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Biomedical subjects

John Moore

Publications and source records attributed to John Moore.

At least 19 recordsLinked to original sources
PubMed2007

Profound thrombocytopenia related to G-CSF.

Severe thrombocytopenia in association with G-CSF therapy is extremely rare. Here we report a case of profound thrombocytopenia in a 57-year-old male with refractory cardiac ischemia, who received G-CSF during an angiogenesis trial. After 5 days of G-CSF therapy (10 microg/kg/day) the platelet count fell progressively to a nadir of 5x10(9)/L. The patient received steroid, immunoglobulin and platelet support and recovered without sequelae. Subsequent investigations suggested an underlying immune-mediated thrombocytopenia, which we hypothesize was exacerbated by G-CSF therapy.

Blood Cell Count↗
PubMed2006

A SYBR green-based real-time PCR method for detection of haemopoietic chimerism in allogeneic haemopoietic stem cell transplant recipients.

OBJECTIVE: To develop a reliable and rapid real-time quantitative polymerase chain reaction (Q-PCR) method using SYBR green to quantify chimerism in allogeneic haemopoietic stem cell transplant recipients. METHODS: Twelve specific nucleotide polymorphisms (NPs) were selected to identify informative markers for detecting chimerism in transplant donor/recipient pairs. One informative marker was then used in SYBR green Q-PCR to detect chimerism post-transplantation in each patient. The percentage of donor cells was calculated using a standard curve, constructed using artificially mixed donor/recipient chimeric DNA in 12 serial dilutions (0.01-100%). RESULTS: DNA from 37 donor/recipient pairs was screened for informative markers and 18 post-transplant samples were monitored for chimerism with SYBR green Q-PCR method. The Q-PCR was able to discriminate between recipient and donor genetic profiles in all 18 samples, and quantify the chimerism. These results were confirmed by at least one independent method, such as TaqMan Q-PCR, microsatellite and fluorescent in situ hybridisation (FISH) methods. The detection limit of this method was 0.1%, which was more sensitive than the two currently used microsatellite and FISH methods. CONCLUSION: The new single platform SYBR green Q-PCR method is capable of detecting all haemopoietic chimerism with high accuracy; hence, it may be used to replace the current detection methods.

Adult↗
PubMed2005

Early establishment of gamma-herpesvirus latency: implications for immune control.

The human gamma-herpesviruses, EBV and Kaposi's sarcoma-associated herpesvirus, infect >90% of the population worldwide, and latent infection is associated with numerous malignancies. Rational vaccination and therapeutic strategies require an understanding of virus-host interactions during the initial asymptomatic infection. Primary EBV infection is associated with virus replication at epithelial sites and entry into the circulating B lymphocyte pool. The virus exploits the life cycle of the B cell and latency is maintained long term in resting memory B cells. In this study, using a murine gamma-herpesvirus model, we demonstrate an early dominance of latent virus at the site of infection, with lung B cells harboring virus almost immediately after infection. These data reinforce the central role of the B cell not only in the later phase of infection, but early in the initial infection. Early inhibition of lytic replication does not impact the progression of the latent infection, and latency is established in lymphoid tissues following infection with a replication-deficient mutant virus. These data demonstrate that lytic viral replication is not a requirement for gamma-herpesvirus latency in vivo and suggest that viral latency can be disseminated by cellular proliferation. These observations emphasize that prophylactic vaccination strategies must target latent gamma-herpesvirus at the site of infection.

Animals↗
PubMed2005

Home visiting and child health surveillance attendance.

This project tested the hypothesis that low attendance rates at a Sure Start child health surveillance session might increase if appointments were preceded by intervention home visits from research assistants drawn from the local community. The assistants would explain the purpose of surveillance and discuss problems preventing attendance. A randomised control trial showed no increase in surveillance attendance after two-thirds of the intervention group were successfully visited. This negative finding was despite the partnership with local people acting as research assistants working well. Other factors that might have influenced attendance were investigated at an evaluation interview undertaken by community members in homes after the surveillance date. Only 55 per cent of the families could be contacted for evaluation. Six out of 10 of those who had no evaluation were the same families who had not attended the surveillance session. The reasons why these families missed surveillance sessions is yet to be identified. Further research is needed that explores the reason why some families do come for surveillance, the nature of the barriers to attendance in those who do not attend and to look for opportunities for fresh interventions that might give more children access to pre-school facilities.

Adult↗
PubMed2004

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia.

