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Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 37 records · Page 2Linked to original sources

A gene expression signature for recent onset rheumatoid arthritis in peripheral blood mononuclear cells.

BACKGROUND: In previous studies the presence of a distinct gene expression pattern has been shown in peripheral blood cells from patients with autoimmune disease. OBJECTIVE: To determine whether other specific signatures might be used to identify subsets of these autoimmune diseases and whether gene expression patterns in early disease might identify pathogenetic factors. METHODS: Peripheral blood mononuclear cells were acquired from patients with rheumatoid arthritis (RA) and analysed by microarrays containing over 4300 named human genes. Patients with RA for <2 years were compared with subjects with longstanding RA (average duration 10 years) and with patients with other immune or autoimmune diagnoses. RESULTS: Cluster analyses permitted separation of the patients with early RA (ERA) from those with longstanding disease. Comparison with other patient groups suggested that the ERA signature showed some overlap with that seen in the normal immune response to viral antigen as well as with a subset of patients with systemic lupus erythematosus. CONCLUSIONS: The ERA signature may reflect, in part, a response to an unknown infectious agent. Furthermore, shared features with some lupus patients suggest that common aetiological factors and pathogenetic pathways may be involved in these two autoimmune disorders.

Acute Disease↗

High-power, low-noise, Yb-doped, cladding-pumped, three-level fiber sources at 980 nm.

We present results on a high-power, cladding-pumped, Yb-doped fiber emitting at 977 nm in laser and ampllified-spontaneous-emission source configurations. We obtained up to 1.4 W of fiber-coupled, single-mode output power and slope efficiency as high as 68%. To our knowledge these are the highest powers efficiencies achieved from a single-mode fiber laser at approximately 980 nm and the first demonstrated results on a high-power amplified-spontaneous-emission source in this wavelength range. High power and high slope efficiency are achieved by using a high numerical aperture (> 0.7), a jacketed air-clad fiber, and a high-brightness pump source. Both types of sources exhibit relative intensity noise below -130 dB/Hz and are thus suitable for a wide range of applications.

Journal Article↗

Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma.

PURPOSE: The primary objective was to assess the duration of grade 4 neutropenia (neutrophil count < 0.5 x 10(9)/L) after one cycle of chemotherapy with etoposide, methylprednisolone, cisplatin, and cytarabine in patients randomly assigned to receive one dose of pegfilgrastim or daily filgrastim after chemotherapy. Febrile neutropenia, neutrophil profiles, time to neutrophil recovery, pharmacokinetics, and safety were also assessed. PATIENTS AND METHODS: An open-label, randomized, phase II study was designed to compare the effects of a single subcutaneous injection of pegfilgrastim (sustained-duration filgrastim) 100 micro g/kg per chemotherapy cycle (n = 33) with daily subcutaneous injections of filgrastim 5 micro g/kg (n = 33) in patients receiving salvage chemotherapy for relapsed or refractory Hodgkin's or non-Hodgkin's lymphoma. RESULTS: The incidence of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 69% and 68%, respectively. In addition, the mean duration of grade 4 neutropenia was similar in both groups (2.8 and 2.4 days, respectively). The results for the two groups were also not significantly different for febrile neutropenia, neutrophil profile, time to neutrophil recovery, or toxicity profile. A single subcutaneous injection of pegfilgrastim 100 micro g/kg produced a sustained serum concentration relative to daily subcutaneous injections of filgrastim. Filgrastim-treated patients received a median of 11 injections per cycle. CONCLUSION: Pegfilgrastim was safe and well tolerated in this patient population. A single injection of pegfilgrastim per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by daily injections of filgrastim. Once-per-cycle administration of pegfilgrastim simplifies the management of neutropenia and may have important clinical benefits for patients and healthcare providers.

Adult↗

Abnormal IL-2 receptor levels in non-pregnant women with a history of recurrent miscarriage.

