Follicular lymphoma with trisomy 18 exhibiting loss of BCL-2 expression on transformation to a large cell lymphoma.
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Chromosomes, Human, Pair 18↗
Biomedical subjects
Margaret Jones
Publications and source records attributed to Margaret Jones.
The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas.
We previously developed a multivariate model based on the RNA expression of 6 genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistologic analysis of over 1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is expressed as a nuclear marker in normal germinal-center (GC) B cells and GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid and myeloid precursors and in megakaryocytes and also in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, natural killer (NK), and plasma cell neoplasms and was absent from nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.
Adaptor Proteins, Signal Transducing↗
Mental health screening in armed forces before the Iraq war and prevention of subsequent psychological morbidity: follow-up study.
OBJECTIVE: To assess whether screening for mental disorder before the start of the 2003 Iraq war would have predicted subsequent mental disorders. DESIGN: Longitudinal cohort study of the United Kingdom armed forces. PARTICIPANTS: 2820 of 2873 personnel of the three services who completed an initial questionnaire in 2002 were asked to complete a second questionnaire between June 2004 and 2 March 2006. SETTING: Regiments, air stations, bases, ships, and homes for those who had left the services. MAIN OUTCOME MEASURES: Positive and negative likelihood ratios, and positive and negative predictive value of first assessment compared with assessment two to three years later of post-traumatic stress disorder, general health questionnaire, physical symptoms, self perception of health, and alcohol misuse for the entire group and for those deployed to the Iraq war. RESULTS: The response rate to the follow-up questionnaire was 69%, adjusted for return to senders. The positive likelihood ratio of post-traumatic stress disorder was high (13.1, 95% confidence interval 7.2 to 23.8), but the negative likelihood ratio was close to 1 (0.78, 0.67 to 0.91). The positive predictive values were low because of the low prevalence of post-traumatic stress disorder in the period before the Iraq war. The positive likelihood ratios for the other psychological assessments varied between 2.7 and 5.6, and the negative likelihood ratios were slightly lower than for post-traumatic stress disorder, indicating that these were not good candidates for screening. Results were the same for the analyses restricted to those who were deployed. CONCLUSIONS: Screening for common mental disorders before deployment in this cohort would not have reduced subsequent morbidity or predicted post-traumatic stress disorder, but this may change if there is a considerable increase in the prevalence of the disorder.
Cohort Studies↗
Is there an Iraq war syndrome? Comparison of the health of UK service personnel after the Gulf and Iraq wars.
BACKGROUND: UK armed forces personnel who took part in the 1991 Gulf war experienced an increase in symptomatic ill health, colloquially known as Gulf war syndrome. Speculation about an Iraq war syndrome has already started. METHODS: We compared the health of male regular UK armed forces personnel deployed to Iraq during the 2003 war (n=3642) with that of their colleagues who were not deployed (n=4295), and compared these findings with those from our previous survey after the 1991 war. Data were obtained by questionnaire. FINDINGS: Graphs comparing frequencies of 50 non-specific symptoms in the past month in deployed and non-deployed groups did not show an increase in prevalence of symptoms equivalent to that observed after the Gulf war. For the Iraq war survey, odds ratios (ORs) for self-reported symptoms ranged from 0.8 to 1.3. Five symptoms were significantly increased, and two decreased, in deployed individuals, whereas prevalence greatly increased for all symptoms in the Gulf war study (ORs 1.9-3.9). Fatigue was not increased after the 2003 Iraq war (OR 1.08; 95% CI 0.98-1.19) but was greatly increased after the 1991 Gulf war (3.39; 3.00-3.83). Personnel deployed to the Gulf war were more likely (2.00, 1.70-2.35) than those not deployed to report their health as fair or poor; no such effect was found for the Iraq war (0.94, 0.82-1.09). INTERPRETATION: Increases in common symptoms in the 2003 Iraq war group were slight, and no pattern suggestive of a new syndrome was present. We consider several explanations for these differences.
Health Status↗
The health of UK military personnel who deployed to the 2003 Iraq war: a cohort study.