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3-4 months. Both cohorts produced naive T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort.

Alemtuzumab↗
PubMed2004

Adverse events associated with neonatal exchange transfusion in the 1990s.

OBJECTIVE: To determine the rates of adverse events associated with neonatal exchange transfusions performed for hyperbilirubinemia. STUDY DESIGN: Retrospective chart review of 55 neonates who underwent 66 exchange transfusions at two perinatal centers in Cleveland between 1992 and 2002. Demographic data, causes of jaundice, details of exchange method, and adverse events occurring within one week of exchange were recorded. At the time of exchange, 62% of infants had other neonatal morbidities. Outcomes were stratified according to gestational ages < or =32 weeks, 33 to 36 weeks, and > or =37 weeks. RESULTS: Overall, 74% of exchanges were associated with an adverse event. The most common events were thrombocytopenia (44%), hypocalcemia (29%), and metabolic acidosis (24%), of which 69%, 74%, and 44%, respectively, required treatment. There were two serious adverse events, both in infants with other serious neonatal morbidities: seizures in one infant and the death of a critically ill preterm infant (body weight 731 g, gestational age 25 weeks). There were no cases of sepsis, necrotizing enterocolitis, or cardiac arrest. Adverse events were more frequent in exchanges done on preterm infants: < or =32 weeks (87%), 33 to 36 weeks (78%), and > or =37 weeks (67%), and in infants with other neonatal morbidity (79% vs 57%; P=.08). Controlling for neonatal morbidity, we found the odds of an adverse event were significantly higher when both umbilical venous and arterial catheters were used compared with other methods of exchange (88% vs 58%; OR, 5.17; 95% CI, 1.1, 34.2; P=.03). CONCLUSIONS: The majority of adverse events associated with exchange transfusion are laboratory abnormalities and are asymptomatic and treatable.

Exchange Transfusion, Whole Blood↗
PubMed2004

NTP-CERHR expert panel report on the reproductive and developmental toxicity of methanol.

The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the Center is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction, including development, caused by agents to which humans may be exposed. Methanol was selected for evaluation by the CERHR based on high production volume, extent of human exposure, and published evidence of reproductive or developmental toxicity. Methanol is used in chemical syntheses and as an industrial solvent. It is a natural component of the human diet and is found in consumer products such as paints, antifreeze, cleaning solutions, and adhesives. It is used in race car fuels and there is potential for expanded use as an automobile fuel. This evaluation is the result of a 10-month effort by a 12-member panel of government and non-government scientists that culminated in a public Expert Panel meeting. This report has been reviewed by CERHR staff scientists, and by members of the Methanol Expert Panel. Copies have been provided to the CERHR Core Committee, which is made up of representatives of NTP-participating agencies. This report is a product of the Expert Panel and is intended to (1). interpret the strength of scientific evidence that a given exposure or exposure circumstance may pose a hazard to reproduction and the health and welfare of children; (2). provide objective and scientifically thorough assessments of the scientific evidence that adverse reproductive/development health effects are associated with exposure to specific chemicals or classes of chemicals, including descriptions of any uncertainties that would diminish confidence in assessment of risks; and (3). identify knowledge gaps to help establish research and testing priorities. The expert panel report becomes a central part of the subsequent NTP-CERHR Monograph. Each monograph includes the NTP Brief on the chemical under evaluation, the expert panel report, and all public comments on the expert panel report. The NTP Brief contains the NTP's conclusions on the potential for exposure to result in adverse effects on human development and reproduction. It is based on the expert panel report, public comments on the report, and relevant data published after the expert panel report was completed. NTP-CERHR Monographs are publicly available and are transmitted to appropriate health and regulatory agencies.

Adult↗
PubMed2004

Augmented reality laser projection device for surgery.

We have developed an augmented reality system capable of projecting preoperative plans directly onto a patient using rapidly scanned laser beams. Projected contours can typically represent cut paths, tumors or delineate boundaries of interest. The system can be used as part of, or a replacement for, conventional robotic Telesurgery systems. Because the graphics are projected, there is no degradation in surgeon's view due to optical components interposed between the surgeon's eye and the patient. This system has been designed to work with a common infrared 3D camera system used in image-guided surgery, and projects both visible and infrared beams. The IR beam enables surface digitization functions to be carried out using the camera. The clinical accuracy is in the range required by CAS procedures, around 1-2mm. The device will be particularly useful for executing precise preoperative plans and for teleconsultation applications, where planned or live consultations can be efficiently communicated to a less skilled local caregiver.

