14 times higher when antibodies were retained in the ER. Additionally, we compared construct sencoding different leader peptides (plant codon optimised murine immunoglobulin heavy and light chain leader peptides from mAb24) and carrying alternative 5' untranslated regions (the petunia chalcone synthase gene 5' UTR and the tobacco mosaic virus omega sequence). We observed no significant differences in antibody production levels among cell lines transformed with these constructs. The highest level of antibody production we measured was 3.8 micrograms g-1 callus (fresh weight). Immunological analysis of transgenic rice callus confirmed the presence of functional scFvT84.66. We discuss the potential merits of cell culture for the production of recombinant antibodies and other valuable macromolecules.

5' Untranslated Regions↗
PubMed1998

Prevalence of Helicobacter pylori in a representative Anglo-Celtic population of urban Melbourne.

The aims of this study were to assess the prevalence of Helicobacter pylori and its relationship with different epidemiological factors in an Anglo-Celtic Australian population in the Melbourne urban area. Two hundred and seventy-three (120 men and 153 women with a mean age of 55.6 and range of 20 to 80 years) of 396 eligible subjects randomly sampled from the telephone directory were studied. An ELISA technique was used to detect H. pylori immunoglobulin (Ig)G antibody and self-administered questionnaires were completed. The overall seroprevalence of H. pylori was 38% and increased with age from 18% (20-30 years old) to 53% (over 70 years; P < 0.0001). The acquisition of H. pylori infection was 1% per year. The prevalence of H. pylori was 48% in men and 30% in women (P < 0.01). The frequency of H. pylori was also associated with low-income levels and current smoking, but was not associated with peptic ulcer disease history. The prevalence of H. pylori infection in a representative Australian population was found to be similar to other developed countries. The risk factors for H. pylori infection include age, male sex, low household income and a smoking habit. No correlation between H. pylori status and dyspepsia symptoms were observed.

Adult↗
PubMed1998

The prevalence of Helicobacter pylori in practising dental staff and dental students.

Recent studies suggest Helicobacter pylori is spread by faecal-oral or oral-oral transmission. Gastroenterologists who are exposed to gastric secretions and saliva have a high prevalence of H. pylori infection. Venous blood was obtained from 92 dentists, 40 dental nurses, 33 fifth year and 30 first year dental students. An ELISA assay was used to detect H. pylori IgG antibodies. Results were compared with an age and sex matched normal population. The prevalence of H. pylori infection in dentists, dental nurses, fifth year dental students and first year dental students were 23 per cent, 18 per cent, 18 per cent and 16 per cent, respectively. There were no significant differences when compared with the normal population controls. The prevalence of H. pylori antibody was not significantly increased with years of practice or patient contact time in dentists and dental nurses. Helicobacter pylori infection is uncommon in dental professionals working in the oral cavity.

Adolescent↗
PubMed1997

Extended survival in a new case of ter Haar syndrome: further delineation of the syndrome.

We present a boy followed from age 5-13 years who is the fifth reported case of ter Haar syndrome. This is a recently-named entity comprising congenital glaucoma, hypertelorism, congenital heart defects and kyphoscoliosis, skeletal dysplasia, and developmental delay. These patients were originally thought to have an autosomal-recessive form of Melnick-Needles syndrome, and were only identified as having a distinct syndrome with the report of the fourth case. Probable autosomal-recessive inheritance is based on consanguinity in 4 of 5 cases. Ocular, cardiac, and craniofacial findings distinguish ter Haar syndrome as a distinct entity. Our patient is the longest survivor at present, suggesting that there is heterogeneity in this syndrome or, alternatively, that aggressive therapy of the congenital heart defects has significant effect.

Abnormalities, Multiple↗
PubMed1997

Lateral meningocele syndrome: three new patients and review of the literature.

One female and two male patients with multiple lateral meningoceles are presented. They do not have neurofibromatosis or Marfan syndrome and share findings with the two previously described patients with multiple lateral meningoceles. The original report by Lehman et al. [1977: J Pediatr 90:49-54] was titled "familial osteosclerosis," because osteosclerosis was present in the proposita and her mother; the patient described by Philip et al. [1995: Clin Dysmorphol 4:347-351] also had increased bone density of the skull base and the sutures. Thickened calvaria were present in one of our patients; two had a prominent metopic suture. Other shared findings include multiple lateral meningoceles, Wormian bones, malar hypoplasia, downslanted palpebral fissures, a high narrow palate, and cryptorchidism in males. In addition, our patients showed ligamentous laxity, keloid formation, hypotonia, and developmental delay. A short umbilical cord was noted in two patients. One had a hypoplastic posterior arch of the atlas and an enlarged sella, as reported by Lehman et al. [1977]. Our patients appear to have the same syndrome as previously reported. We suggest it be called "lateral meningocele syndrome," because of this unique finding.

Abnormalities, Multiple↗
PubMed1997

Chiari malformation and tonsillar ectopia in twin brothers and father with autosomal dominant spondylo-epiphyseal dysplasia tarda.

We describe twin brothers and father with autosomal dominant spondylo-epiphyseal dysplasia (SED) tarda. The proband presented at 17 years with nystagmus and esotropia due to a severe Chiari malformation. A milder, asymptomatic Chiari I malformation was seen in his brother and tonsillar ectopia in his father. Although these malformations have not been described in patients with SED, they are relatively common in other bony abnormalities, particularly those involving the cranio-cervical junction. The concordance of the Chiari malformations or tonsillar ectopia in all three family members with SED suggests that this association is not coincidental. It seems possible that the downward displacement of the cerebellum occurs secondary to primary osseous abnormality, rather than due to a primary disturbance of embryological development. The lack of additional brain malformations in our patients is consistent with this theory.

Adolescent↗
PubMed1997

Transfer index of multiple angulated abutments in the restoration of an edentulous maxilla.

Osseointegration and the replacement of missing dentition with endosseous implants is a viable alternative to conventional prosthodontics with good long-term prognosis. This article describes a procedure for fabricating an index to accurately transfer the ideal position of several 17-degree angulated abutments from the master cast to the mouth in a predictable way. After the final try-in, evaluation of the space available and angulation of the implants is made to choose the appropriate abutments within the contours of the final restoration. A customized index was also developed to accurately transfer the position of those 17-degree angulated abutments from the master cast to the mouth in a precise manner.

Dental Abutments↗
PubMed1997

Evaluating large scale health information systems: from practice towards theory.

With the introduction of large scale health information systems which are incrementally developed from legacy systems, evaluators are faced with difficult methodological and practical problems. Some of the problems involved in multidisciplinary multi-method evaluations care discussed. It is argued that the development of a framework for evaluation is necessary in order to successfully plan an evaluation, understand the implications of the results and make future predictions based upon them. Some suggestions for arriving at such a framework are put forward.

Evaluation Studies as Topic↗