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Biomedical subjects

C Hooper

Publications and source records attributed to C Hooper.

At least 19 recordsLinked to original sources

Proteome-based plasma biomarkers for Alzheimer's disease.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

Aged↗

Haemophilia A in a litter of Siberian huskies.

AIM: To investigate haemorrhagic diathesis in several males in a litter of Siberian huskies. METHODS: Activated partial thromboplastin time, prothrombin time, and Factor VIII and Factor IX concentrations were measured in citrated whole blood samples. RESULTS: Males in the litter had decreased Factor VIII concentrations. CONCLUSIONS: Haemophilia A was diagnosed as the cause of haemorrhagic diathesis in several males in a litter of Siberian huskies.

Journal Article↗

The frequency of breast screening in older women.

Increasing age is the main risk of breast cancer in women. Screening mammograms are effective in women aged over 65 years for the early detection of breast cancer. Older women's health beliefs affect their use of mammogram screening and they tend not to take advantage of screening opportunities. Nurses must discuss the benefits of screening mammograms with their older clients.

Aged↗

Poxvirus dilemmas.

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Contraindications↗

Development of an alcohol withdrawal clinical pathway: an interdisciplinary process.

Studies show that as many as 40 percent of all patients in general hospitals are admitted because of complications related to alcoholism. However, the literature has little in specific clinical pathways, treatment protocols, or guidelines for the interdisciplinary care of these patients in the acute care setting. Furthermore, the little information that is published shows a lack of consistency in recommended treatment regimes. This article reviews a coordinated, interdisciplinary effort in developing and implementing a clinical pathway for alcohol withdrawal.

Alcoholic Beverages↗

A survey of computer technology utilization in school nursing.

Computer technology offers a solution to problems associated with paper-based health records. The purposes of this descriptive study were to identify the utilization of and support for computer technology in managing student health data and documenting school nurse practice. Findings from a sample of school nurse respondents to the Computer Technology and School Nursing Survey (CTSNS) indicated that of the 65% that used computers, nearly two-third used computers for three years or less. Although there was an increase in computer use when compared with an earlier study, more training, financial support, and research are needed for optimal utilization of computer technology.

Attitude of Health Personnel↗

Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group.

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, combined treatment with several agents may increase the effectiveness of antiviral therapy. We studied the safety and efficacy of saquinavir, an HIV-protease inhibitor, given with one or two nucleoside antiretroviral agents, as compared with the safety and efficacy of a combination of two nucleosides alone. METHODS: In this double-blind trial, patients with HIV infection were randomly assigned to receive either saquinavir (1800 mg per day) plus both zidovudine (600 mg per day) and zalcitabine (2.25 mg per day) or zidovudine plus either saquinavir or zalcitabine. The 302 patients enrolled had CD4+ counts of 50 to 300 cells per cubic millimeter and had previously received zidovudine for a median of 27 months. The study lasted 24 weeks, with an optional double-blind extension period of an additional 12 to 32 weeks. RESULTS: Ninety-six percent of the patients completed the 24-week study. In all three treatment groups, CD4+ cell counts rose at first and then fell gradually. The normalized area under the curve for the CD4+ count was greater with the three-drug combination than with either saquinavir and zidovudine (P=0.017) or zalcitabine and zidovudine (P<0.001). There were significantly greater reductions in plasma HIV with the three-drug combination than with the other regimens when peripheral-blood mononuclear cells were cultured for HIV and HIV RNA was assessed, and there were greater decreases in serum neopterin and beta2-microglobulin levels. There were no major differences in toxic effects among the three treatments. CONCLUSIONS: Treatment with saquinavir, zalcitabine, and zidovudine was well tolerated. This drug combination reduced HIV-1 replication, increased CD4+ cell counts, and decreased levels of activation markers in serum more than did treatment with zidovudine and either saquinavir or zalcitabine. Studies are warranted to evaluate whether the three-drug combination will reduce morbidity and mortality.