BACKGROUND: Concerns have been raised about the mental and physical health of UK military personnel who deployed to the 2003 war in Iraq and subsequent tours of duty in the country. METHODS: We compared health outcomes in a random sample of UK armed forces personnel who were deployed to the 2003 Iraq war with those in personnel who were not deployed. Participants completed a questionnaire covering the nature of the deployment and health outcomes, which included symptoms of post-traumatic stress disorder, common mental disorders, general wellbeing, alcohol consumption, physical symptoms, and fatigue. FINDINGS: The participation rate was 62.3% (n=4722) in the deployed sample, and 56.3% (n=5550) in the non-deployed sample. Differences in health outcomes between groups were slight. There was a modest increase in the number of individuals with multiple physical symptoms (odds ratio 1.33; 95% CI 1.15-1.54). No other differences between groups were noted. The effect of deployment was different for reservists compared with regulars. In regulars, only presence of multiple physical symptoms was weakly associated with deployment (1.32; 1.14-1.53), whereas for reservists deployment was associated with common mental disorders (2.47, 1.35-4.52) and fatigue (1.78; 1.09-2.91). There was no evidence that later deployments, which were associated with escalating insurgency and UK casualties, were associated with poorer mental health outcomes. INTERPRETATION: For regular personnel in the UK armed forces, deployment to the Iraq war has not, so far, been associated with significantly worse health outcomes, apart from a modest effect on multiple physical symptoms. There is evidence of a clinically and statistically significant effect on health in reservists.
Cohort Studies↗
The burden of psychological symptoms in UK Armed Forces.
OBJECTIVE: To assess the prevalence of psychological symptoms during periods of relatively low deployment activity and the factors associated with each psychological health outcome. METHODS: A survey of 4500 randomly selected UK service personnel was carried out in 2002. The questionnaire included the General Health Questionnaire (GHQ-12), the post-traumatic stress disorder checklist (PCL), 15 symptoms and an assessment of alcohol intake. RESULTS: A total of 20% were above cut-offs for GHQ-12, 15% for symptoms, 12% for alcohol intake and 2% for PCL. Gender, age, excessive drinking and smoking were independently associated with most outcomes of interest. Number of deployments was independently associated with multiple symptoms and excessive drinking. High post-traumatic stress disorder score was more frequent in the Army and in lower ranks. CONCLUSIONS: Psychological symptoms are highly prevalent in UK Armed Forces. Many risk factors are associated with measures of psychological ill-health.
Alcohol Drinking↗
UK armed forces responses to an informed consent policy for anthrax vaccination: a paradoxical effect?
BACKGROUND: In recognition of concerns that anthrax vaccination might be a trigger for "Gulf war syndrome", anthrax vaccinations were offered to UK armed forces in the 2003 Iraq conflict using explicit as opposed to implicit consent, as is the policy for all other vaccinations. This paper examines responses of personnel to this policy. METHODS: Qualitative analysis of free text responses to a question inviting comments on any concerns about the anthrax vaccination, asked in the context of a questionnaire assessing military health amongst 1000 members of the UK armed forces following the invasion of Iraq in 2003. RESULTS: Two hundred and two (20.2%) respondents made comments reflecting concerns about the vaccine's effectiveness and its safety. These appeared to be magnified by suspicions about the motives behind the informed consent policy for anthrax but not other vaccinations. CONCLUSION: While the informed consent policy for anthrax vaccinations was intended to decrease concern, it may inadvertently have had the opposite effect.
Anthrax Vaccines↗
ZAP-70 expression in normal pro/pre B cells, mature B cells, and in B-cell acute lymphoblastic leukemia.
