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L Harrison

Publications and source records attributed to L Harrison.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cysticercosis: towards the design of a diagnostic kit based on synthetic peptides.

Cysticercosis caused by Taenia solium is a very common disease in developing countries that seriously affects human health. Diagnosis can only be confirmed with the aid of computerized tomography or nuclear magnetic resonance (NMR) creating obvious difficulties for epidemiological studies. Reliable immunoassays employing cerebrospinal fluid (CSF) have been developed, based on the use of cysticercal antigens. However, the reliance on parasite material is restrictive. Herein, we report the advances in the design of a diagnostic kit based on immunodominant synthetic peptides, targeting four candidate epitopes KETc1, KETc12, 410 and 413 which were identified from three different clones (KETc1, 12 and 4) selected from a cDNA library of Taenia crassiceps. CSF antibodies against T. solium cysticercal antigens (TCA) as well as the four peptides were determined by enzyme-linked immunoabsorbent assays (ELISA) using two panels of CSF from patients with confirmed neurocysticercosis and other neurological diseases. In the first CSF panel which included patients with high level of antibodies against TCA, KETc12 exhibited almost the same sensitivity (87.5%) as TCA (93.7%) and 100% specificity. In the second panel of 110 CSF collected at random, two peptides (KETc1 and KETc12) exhibited sensitivities of 40 and 36% respectively, and were 100% specific.

Animals↗
PubMed2000

Functional and quality-of-life outcomes in patients with rectal cancer after combined modality therapy, intraoperative radiation therapy, and sphincter preservation.

PURPOSE: Locally advanced primary and recurrent rectal cancers treated with external beam radiation therapy, intraoperative radiation therapy, and chemotherapy represent a complex group of patients in the setting of extensive pelvic surgery and sphincter preservation. We sought to define functional outcome and quality of life in this subset of patients. METHODS: We retrospectively reviewed our experience with locally advanced primary and recurrent rectal cancer patients who underwent intraoperative radiation therapy with either low anterior resection (n = 12) or coloanal anastomosis (n = 6) between 1991 and 1998. Current functional outcome and quality of life were evaluated by a detailed questionnaire. RESULTS: Median time from operation to assessment was 24 (range, 6-93) months. Using a standardized Sphincter Function Scale, incorporating the number of bowel movements per day and degree of incontinence, patients were graded as poor, fair, good, or excellent function. Of all patients, 56 percent reported unfavorable (poor or fair) function. Of the subset of patients with coloanal anastomosis or very low low anterior resection, 88 percent had unfavorable function as compared with 30 percent with standard low anterior resection. (P = 0.02; Fisher's exact probability test). A quality-of-life satisfaction score based on social, professional, and recreational restrictions demonstrated 56 percent of patients to be dissatisfied with their bowel function. CONCLUSIONS: The majority of patients with advanced rectal cancers who require external beam radiation therapy, extensive pelvic surgery, and intraoperative radiation therapy report unfavorable functional and quality-of-life outcomes after sphincter preservation. In this setting patients being considered for coloanal anastomosis or very low anterior resection may be better served by permanent diversion.

Adult↗
PubMed2000

Tumor necrosis factor alpha and interleukin 1beta up-regulate gastric mucosal Fas antigen expression in Helicobacter pylori infection.

Fas-mediated gastric mucosal apoptosis is gaining attention as a cause of tissue damage due to Helicobacter pylori infection. We explored the effects of H. pylori directly, and the effects of the inflammatory environment established subsequent to H. pylori infection, on Fas-mediated apoptosis in a nontransformed gastric mucosal cell line (RGM-1). Exposure to H. pylori-activated peripheral blood mononuclear cells (PBMCs), but not H. pylori itself, induced Fas antigen (Fas Ag) expression, indicating a Fas-regulatory role for inflammatory cytokines in this system. Of various inflammatory cytokines tested, only interleukin 1beta and tumor necrosis factor alpha induced Fas Ag expression, and removal of either of these from the conditioned medium abrogated the response. When exposed to Fas ligand, RGM-1 cells treated with PBMC-conditioned medium underwent massive and rapid cell death, interestingly, with a minimal effect on total cell numbers early on. Cell cycle analysis revealed a substantial increase in S phase cells among cells exposed to Fas ligand, suggesting an increase in their proliferative response. Taken together, these data indicate that the immune environment secondary to H. pylori infection plays a critical role in priming gastric mucosal cells to undergo apoptosis or to proliferate based upon their Fas Ag status.