BACKGROUND: Immunological abnormalities have been found in pregnant women with a history of recurrent miscarriage. This study compared interleukin-2 receptor (IL-2R) levels in non-pregnant women with a history of recurrent miscarriage with those found in serum from a non-pregnant group with no such history. METHODS: Group 1 comprised 49 non-pregnant women with a history of recurrent miscarriage (at least three consecutive miscarriages). Group 2 comprised 22 non-pregnant women with no history of miscarriage. Serum IL-2R levels were measured in all patients. RESULTS: The results obtained showed that although all women were not pregnant at the time of sampling, IL-2R levels were significantly higher in women in Group 1 compared with those in Group 2 (1589 +/- 1289 versus 1082 +/- 823 pg/ml; P < 0.05). Follow-up data were available for 21 women from Group 1. The next pregnancy ended successfully for 14 of these women, while seven miscarried again. The IL-2R levels obtained pre-pregnancy were not significantly different between the two groups (1480 +/- 910 versus 1356 +/- 716 pg/ml). CONCLUSION: This study has shown that non-pregnant women with a history of recurrent miscarriage have raised IL-2R levels. These increased pre-pregnancy IL-2R levels did not necessarily predict miscarriage for the next pregnancy.

Abortion, Habitual↗

Playing their part: the role of physical activity and sport in sustaining the health and well being of small rural communities.

It is widely recognised that the health of rural Australians is poor in comparison with their urban counterparts. Similarly, the role played by physical activity in maintaining health has been well researched and is well documented. However, little appears to have been published in recent years about the links between physical activity and health in rural communities. The objective of this article was to begin to address that gap. To achieve this, the article drew on research conducted in two small rural communities in Victoria Australia, and highlighted the role that physical activity and sport played in sustaining the health and wellbeing of individuals and communities in rural areas. Taking the World Health Organisation's definition of health (a state of complete physical, mental and social well-being and not merely the absence of disease) as its measure, the paper highlighted the many ways in which physical activity and sport in rural communities contribute to physical health, mental wellbeing and social cohesiveness. Based this finding, the authors suggest that physical activity and sport make a significant contribution to the health and wellbeing of rural people and their communities and suggest that further research is necessary to better define this apparent contribution.

Journal Article↗

The importance of the short-term leaching dynamics of wood preservatives.

The potential environmental impacts from the use of treated timber in aquatic areas is under scrutiny as a result of environmental legislation and reports of the deleterious environmental effects around treated structures. In this study leaching experiments of up to 3 weeks duration were conducted on two species of chromated copper arsenate treated timber, dried for different periods of time. Increased drying time significantly reduced leaching of Cr and As. The addition of a synthetic humic acid increased leaching of Cu and As, but reduced leaching of Cr. Putative risk assessments conducted using short-term copper leaching data suggested protocol design may influence decisions made regarding the environmental acceptability of such preservatives.

Arsenates↗

Hand-held three-dimensional dental X-ray system: technical description and preliminary results.

OBJECTIVE: To design, fabricate, and perform preliminary in vitro testing of a portable, hand-held, three-dimensional (3D) dental X-ray system using options unique to Tuned-Aperture Computed Tomography (TACT). The design allows for task-specific positioning over an unlimited range of user-selected angles and incorporates an integrated laser guidance system to constrain the focal-object distance. METHODS: A prototype system was fabricated consisting of an extremely lightweight X-ray source cantilevered from an aluminum gunstock-type handle to which a transparent radiation scatter shield was attached. Aiming was facilitated by task-specific visual cues used in conjunction with a spherically shaped radiolucent alignment jig coupled to the tissues of interest. Proper range was assured by a laser-assisted guidance system. The image transducer was an extrinsically modified commercially available CMOS device. The irradiated patient was simulated by a DXTTR phantom. RESULTS: The prototype demonstrated automated display of radiographed intra-oral tissues in three dimensions from arbitrary projection geometries and simulated task-specific sequences. Uncontrolled movements between exposures produced no obvious degeneration of 3D image quality. The aiming system minimized technical errors from misangulation. All dental regions in the phantom were imaged without difficulty. Projected risk was observed to be within clinically acceptable limits. CONCLUSIONS: Task-specific 3D images can be generated from as few as three uncontrolled projections. Total exposures can be prorated to levels not greatly exceeding those required for conventional two-dimensional radiographs of comparable image quality. Predicted radiation risks lie well below existing guidelines for occupational exposure.