PURPOSE: The ZAP-70 gene is normally expressed in T and natural killer cells, where it is required for the T-cell receptor (TCR) signaling. More recently, it has been described that ZAP-70 contributes to the B-cell development at early stages of B-cell differentiation in mice. The purpose was to investigate the presence of ZAP-70 in normal pro/pre B cells and mature B cells and in tumoral cells from B-acute lymphoblastic leukemias (B-ALL). EXPERIMENTAL DESIGN: ZAP-70 expression was ascertained by flow cytometry, immunofluorescence, Western blot, and quantitative reverse transcription-PCR. Analysis of ZAP-70 and other signaling proteins of the pre-TCR/TCR was done by Western blot. RESULTS: ZAP-70 was expressed in pro/pre B cells but not in normal mature B cells derived from bone marrow, peripheral blood, or tonsil. Among tumoral cells, ZAP-70 was expressed in 56% of B-ALLs with pro/pre B-cell phenotype and in 4 of 6 Burkitt/ALL lymphomas. In B-ALL cells, expression of CD38 protein correlated with ZAP-70 expression (P = 0.05). Mutational analysis of the ZAP-70 gene revealed the absence of mutations in cases lacking ZAP-70 expression. Moreover, other elements of the pre-TCR/TCR signaling pathway, like LAT and Lck, were also found in B-ALL cells. CONCLUSIONS: Among normal B-cell subsets, ZAP-70 was found expressed in normal pro/pre B cells but not in a significant proportion of normal B cells with mature phenotype. Moreover, the presence of ZAP-70 in B-ALLs probably reflects their cellular origin. The lack of ZAP-70 expression in normal mature B cells suggests that its expression in mature-derived neoplasms with different cellular origin, such as Burkitt's lymphoma and chronic lymphocytic leukemia, might be due to an aberrant phenomenon.
Adolescent↗
Is the increased reporting of symptomatic ill health in Gulf War veterans related to how one asks the question?
BACKGROUND: Following the 1991 Gulf War (GW) there was much controversy surrounding service-related health effects. Evidence from the Vietnam experience suggested that self-reported ill health following that conflict might be related to how service during the conflict is framed. The aim of this article is to determine if a GW health effect persisted when the same questions were asked in a "non-GW" context. METHOD: Prevalence of physical and psychological health problems were ascertained in a study assessing health screening from a random sample of UK Armed Forces. Record linkage between the screening survey and service history was conducted to obtain information on participation in the GW. RESULTS: Differences in health outcomes were found between the GW and the non-GW groups. This difference existed for symptomatic measures (OR=1.84, 95% CI, 1.17-2.91) rather than psychological or behavioral measures. No differences were found in psychological measures such as PTSD or behavioral measures such as alcohol consumption. Those deployed to the GW had a poorer self-perception of health (OR=1.47, 95% CI 1.02-2.11). CONCLUSIONS: Even in the absence of framing, a Gulf-related ill health effect was found.
Attitude to Health↗
P.r.n. medication use in a psychiatric high-dependency unit following the introduction of a nurse-led activity programme.
This paper describes the introduction of a daily activity programme with clients who require psychiatric intensive care in two locked high-dependency units (HDUs). To evaluate the programme, a crossover study between the two units was undertaken with a convenience sample of clients. Baseline data of pro re nata (p.r.n.) medication dispensed to patients were collected for a period of 2 weeks from both locked units before the introduction of the programme. The programme was conducted for a period of 1 month in alternate locked units. Both non-intervention and active programme data were collected throughout the 6-month period of the study. Findings from the study demonstrated that an activity-based nursing intervention was effective in reducing the number of p.r.n. medications dispensed in a HDU compared with control conditions. The effects were statistically significant in one of the units and absent in the other. This study shows that a purposeful activity programme for severely disturbed psychiatric clients in a HDU setting can be effective in reducing disturbed behaviour and therefore the need for p.r.n. medication.
Adolescent↗
The meaning of self-perception of health in the UK armed forces.
OBJECTIVES: We assessed the characteristics of self-perception of health (SPH) in relation to psychological distress and physical symptoms, and willingness of servicemen to see their Medical Officer (MO) by their SPH rating. DESIGN: We randomly selected 4,500 servicemen to receive either a full or an abridged screening questionnaire. MEASURES: The full questionnaire included 6 items from the short-form 36 and the question on SPH, the General Health Questionnaire-12, the post-traumatic stress disorder checklist and 15 symptoms. The abridged questionnaire included a subset of items from the full questionnaire. All 'screen-positive' and a random 'screen-negative' sample were invited to see an MO. RESULTS: 67.1% out of 4,500 servicemen completed the questionnaires. SPH was strongly associated with a summary short form-36 (SF-36) measure. There was a strong association between SPH and all assessment scales regardless of length of the questionnaires (p<.001). Even among those with very good or excellent SPH, high scores denoting psychological distress were prevalent (8.1%). Good SPH provided the largest variations in symptoms and scores. Servicemen with a poor/fair SPH were no more likely to accept a visit to the MO than the rest. CONCLUSIONS: SPH is an excellent question for surveillance because it is highly associated with psychological health but, at an individual level, it may convey different meanings depending on the person's individual interpretation of the term health. Symptomatic social avoidance may be high among servicemen who have a poor/fair SPH and methods, such as buddy support, may be helpful in decreasing isolation among those who may need professional support.