Animals↗
PubMed2000

Comparison of service member and military spouse satisfaction with installation fitness facilities and exercise programs.

Satisfaction with fitness facilities has long been accepted as a positive contributing factor to physical activity, readiness, and overall quality of life for military families. Our findings are based on a random sample of military families surveyed at 38 installations worldwide and at remote locations. A total of 8,572 service member and 3,493 spouse (55% and 32% response rate, respectively) questionnaires were completed and returned. Overall, members were satisfied with fitness facilities and programs, but spouses were less satisfied and more unfamiliar with these facilities. Most valued programs were fitness centers and swimming pools. Members reported that elimination of fitness facilities would greatly decrease the quality of life on installations, particularly at sites outside the continental United States, whereas spouses reported that this would not have a dramatic effect. The results of this study could be used to direct funding allocations, improve the health and fitness of military families, and suggest areas for further research.

Adult↗
PubMed1999

In vitro repair of synthetic ionizing radiation-induced multiply damaged DNA sites.

When ionizing radiation traverses a DNA molecule, a combination of two or more base damages, sites of base loss or single strand breaks can be produced within 1-4 nm on opposite DNA strands, forming a multiply damaged site (MDS). In this study, we reconstituted the base excision repair system to examine the processing of a simple MDS containing the base damage, 8-oxoguanine (8-oxoG), or an abasic (AP) site, situated in close opposition to a single strand break, and asked if a double strand break could be formed. The single strand break, a nucleotide gap containing 3' and 5' phosphate groups, was positioned one, three or six nucleotides 5' or 3' to the damage in the complementary DNA strand. Escherichia coli formamidopyrimidine DNA glycosylase (Fpg), which recognizes both 8-oxoG and AP sites, was able to cleave the 8-oxoG or AP site-containing strand when the strand break was positioned three or six nucleotides away 5' or 3' on the opposing strand. When the strand break was positioned one nucleotide away, the target lesion was a poor substrate for Fpg. Binding studies using a reduced AP (rAP) site in the strand opposite the gap, indicated that Fpg binding was greatly inhibited when the gap was one nucleotide 5' or 3' to the rAP site. To complete the repair of the MDS containing 8-oxoG opposite a single strand break, endonuclease IV DNA polymerase I and Escherichia coli DNA ligase are required to remove 3' phosphate termini, insert the "missing" nucleotide, and ligate the nicks, respectively. In the absence of Fpg, repair of the single strand break by endonuclease IV, DNA polymerase I and DNA ligase occurred and was not greatly affected by the 8-oxoG on the opposite strand. However, the DNA strand containing the single strand break was not ligated if Fpg was present and removed the opposing 8-oxoG. Examination of the complete repair reaction products from this reaction following electrophoresis through a non-denaturing gel, indicated that a double strand break was produced. Repair of the single strand break did occur in the presence of Fpg if the gap was one nucleotide away. Hence, in the in vitro reconstituted system, repair of the MDS did not occur prior to cleavage of the 8-oxoG by Fpg if the opposing single strand break was situated three or six nucleotides away, converting these otherwise repairable lesions into a potentially lethal double strand break.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Invariant or highly conserved TCR alpha are expressed on double-negative (CD3+CD4-CD8-) and CD8+ T cells.

TCR alpha (TCRA) expression was examined in RNA samples from PBMC and isolated populations of CD4+, CD8+, and DN T cells from 15 healthy individuals. The expressed TCR repertoire was surveyed using spectratype analysis, a technique that displays the distribution of complementarity determining region 3 (CDR3) lengths for each TCRAV gene family. The results revealed the presence of unusual populations of double-negative (DN; CD4-CD8-CD3+) T cells that express invariant or conserved TCRAV4A, AV7, AV19, and AV24 chains. Each of the conserved TCRA families was over-represented in >70% of the individuals studied, and all individuals expressed at least one of the over-represented TCRAV families. Over-represented conserved AV4A or AV7 sequences were also present in CD8+ T cells from most donors. The extent of TCRA sequence conservation is unparalleled. TCRAV4A, AV19, and AV24 sequences were invariant, although AV4A and AV19 transcripts contained N region additions. TCRAV24 transcripts derived from the direct juxtaposition of V and J gene segments. TCRAV7 sequences showed some diversity in two amino acids encoded at junctions of V and J gene segments. Although derivation of DN T cells with conserved TCRA chains is puzzling, the wide-spread expression of these unusual cells suggests an important function.