Adult↗

Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection. AIDS Clinical Trials Group (ACTG) 116B/117 Study Team. ACTG Virology Committee Resistance and HIV-1 RNA Working Groups.

Human immunodeficiency virus (HIV)-1 RNA level in plasma was evaluated as a surrogate marker for disease progression in a clinical trial of advanced HIV-1 infection. Baseline HIV-1 RNA level was an independent predictor of disease progression (relative hazard [RH] for each doubling of HIV-1 RNA level, 1.26; 95% confidence interval [CI], 1.03-1.54; P = .02), after adjusting for the week 4 change in HIV-1 RNA level, baseline CD4 cell count, syncytium-inducing phenotype, clinical status at study entry, and therapy randomization. A 50% reduction in HIV-1 RNA level was associated with a 27% decrease in the adjusted risk of disease progression during the study (RH, 0.73; 95% CI, 0.52-1.02; P = .07). The partial validation of HIV-1 RNA as a predictor for clinical end points has implications for the use of HIV-1 RNA in clinical trials and practice.

Acquired Immunodeficiency Syndrome↗

Immunogenicity and efficacy against lethal aerosol staphylococcal enterotoxin B challenge in monkeys by intramuscular and respiratory delivery of proteosome-toxoid vaccines.

Staphylococcal enterotoxin B (SEB), a primary cause of food poisoning, is also a superantigen that can cause toxic shock after traumatic or surgical staphylococcal wound [correction of would] infections or viral influenza-associated staphylococcal superinfections or when aerosolized for use as a potential biologic warfare threat agent. Intranasal or intramuscular (i.m.) immunization with formalinized SEB toxoid formulated with meningococcal outer membrane protein proteosomes has previously been shown to be immunogenic and protective against lethal respiratory or parenteral SEB challenge in murine models of SEB intoxication. Here, it is demonstrated that immunization of nonhuman primates with the proteosome-SEB toxoid vaccine is safe, immunogenic, and protective against lethal aerosol challenge with 15 50% lethal doses of SEB. Monkeys (10 per group) were primed i.m. and given booster injections by either the i.m. or intratracheal route without adverse side effects. Anamnestic anti-SEB serum immunoglobulin G (IgG) responses were elicited in all monkeys, but strong IgA responses in sera and bronchial secretions were elicited both pre- and post-SEB challenge only in monkeys given booster injections intratracheally. The proteosome-SEB toxoid vaccine was efficacious by both routes in protecting 100% of monkeys against severe symptomatology and death from aerosolized-SEB intoxication. These data confirm the safety, immunogenicity, and efficacy in monkeys of parenteral and respiratory vaccination with the proteosome-SEB toxoid, thereby supporting clinical trials of this vaccine in humans. The safety and enhancement of both bronchial and systemic IgA and IgG responses by the proteosome vaccine delivered by a respiratory route are also encouraging for the development of mucosally delivered proteosome vaccines to protect against SEB and other toxic or infectious respiratory pathogens.

Aerosols↗

Psychopharmacological treatment response of patients with a DSM-III diagnosis of dysthymic disorder.

In spite of its significant morbidity, dysthymic disorder has been under-researched, therefore effective treatment options are limited. This article presents data suggesting that dysthymia can be treated effectively with psychopharmacologic agents. A double-blind, placebo-controlled 7-week drug trial comparing imipramine to ritanserin, a serontonin-2 antagonist, indicated that both drugs were significantly more effective than placebo in alleviating dysthymia symptoms. Imipramine was slightly more effective than ritanserin, as indicated by ratings on the Hamilton Depression Rating Scale and the Zerssen Self-Rating Scale; however, imipramine also produced more side effects. On the basis of this study, we continued an open protocol for treating dysthymic patients with a specific serotonin reuptake inhibitor, fluoxetine. This open-label study indicated that fluoxetine was successful in reducing the dysthymia symptoms, particularly in the subaffective sub-type. These studies confirm the need for further research into the treatment options for patients suffering from dysthymia.

Adolescent↗

HTLV-I sequence in lymphoproliferative disorders.