Adult↗
FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-embedded tissue.
Over the last decade, fluorescence in situ hybridization (FISH) has become a firmly established technique in the diagnosis and assessment of lymphoid malignancies. However, this technique is not wide-ly used in the routine diagnostic evaluation of paraffin-embedded biopsies, most likely because of a perception that it is technically more demanding. There are also uncertainties regarding diagnostic thresholds and the way in which results should be interpreted. In this Review, we describe practical strategies for using FISH analysis to detect lymphoma-associated chromosomal abnormalities in routine paraffin-embedded lymphoma biopsies. Furthermore, we provide proposals on how FISH results should be interpreted (including how to calculate cutoff levels for FISH probes), recorded, and reported. An online appendix (available at http://jmd.amjpathol.org) details various simple, yet robust procedures for paraffin FISH analysis; it also provides additional information on the production of FISH probes, evaluating and reporting FISH results, sources for reagents and equipment, and troubleshooting. We hope that these suggestions will make FISH technology for the study of lymphoma biopsies more accessible to routine diagnostic and research laboratories.
Chromosome Aberrations↗
The differential expression of LCK and BAFF-receptor and their role in apoptosis in human lymphomas.
BACKGROUND AND OBJECTIVES: We explored the expression of LCK and BAFF-R (B-cell activating factor receptor) both of which are known to play a role in signaling and apoptosis, in routine tissue biopsies. It was hypothesized that their expression patterns might yield information on apoptosis as it occurs in normal and reactive lymphoid cells, and also be of value for the detection of lymphoma subtypes. DESIGN AND METHODS: Both molecules were studied in paraffin-embedded tissue sections and cell lines by immunoperoxidase staining, and were also studied by western blotting. Human tonsillar B-cell subsets were analyzed by flow cytometry for LCK expression. RESULTS: LCK was detected for the first time in germinal centers and, at lower levels, in mantle zone B cells. The presence of LCK in B cells was confirmed by western blotting. Cross-linking surface IgM reduced LCK expression whereas cross-linking surface CD40 appeared to have the opposite effect. BAFF-R was present on mantle zone B cells but absent or weakly expressed in germinal center cells. Most lymphomas of germinal center origin (e.g. follicular lymphoma) and also many mantle cell lymphomas, chronic lymphocytic leukemia (CLL) and most T-cell neoplasms expressed LCK. In contrast, BAFF-R was expressed in a variety of B-cell lymphomas, but often absent in grade 3 follicular lymphomas and diffuse large B-cell lymphomas (DLBCL). Both LCK-positive and BAFF-R-positive DLBCL tended to be of germinal-center phenotype. INTERPRETATION AND CONCLUSIONS: The reciprocal expression pattern of LCK and BAFF-R in germinal center and mantle zone B cells may reflect their opposing roles in apoptosis. Their detection in lymphoma tissue biopsies may therefore be of clinical relevance in predicting response to treatment.
Apoptosis↗
The effect of low estrogen state on serotonin transporter function in mouse hippocampus: a behavioral and electrochemical study.