Dental Equipment↗

A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis.

OBJECTIVE: To evaluate transvaginal and transabdominal ultrasound scanning, with or without Doppler, as a diagnostic test for the accurate diagnosis of pelvic endometriosis. METHODS: The MEDLINE (1966-2001) and EMBASE (1980-2001) databases were searched for relevant studies, published in English. Only studies fulfilling predefined criteria were selected. An assessment of quality was made for each study, and data were then reanalyzed using likelihood ratios to determine the usefulness of the test. RESULTS: In total, 67 papers were identified using the search strategy, of which 17 described relevant studies. Of these, seven fulfilled the inclusion criteria. All seven related to the use of transvaginal gray-scale imaging in the diagnosis of ovarian endometriomata specifically, rather than endometriosis. The positive likelihood ratios ranged from 7.6 to 29.8, and the negative likelihood ratios ranged from 0.1 to 0.4. Confidence intervals were wide. One paper addressed the use of conventional color Doppler with ultrasound: the positive likelihood ratio was 1.2, with a negative likelihood ratio of 0.4. One paper assessed the use of color Doppler energy imaging, and showed a positive likelihood ratio of 33.5 and a negative likelihood ratio of 0.1. CONCLUSIONS: Transvaginal ultrasound appears to be a useful test both to make and to exclude the diagnosis of an ovarian endometrioma.

Endometriosis↗

The prevalence and characteristics of physical and sensory disabilities in Northern Ethiopia.

PURPOSE: To identify disabilities and to determine their prevalence, age of onset and perceived cause in one urban and three rural areas in Northern Ethiopia. METHOD: A community based cross-sectional study of households that were selected by systematic sampling. Trained enumerators identified individuals with physical disabilities or epilepsy who were 5 years of age or older. RESULTS: The overall prevalence of disability in 4214 individuals was 4.9%. The more common forms were walking difficulty (1.7%), loss of vision in one or both eyes (1.5%), hand dysfunction (0.8%) and epilepsy (0.7%). Information provided by the interviewees revealed a pattern of early onset, with injury and infection prominent as perceived causes. The importance of injury and infections was confirmed by the findings in half the people with disability, who were examined by a surgeon. CONCLUSIONS: Disability is a major public health problem and more facilities for rehabilitation and social support are needed. Measures that are needed to reduce the prevalence include health promotion, preventing injury, widening immunization coverage, better childhood nutrition and effective treatment for infection and injury. Further research should include younger children, cover a wider range of disability and use more sensitive means to detect hearing loss.

Adolescent↗

Mutagenic and chemical modification of the ABA-1 allergen of the nematode Ascaris: consequences for structure and lipid binding properties.

The polyprotein allergens/antigens of nematodes (NPAs) are the only lipid binding proteins known to be produced as polyproteins. Cleavage of the large polyprotein precursors at regularly spaced proteinase cleavage sites produces 10 or 11 individual protein units of approximately 15 kDa. The sequences of these units are highly diverse within and between species, but there are five absolutely or strongly conserved amino acid positions (Trp15, Gln20, Leu42, Cys64, and Cys120). We have tested the role of these signature amino acids by mutational or chemical alteration of the ABA-1 protein of Ascaris, and examined the resulting modified proteins for perturbations of their lipid binding activities and structural integrity. Substitution of Trp15 and Gln20 both affect the stability of the protein in terms of resistance to thermal or chemical denaturation, but the ligand binding function is unaffected. Mutation of Leu42, however, disrupts both the protein's structural stability and functional integrity, as does chemical disruption of the disulfide bridge formed between Cys64 and Cys120. We also find that the C-terminal, but not the N-terminal, half of the protein binds fatty acids, indicating that the binding site may be confined to this part of the protein. This also supports the idea that the NPA units are themselves derived from an ancient duplication event, and that they may comprise two functionally distinct domains.