Canada↗
PubMed2003

Identification of circulating antigen-specific CD4+ T lymphocytes with a CCR5+, cytotoxic phenotype in an HIV-1 long-term nonprogressor and in CMV infection.

Antigen-specific CD4+ effector T cells primarily provide help for B-cell antibody responses and CD8+ cytotoxic T-lymphocyte (CTL) responses. We have found an expanded population of HIV-1 p24-specific, T-cell receptor V beta 17+, CD4+ T lymphocytes, defined by in vitro proliferative and interferon-gamma responses to a 15-mer Gag peptide, in the peripheral blood of an individual with long-term nonprogressive HIV-1 infection. Ex vivo, these cells were CCR5+ and CCR7-, consistent with an effector/memory function. Surprisingly, these cells highly expressed several proteins characteristic of cytotoxic lymphocytes, including TIA-1 (T-cell intracellular antigen 1; GMP-17/NKG7), granzymes A and B, CD161 (NKRP-1), and CD244 (C1.7/2B4). Following in vitro peptide stimulation, these cells produced interleukin 2 (IL-2) and intracellular CD40L, suggesting possible helper function, in addition to induction of perforin and cytotoxicity. A subset of cytomegalovirus (CMV)-specific CD4+ T cells in healthy adults similarly expressed these CTL markers and CCR5, ex vivo. Furthermore, this distinct subset of CD4+ T cells was significantly elevated in healthy CMV-seropositive adults, compared with CMV-seronegative individuals. These results suggest that CCR5+ CD4+ CTL may be a major effector mechanism of the immune response to viral infections in humans. Moreover, expression of CCR5 may render them particularly susceptible to cytopathic effects during progressive HIV-1 infection.

Adult↗
PubMed2003

X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch.

The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidinetryptophan switch that holds the receptor in its active conformation. Hydrogen bonding interactions with the ligand act to position the His-435 imidazole ring against the Trp-457 indole ring, allowing an electrostatic interaction that holds the AF2 helix in the active position. The neutral oxysterol 24(S),25-epoxycholesterol accepts a hydrogen bond from His-435 that positions the imidazole ring of the histidine above the pyrrole ring of the tryptophan. In contrast, the acidic T0901317 hydroxyl group makes a shorter hydrogen bond with His-435 that pulls the imidazole over the electron-rich benzene ring of the tryptophan, possibly strengthening the electrostatic interaction. Point mutagenesis of Trp-457 supports the observation that the ligand-histidine-tryptophan coupling is different between the two ligands. The lipophilic liver X receptor ligand-binding pocket is larger than the corresponding steroid hormone receptors, which allows T0901317 to adopt two distinct conformations. These results provide a molecular basis for liver X receptor activation by a wide range of endogenous neutral and acidic ligands.

Anticholesteremic Agents↗
PubMed2003

Differential gamma-herpesvirus distribution in distinct anatomical locations and cell subsets during persistent infection in mice.

Murine gamma-herpesvirus 68 (MHV-68) provides an important experimental model for analyzing gamma-herpesvirus latent infection. After intranasal infection with MHV-68, we analyzed the distribution of the virus in different anatomical locations and purified populations of cells. Our data show that long-term latency is maintained in a variety of anatomical locations and cell populations with different frequencies. Importantly, we demonstrate that although latency in the lung is established in a variety of cell subsets, long-term latency in the lung is only maintained in B cells. In contrast, splenic latency is maintained in macrophages and dendritic cells, as well as in B cells. In blood, isotype-switched B cells constitute the major viral reservoir. These results show that the cell subsets in which latency is established vary within different anatomical sites. Finally, we demonstrate that long-term latency is accompanied by a low level of infectious virus in lung and spleen. These data have important implications for understanding the establishment and maintenance of latency by gamma(2)-herpesviruses.

Animals↗
PubMed2003

Bilateral high-frequency synchronous discharges: a new form of tremor in humans.