Defects in serotonergic transmission, including serotonin transporter (SERT) function, have been implicated in depression, anxiety disorders and some aspects of schizophrenia. The sex steroid hormone estrogen is known to modulate functional SERT activity, but whether it is up- or down-regulated is unclear. The aim of the present study was to examine the effect of a low estrogen state in mice on the behavioral effect of drugs acting through the SERT, serotonin uptake kinetics and SERT density in the hippocampus. We compared control mice, ovariectomized (OVX) C57BL/6J mice and aromatase knockout (ArKO) mice that are unable to produce estrogen. Fluoxetine treatment, but not fenfluramine treatment, significantly increased prepulse inhibition (PPI), a measure of sensorimotor gating, in C57BL/6J mice. The effect of fluoxetine was greater in OVX compared to sham-operated mice. In ArKO and J129 wild-type mice, fluoxetine increased PPI to the same extent while fenfluramine increased PPI more in ArKO mice compared to controls. Measurement of the time-course for diffusion and reuptake of exogenous serotonin in the CA3 region of the hippocampus showed that, in OVX mice, the fluoxetine-induced slowing of signal decay after application of serotonin was enhanced when compared to sham-operated controls. Similarly, in ArKO mice, the effect of fluoxetine was enhanced, suggesting that SERT function was greater than in J129 wild-type controls. Measurement of SERT density by [3H]-citalopram autoradiography, revealed an 18% decrease in hippocampus of OVX mice compared to intact controls. SERT density was also significantly reduced in nucleus accumbens (26%) but not in other regions, such as the raphe nuclei. Together, these results suggest that a low estrogen state increases SERT activity in the hippocampus despite an apparent reduction in SERT density. The behavioral consequences of these changes depend on the model of estrogen state used.
Analysis of Variance↗
Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG.
In generalized myasthenia gravis (MG) patients without detectable acetylcholine receptor (AChR) antibodies (SNMG), the thymus is often reported as "normally involuted." We analyzed thymic compartments in 67 patients with generalized MG, with AChR antibodies (AChR+, n = 23), with muscle-specific kinase (MuSK) antibodies (MuSK+, n = 14) or with neither (MuSK-, n = 30), and in 11 non-MG controls. Four of 14 MuSK+ thymi had rare small germinal centers, but overall they were not different from age-matched controls. However, approximately 75% MuSK- samples showed lymph node-type infiltrates similar to those in AChR+ patients, but with fewer germinal centers. These variations may explain some apparent differences in responses to thymectomy in SNMG.
Adolescent↗
Estrogen, a fundamental player in energy homeostasis.
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Animals↗
Unmet expectations in primary care and the agreement between doctor and patient: a questionnaire study.
BACKGROUND: Questionnaires completed respectively by doctor and patient may give conflicting views of what actions the doctor took during a consultation in primary care. This disagreement will affect an assessment of whether patient expectations of care were met, and may itself be influenced by fulfillment of expectations. OBJECTIVE: To investigate how patient expectations, and patient and doctor reports of doctor's actions in a primary care setting are associated. DESIGN: Questionnaire survey. SETTING: Fifty Royal Navy, Army and Royal Air Force medical centres. PARTICIPANTS: A total of 117 members of the British Armed Forces with a health problem identified by a screening questionnaire, and their medical officers. MAIN OUTCOME MEASURES: Patient and doctor reports following a consultation indicating whether the doctor gave a prescription, made a referral or did tests, and patient expectations of these outcomes. RESULTS: Agreement between patient and doctor (kappa) was 0.81 for prescribing, 0.69 for referral and 0.54 for tests. The prevalence of unmet expectations was higher when estimated from doctors' reports than from patients' reports (prescription P=0.016; referral P=0.065; tests P=0.092; difference of 6% in each case). Patient and doctor were more likely to disagree on what happened if the action reported by the doctor did not match the patient's expectations (all P<0.01, except for when doctor reported doing tests P=0.058). CONCLUSION: Whether or not a doctor's actions appear to fulfil patient expectations in a primary care consultation depends on whether those actions are reported by the doctor or the patient.
Adult↗
Antibody techniques used in the study of anaplastic lymphoma kinase-positive ALCL.
Antibodies enable relatively simple, rapid, and reproducible studies to be performed on protein expression in both normal and neoplastic cells. The availability of suitable reagents for routine diagnostic use has revolutionized the study of leukemia and lymphoma pathology. The use of antibodies specific for anaplastic lymphoma kinase (ALK) protein has permitted the identification of the tumor entity ALK-positive from the poorly defined morphological category of anaplastic large cell lymphoma. Antibody techniques have also provided major new insights into the biology of these tumors. This chapter describes the use of antibodies in both immunolabeling (immunocytochemical and immunofluorescence) procedures and in biochemical procedures in the study of ALK-positive ALCL.
Anaplastic Lymphoma Kinase↗