Adult↗
PubMed1999

A randomized trial comparing 5-mg and 10-mg warfarin loading doses.

BACKGROUND: Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio (INR). Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state; they also may not hasten achieving an INR value between 2.0 and 3.0. This study was designed to prospectively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy. METHODS: Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were randomly allocated to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses were based on dosing algorithms. The INR was measured daily for 5 days. The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3, 4, or 5 of the study and whose INR did not exceed 3.0 at any point during the study. RESULTS: Five (24%) of 21 patients in the 10-mg group and 21 (66%) of 32 patients in the 5-mg group achieved the primary end point (relative risk 2.22, 95% confidence interval 1.30-3.70 [P < .003]). A trend toward less overanticoagulation was seen in the 5-mg warfarin group. CONCLUSION: A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy.

Aged↗
PubMed1999

Do the rich really die young? Alcohol-related mortality and social class in Great Britain, 1988-94.

AIMS: To determine whether social class is a major influence on alcohol-related mortality in the general, economically active population of Great Britain. DESIGN AND PARTICIPANTS: Poisson regression of rates of mortality known to be directly caused by alcohol consumption by age, sex and social class in England, Wales and Scotland. MEASUREMENTS: The measure of alcohol-related mortality is total deaths from ICD-9 categories 291; 303; 357.5; 425.5; 535.3; 305; 790.3; and 571.0-571.3 over the 7-year period 1988-94. (It excludes deaths for which alcohol-attributable fractions would need to be calculated.) The measure of social class is the British Registrar General's six-fold occupational classification, used to code census and death certification data. FINDINGS: Alcohol-related mortality rates are higher for men in the manual occupations than in the non-manual occupations, but the relative magnitude depends on age. Men aged 25-39 in the unskilled manual class are 10-20 times more likely to die from alcohol-related causes than those in the professional class, whereas men aged between 55 and 64 in the unskilled manual class are only about 2.5-4 times more likely to die. For women in paid employment there is no consistent class gradient; younger women in the manual classes are more likely to die from alcohol-related causes, but for older women it is those in the professional class who suffer elevated mortality. CONCLUSIONS: Social class is a risk factor for alcohol-related mortality in Britain, although it is mediated by age and sex. Alcohol appears to be similar to other psychoactive substances, therefore, in that problem use is linked to social structural factors such as poverty, disadvantage and social class. This suggests that social interventions aimed at reducing poverty and inequality have the potential to reduce current levels of alcohol-related harm among the poorest groups in the community.

Adolescent↗
PubMed1999

Radiographic grading for knee osteoarthritis. A revised scheme that relates to alignment and deformity.

OBJECTIVE: To develop a radiographic grading scheme for osteoarthritis of the knee that would relate to arthritic progression and deformity. METHODS: The scheme of Scott, et al was revised to include new fields of Tibial Erosion and Subluxation; the fields of Tibial Osteophytes and Sclerosis were removed. The worst affected compartment only was scored on frontal Standardized Knee Images, which were used to define knee alignment variables. RESULTS: The interreader reliability (kappa = 0.92) and correlation for total scores (r = 0.94) were both excellent (p < 0.001). Individual field scores and total knee scores both correlated well with most limb alignment variables, especially the hip-knee-ankle angle (r = 0.77, p < 0.001). CONCLUSION: These findings encourage further evaluations for outcome measurement, diagnostic sensitivity, and sensitivity to define arthritic change over time.

Arthroscopy↗
PubMed1998

Tsetse thrombin inhibitor: bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans.