OBJECTIVES: To report bilateral high-frequency synchronous discharges in a patient with a sporadic form of olivopontocerebellar atrophy; to investigate the electromyographic pattern, the coherence and cospectral density across limbs, and the resetting effects of electrical stimulation over the posterior fossa; and to highlight the clinical, electrophysiologic, and radiologic features of this new form of tremor associated with posterior fossa disorders. DESIGN: Case study of a patient clinically exhibiting a sporadic form of olivopontocerebellar atrophy associated with cerebellar and brainstem atrophy. SETTING: Research unit, university hospital. MAIN OUTCOME MEASURES: Electromyographic studies, coherence and cospectral density analysis, and calculation of a resetting index based on the timing of measured bursts and predicted bursts for an electrical stimulus given over the posterior fossa at increasing delays. RESULTS: Surface electromyographic recordings in forearm muscles revealed a low-frequency postural tremor in the upper limbs, with episodes of highly coherent tremor at a frequency of 14 Hz. Squared coherence and cospectral density was strong between agonist and antagonist muscles in the left and right upper limbs and across limbs for the high-frequency discharges. Electrical stimulation over the posterior fossa reset the explosive high-frequency bursts. The resetting index was 0.82 Hz. CONCLUSIONS: Our results show that bilateral high-frequency synchronous discharges may be associated with the sporadic form of olivopontocerebellar atrophy. Bilateral coherent bursting and resetting of this explosive postural tremor following electrical stimulation over the posterior fossa strongly suggest that the brainstem plays a key role in the network involved in the genesis of rhythmic bursts. We suggest that the high-frequency discharges are due to repetitive discharges in the reverberating cerebello-precerebellar circuits.

Aged↗
PubMed2003

The association between respiratory distress and nonpulmonary morbidity at 34 to 36 weeks' gestation.

OBJECTIVE: The study was undertaken to determine whether respiratory distress syndrome (RDS) is associated with an increased risk of nonpulmonary morbidity in neonates born between 34 to 36 weeks' gestation. STUDY DESIGN: We performed a matched case-control study of 75 infants with (cases) and 75 without (controls) RDS, delivered between 34 and 36 weeks' gestation. Infants with RDS and no other causes for respiratory failure (anomalies, hydrops, asphyxia) were included. Controls were matched for gestational age at birth, year of care, gender, plurality, and race. Inpatient records were reviewed for the incidence of nonpulmonary morbidities before discharge. McNemar test and conditional logistic regression were used to evaluate differences between cases and controls. RESULTS: Our study cohort was 69% male, 48% white, 33% African American, and 19% Hispanic. Cases had longer hospital (11 vs 7days) and neonatal intensive care unit stays (10 vs 7 days), and more frequent apnea-bradycardia (30% vs 5%), pneumonia (12% vs 1%), and suspected sepsis diagnoses (27% vs 3%), P <or=.008 for each. Antibiotic use (96% vs 45%), transfusion (20% vs 0%), phototherapy (57% vs 29%), and hyperalimentation (57% vs 4%) were more common in the RDS group, P <or=.002 for each. Other major morbidities (intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia) were uncommon in cases and controls. Similar results were obtained when controlling for mode of delivery and antenatal steroid use. CONCLUSION: RDS at 34 to 36 weeks is associated with increased morbidity and neonatal interventions. In the absence of RDS, major morbidity is uncommon.

Apnea↗
PubMed2003

Risk-awareness of cutaneous malignancies among rural populations.

The prevention of skin cancer relies not only on the knowledge of the risks of ultraviolet rays, but also on the appropriate measures to minimize solar exposure. We conducted a questionnaire-based survey among a rural population to evaluate perceptions regarding (i) sun-related behaviors, (ii) measures taken to protect themselves, and (iii) self-skin assessment knowledge. Questions included data on patients' knowledge of deleterious effects of sun exposure, their habits and perceptions about adequate protection, their knowledge of a suspicious cutaneous lesion, and if a physician had spoken to them about the risks of ultraviolet/solar exposure. One hundred and six adults (38 males and 68 females) seen in a primary care clinic were enrolled in our study. Of these, only 38.7% of our patients were concerned about their risk of cutaneous malignancies. On analysis of the sun-protection variables, we found an increased use of tanning beds among women and an increased use of hats in men. Interestingly, we also found that only 18% of respondents used sunscreen when anticipating sun exposure. With suspicious skin lesions, color of the lesion appeared to be the most concerning factor for the subjects, with increasing size being the second most likely factor of concern. Only 11.3% of respondents had a physician-performed skin assessment and only 19.8% performed self-skin assessments at least yearly. There seems to be a lack of appropriate knowledge regarding precancerous and cancerous skin lesions among rural communities. Increased patient education is urgently necessary in rural populations to decrease the growing incidence of cutaneous malignancies.

Adult↗