Allergens↗

Tantalus, a novel ASX-interacting protein with tissue-specific functions.

The Drosophila trithorax- and Polycomb-group (trxG and PcG) proteins maintain activated and repressed transcriptional states at specific target gene loci. The Additional sex combs (Asx) gene is of particular interest as it appears to function in both protein complexes and yet its effects on target genes are more restricted. A novel protein, Tantalus (TAN), was identified in a yeast two-hybrid screen for ASX-interacting proteins that might confer tissue-specific ASX functions. TAN contains consensus nuclear localization sites and binds DNA in vitro. However, its subcellular localization varies in a tissue-specific fashion. In salivary glands, TAN is predominantly nuclear and associates with 66 euchromatic sites on polytene chromosomes, more than half of which overlap with ASX. These loci do not include the homeotic genes of the ANT and BX complexes bound by other PcG and trxG proteins. Rather, tan mutant defects are restricted to sensory organs. We show that one of these defects, shared by Asx, is genetically enhanced by Asx. Taken together, the data suggest that TAN is a tissue-specific cofactor for ASX, and that its activity may be partially controlled by subcellular trafficking.

Amino Acid Sequence↗

Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study.

CONTEXT: The impact of depression on morbidity and mortality among women with human immunodeficiency virus (HIV) has not been examined despite the fact that women with HIV have substantially higher rates of depression than their male counterparts. OBJECTIVE: To determine the association of depressive symptoms with HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV. DESIGN: The HIV Epidemiologic Research Study, a prospective, longitudinal cohort study conducted from April 1993 through January 1995, with follow-up through March 2000. SETTING: Four academic medical centers in Baltimore, Md; Bronx, NY; Providence, RI; and Detroit, Mich. PARTICIPANTS: A total of 765 HIV-seropositive women aged 16 to 55 years. MAIN OUTCOME MEASURES: HIV-related mortality and CD4 cell count slope decline over a maximum of 7 years, compared among women with limited or no depressive symptoms, intermittent depressive symptoms, or chronic depressive symptoms, as measured using the self-report Center for Epidemiologic Studies Depression Scale. RESULTS: In multivariate analyses controlling for clinical, treatment, and other factors, women with chronic depressive symptoms were 2 times more likely to die than women with limited or no depressive symptoms (relative risk [RR], 2.0; 95% confidence interval [CI], 1.0-3.8). Among women with CD4 cell counts of less than 200 x 10(6)/L, HIV-related mortality rates were 54% for those with chronic depressive symptoms (RR, 4.3; 95% CI, 1.6-11.6) and 48% for those with intermittent depressive symptoms (RR, 3.5; 95% CI, 1.1-10.5) compared with 21% for those with limited or no depressive symptoms. Chronic depressive symptoms were also associated with significantly greater decline in CD4 cell counts after controlling for other variables in the model, especially among women with baseline CD4 cell counts of less than 500 x 10(6)/L and baseline viral load greater than 10 000 copies/microL. CONCLUSIONS: Our results indicate that depressive symptoms among women with HIV are associated with HIV disease progression, controlling for clinical, substance use, and sociodemographic characteristics. These results highlight the importance of adequate diagnosis and treatment of depression among women with HIV. Further research is needed to determine if treatment of depression can not only enhance the mental health of women with HIV but also impede disease progression and mortality.

Adolescent↗

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/m2/d [corrected]. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P =.016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

Acute Disease↗