The tsetse thrombin inhibitor, a potent and specific low molecular mass (3,530 Da) anticoagulant peptide, was purified previously from salivary gland extracts of Glossina morsitans morsitans (Diptera: Glossinidae). A 303-bp coding sequence corresponding to the inhibitor has now been isolated from a tsetse salivary gland cDNA library by using degenerate oligonucleotide probes. The full-length cDNA contains a 26-bp untranslated segment at its 5' end, followed by a 63-bp sequence corresponding to a putative secretory signal peptide. A 96-bp segment codes for the mature tsetse thrombin inhibitor, whose predicted molecular weight matches that of the purified native protein. Based on its lack of homology to any previously described family of molecules, the tsetse thrombin inhibitor appears to represent a unique class of naturally occurring protease inhibitors. Recombinant tsetse thrombin inhibitor expressed in Escherichia coli and the chemically synthesized peptide are both substantially less active than the purified native protein, suggesting that posttranslational modification(s) may be necessary for optimal inhibitory activity. The tsetse thrombin inhibitor gene, which is present as a single copy in the tsetse genome, is expressed at high levels in salivary glands and midguts of adult tsetse flies, suggesting a possible role for the anticoagulant in both feeding and processing of the bloodmeal.

Amino Acid Sequence↗
PubMed1998

The treatment of malignant mesothelioma with a gene modified cancer cell line: a phase I study.

Malignant mesothelioma is a tumor of the pleura for which there is no satisfactory treatment. It is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalities is superior to no treatment at all. Because of the dismal prognosis for patients with malignant mesothelioma, a new mode of treatment is desperately needed. A promising area of research into the treatment of various malignancies is gene therapy. Recent studies have demonstrated the utility of exposing tumor cells to cells transduced to express the Herpes simplex virus gene for thymidine kinase (HSV-tk). By virtue of their expression of HSV-tk, the transduced cells are rendered susceptible to the antiviral drug, ganciclovir (GCV). and nearby tumor cells are killed by a phenomenon termed the bystander effect. In this protocol we propose a Phase I trial to study the safety and determine the maximal tolerated dose of an HSV-tk-transduced ovarian cancer cell line (PA1-STK cells) infused into the pleural cavities of patients with malignant pleural mesothelioma, followed by systemic administration of ganciclovir. The hope is that administration of ganciclovir will result in killing of the HSV-tk transduced ovarian cancer cells as well as the nearby malignant mesothelioma cells. This is a standard dose-escalation protocol.

Clinical Protocols↗
PubMed1998

Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin.

BACKGROUND: Low-molecular-weight (LMW) heparins are safe and effective for out-of-hospital treatment of acute deep-vein thrombosis (DVT) in a clinical trial setting. We examined the efficacy, safety, and feasibility of home treatment with LMW heparin of consecutive eligible patients with acute DVT in a routine care setting. In addition, we report our experience with patient compliance, acceptance, and satisfaction. METHODS: We performed a prospective cohort study of consecutive patients presenting to 2 thromboembolism clinics in a large Ontario city. Eligible patients were treated with LMW heparin for a minimum of 5 days and with long-term warfarin sodium. Outcomes included the incidences of bleeding and recurrence of DVT and pulmonary embolism and patient satisfaction as determined by a questionnaire. RESULTS: One hundred thirteen patients with objectively confirmed DVT underwent screening; 89 patients were treated at home with LMW heparin. During the study, 1 patient died of a combination of pulmonary embolism and major bleeding, another patient required admission to the hospital for bleeding, and 5 patients with active malignant disease had recurrent DVT. Of the patients who completed the satisfaction questionnaire, 75 (91%) of 82 were pleased with home treatment; 44 (70%) of 63 felt comfortable self-injecting the LMW heparin; and 71 (92%) of 77 were satisfied with the support and instruction they received during the outpatient treatment. CONCLUSIONS: Outpatient treatment of DVT with LMW heparin is safe, effective, and feasible for most patients and is associated with a high degree of patient satisfaction.

Adult↗
PubMed1998

Diagnosis of porcine cysticercosis: a comparative study of serological tests for detection of circulating antibody and viable parasites.