Several recent studies reported the detection of partially deleted HTLV-I provirus in biopsies of lesions from patients with mycosis fungoides (MF) and T-cell anaplastic large-cell lymphoma. We studied lesions from 59 patients (21 B-cell lymphomas: 16 diffuse and five follicular; 11 cutaneous T-cell lymphomas, including seven MF; one T-immunoblastic lymphoma; 10 diffuse anaplastic large-cell lymphomas: two B, four T, and four of indeterminate phenotype; three Hodgkin's lymphomas; eight atypical lymphoid proliferations; four other lymphoid lesions, and one squamous-cell carcinoma) using primers to the gag, pol and pX regions of HTLV-I in the polymerase chain reaction (PCR) to detect relevant sequences. A total of 10 patients showed one or more PCR-amplifiable products, including five of 11 patients with cutaneous T-cell lymphomas (45%) as compared with one of 21 patients with B-cell lymphomas (4.3%). We did not find a high incidence of positivity in anaplastic large-cell lymphomas, as reported previously. Detectable HTLV-I sequences were not limited to any subtype of lymphoma, and a pX sequence was detected in a squamous-cell carcinoma. Sequence analysis of one amplified product from each of the three regions studied showed a 94.2, 100, and 98.9% homology to the corresponding prototypical gag, pol, and pX HTLV-I sequences, respectively, indicating that the amplified sequences were derived from HTLV-I or a very closely related virus. HTLV-I sequences were detected in a significant proportion of patients with cutaneous T-cell lymphoma, but their role in the pathogenesis of the neoplasm is still unclear.

Base Sequence↗

Cytoreductive therapy of multidrug-resistant hepatocellular carcinoma: negative regulation of growth using combination differentiation therapy.

In vitro studies of the mouse erythroleukemia cell system have identified at least 300 agents capable of inducing differentiation by mechanisms that remain to be elucidated. We have recently begun to examine recombinant cytokines as possible agents in inducing differentiation of tumor cells, specifically, malignant cells resistant to cytotoxic drugs. One such cytokine, transforming growth factor-beta (TGF-B1), is a multifunctional peptide that exists in at least five different isoforms in vertebrate species. Recently, there has been a great deal of interest in the role of TGF-B1 as an important multifunctional growth regulator that induces cells of mesenchymal origin to divide while inhibiting the growth of nontransformed epithelial cells. In this study, we combined the effects of the differentiation agent hexamethylene bisacetamide and the inhibiting effects of TGF-B1 on a multidrug-resistant human liver hepatocellular carcinoma and demonstrated the synergistic interaction of these two agents; this synergy resulted in a cell death rate of 80%. These data support the concept of programmed cell death and suggest that drug-resistant tumor cells may be susceptible to the combination of cytokines and differentiating agents.

Acetamides↗

In-patient withdrawal from long-term benzodiazepine use.

Twenty-one patients completed an intensive in-patient and out-patient group-based programme, to achieve withdrawal from long-term benzodiazepine dependence. By 6-month follow-up (post-withdrawal), eight patients (38%) had achieved a 'good' outcome. Generally, patients demonstrated moderate levels of psychiatric morbidity and depression in the pre-withdrawal phase; a diagnosis of a depressive disorder being associated with either an 'intermediate' or 'poor' outcome in comparison to patients receiving a diagnosis of anxiety disorder, who showed a predominantly 'good' outcome. Two patients committed suicide some time after withdrawal. Additionally, older patients fared less well than their younger counterparts. We conclude that maintenance benzodiazepine prescription, rather than withdrawal, may be the preferred treatment for some dependent patients. Furthermore, more data are required regarding the association, and causality, between depression and benzodiazepine withdrawal in long-term users.

Adult↗

Specific inhibitor of complement (C5)-derived chemotactic activity in systemic lupus erythematosus related antigenically to the Bb fragment of human factor B.