Epidemiological studies of porcine cysticercosis require identification of pigs harbouring viable Taenia solium cysticerci and estimates of the degree of exposure to the parasite in the pig population destined for human consumption. Identification of infected pigs with viable larvae is achieved through detection of their secretory products. However, detectable levels of circulating antibody may also be present in the absence of viable larvae. In this study, both types of tests have been evaluated in groups of pigs experimentally infected with T. solium. Detection of viable cysticerci was achieved using a monoclonal antibody-based (HP10) antigen capture assay. HP10 epitope-bearing antigens have now been demonstrated in T. solium and T. crassiceps cyst fluid and excretion/secretions. Serum antibodies were measured in ELISA assays using two parasite preparations as antigens; T. solium cyst fluid and T. crassiceps cyst fluid antigens bearing the HP10 epitope. Low-background values were obtained with sera from non-infected animals in all the assays used. In heavily infected pigs, both antigens and antibodies were detected at least 29 days and up to 200 days post-infection (pi), while in lightly infected pigs antigen and antibodies were first observed between 61-97 days pi. Thus, the levels of the serum antigen and antibody varied with the intensity of the infection.

Animals↗
PubMed1998

Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules.

Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly with respect to TAP affinities of their ligands. As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.

ATP-Binding Cassette Transporters↗
PubMed1998

Multiply damaged sites in DNA: interactions with Escherichia coli endonucleases III and VIII.

Bursts of free radicals produced by ionization of water in close vicinity to DNA can produce clusters of opposed DNA lesions and these are termed multiply damaged sites (MDS). How MDS are processed by the Escherichia coli DNA glycosylases, endonuclease (endo) III and endo VIII, which recognize oxidized pyrimidines, is the subject of this study. Oligonucleotide substrates were constructed containing a site of pyrimidine damage or an abasic (AP) site in close proximity to a single nucleotide gap, which simulates a free radical-induced single-strand break. The gap was placed in the opposite strand 1, 3 or 6 nt 5' or 3' of the AP site or base lesion. Endos III and VIII were able to cleave an AP site in the MDS, no matter what the position of the opposed strand break, although cleavage at position one 5' or 3' was reduced compared with cleavage at positions three or six 5' or 3'. Neither endo III nor endo VIII was able to remove the base lesion when the gap was positioned 1 nt 5' or 3' in the opposite strand. Cleavage of the modified pyrimidine by endo III increased as the distance increased between the base lesion and the opposed strand break. With endo VIII, however, DNA breakage at the site of the base lesion was equivalent to or less when the gap was positioned 6 nt 3' of the lesion than when the gap was 3 nt 3' of the lesion. Gel mobility shift analysis of the binding of endo VIII to an oligonucleotide containing a reduced AP (rAP) site in close opposition to a single nucleotide gap correlated with cleavage of MDS substrates by endo VIII. If the strand break in the MDS was replaced by an oxidized purine, 7,8-dihydro-8-oxoguanine (8-oxoG), neither endo VIII cleavage nor binding were perturbed. These data show that processing of oxidized pyrimidines by endos III and VIII was strongly influenced by the position and type of lesion in the opposite strand, which could have a significant effect on the biological outcome of the MDS lesion.

Base Sequence↗
PubMed1998

"When you carry condoms all the boys think you want it": negotiating competing discourses about safe sex.

With the advent of HIV, sexual health campaigns and formal sex education in schools have worked to instil the concept of safe sex into the collective minds of Australia's youth. However the concept in its present guise is a fairly limited one. We argue in this paper that the predominant emphasis in education programmes on safe sex as condom use may be counter-productive for some young heterosexuals for two reasons. First, this strategy is male-focused and may not extrapolate well to young women who face special risks around pregnancy and rigid societal gender norms which govern sexual behaviour. Second, health promotion strategies aimed at young heterosexuals are based on an assumption of rational decision-making in sexual encounters and obscure the non-rational nature of arousal and desire, and the unequal power relations that exist between young men and women engaging in sex. Five hundred and twelve senior rural students participated in the study which included group discussions about sexuality and survey items which focused on the meanings of safe sex and the accessibility and use of condoms. The results showed that though most students identified condoms with safe sex, many were ambivalent about using them. Reasons given related to problems of negotiation, difficulties of access, and the risks which condoms gave no protection from, such as a sullied reputation. Perhaps, partly because of this, some students were looking to less secure methods of protection such as informal history-taking and monogamy. It is argued that successful sexual health promotion strategies must address the broad spectrum of concerns facing young men and women when they become sexually active and that consideration be given to the social context in which young people conduct their sexual lives.

Adolescent↗