Serum and plasma from patients with active systemic lupus erythematosus contain a specific inhibitor of complement (C5)-derived chemotactic activity. We found that the inhibitor is antigenically related to the Bb fragment of complement factor B. Lupus plasma and purified inhibitor significantly reduced the chemotactic activity of zymosan-treated normal serum, an effect that was abolished by antibodies to factor B. Similar results were obtained when purified Bb was used. Neither purified inhibitor nor Bb inhibited the chemotactic activity of purified human C5a or C5a des Arg. As reported previously, the chemotactic activity of C5a des Arg was enhanced significantly by the addition of an anionic polypeptide (cochemotaxin) present in normal serum and plasma. Interestingly, both purified lupus inhibitor and Bb inhibited the chemotactic activity exhibited by mixtures of C5a des Arg and its cochemotaxin. This effect was due, most likely, to their ability to neutralize the enhancing effect of the cochemotaxin on the chemotactic activity of C5a des Arg. Immunoelectrophoresis and western blots revealed that the purified inhibitor reacted with anti-factor B and exhibited a similar charge and molecular weight as purified Bb.

Chemotactic Factors↗

Correspondence between the development of hemopoietic tissue and the time of colony formation by colony-forming cells.

The development of a haemopoietic tissue and the time when colony-forming cells in it formed detectable colonies were studied with in vivo spleen colony-forming units (CFUs) and in vitro high-proliferation-potential colony-forming cells (HPP CFC). Cells that form colonies first are developmentally more mature than those doing so later. Marrow containing mature spleen colony-forming cells formed fewer cells in the femora of recipients than that which contained early colony-forming cells. The growth curve of developmentally early high-proliferation potential-colony-forming cells was steeper than that of later cells. The time period before colony-formation occurs is a property of the colony-forming cell and is not due to regulatory mechanisms in the animal or to regulatory cells in the haemopoietic stroma.

Animals↗

A derivative of wheat germ agglutinin specifically inhibits formyl-peptide-induced polymorphonuclear leukocyte chemotaxis by blocking re-expression (or recycling) of receptors.

We examined the mechanism of action of a derivative of wheat germ agglutinin (WGA-D) which specifically and irreversibly inhibits N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced polymorphonuclear leukocyte (PMN) chemotaxis. At a concentration that completely inhibited PMN chemotaxis, WGA-D had no effect on either the uptake or release of [3H]-FMLP by PMN. Similarly, WGA-D did not affect either the short-term binding to, or internalization by, PMN of a fluoresceinated FMLP analog. WGA-D did interfere, however, with the re-expression (or recycling) of FMLP receptors by PMN that had been preincubated with 1 microM FMLP for 10 min at 4 degrees C. This effect was specific for WGA-D, because it was not observed when concanavalin A was used. Scatchard plot analysis of FMLP binding to PMN after receptor re-expression demonstrated that WGA-D-treated PMN had a significant diminution in the number of high affinity receptors. WGA-D-mediated inhibition of FMLP receptor re-expression was associated with inhibition of FMLP-induced PMN chemotaxis, but had no effect on either FMLP-induced PMN superoxide anion generation or degranulation. Studies using [125I]-WGA-D demonstrated that PMN did not internalize WGA-D spontaneously. PMN did internalize [125I]-WGA-D, however, when stimulated with FMLP. Internalization of WGA-D by FMLP-stimulated PMN was rapid, dependent on the concentration of FMLP, and specific. Internalization of [125I]-WGA-D by PMN did not occur when highly purified human C5a, instead of FMLP, was used as a stimulus. Subcellular fractionation studies demonstrated that [125I]-WGA-D and [3H]-FMLP were co-internalized by PMN, and segregated to a compartment co-migrating with Golgi markers. Western blot analysis, using PMN plasma membranes, demonstrated that WGA-D bound to a single membrane glycoprotein that migrated with an apparent m.w. of 62,000. The data indicate that WGA-D, perhaps by binding to the FMLP receptor, inhibits FMLP-induced PMN chemotaxis by blocking the re-expression (or recycling) of a population of receptors required for continuous migration.

Adult↗