Blood pressure and ageing: longitudinal cohort study.
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Aged↗
Biomedical subjects
S Cross
Publications and source records attributed to S Cross.
Allergy in general practice.
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Allergens↗
Distress symptoms among urban African American children and adolescents: a psychometric evaluation of the Checklist of Children's Distress Symptoms.
OBJECTIVES: To explore the factor structure of the Checklist of Children's Distress Symptoms (CCDS); to examine whether there is a higher-order single construct underlying the CCDS measure; and, to assess the association between children's distress symptoms, as reflected by the CCDS factors, and children's self-reported exposure to community violence (both victimization and witness events). DESIGNS: Community-based cross-sectional survey. SETTINGS: Ten public housing developments in an eastern metropolis. PARTICIPANTS: A total of 349 low-income urban African American children and adolescents (198 males; 151 females), 9 through 15 years of age. MEASURES: Children's distress symptoms, exposure to community violence, and selected demographic information including parental education, parental employment status, perceived health status, and school performance. ANALYSIS: Exploratory factor analysis was performed to determine the factorial structure of the CCDS measure. Second-order confirmatory factor analysis was performed to determine if there is a higher-order single underlying construct among CCDS factors. Pearson correlation coefficients were computed to assess the relationship between exposure to violence and CCDS factors. MAJOR FINDINGS: The exploratory factor analysis yielded a 6-factor solution for the CCDS measure with satisfactory internal consistency. The confirmatory factor model with a single second-order construct yielded a good fit to the data. In general, youth who experienced violent victimization or witnessed violent events reported higher levels of distress symptoms than those who did not. Distress symptoms labeled as "intrusive thoughts," "distraction," and "lack of belongingness" were most frequently associated with exposure to violence. Distress symptoms did not differ on the basis of sex or age. CONCLUSIONS: The CCDS has utility as a measure of distress symptoms among urban African American children and adolescents. Whereas analysis provided support for a single higher-order construct, using the proposed 6-factor structure should enhance our understanding of the psychological impact of exposure to violence on youth and contribute to more effective intervention efforts.
Adolescent↗
Gene silencing by methyl-CpG-binding proteins.
An important consequence of CpG methylation is the local silencing of gene expression. In part this can be mediated by direct interference of methylation with the binding of transcription factors. The major component of silencing, however, appears to be the binding of repressors that have an affinity for methyl-CpG. We have studied two proteins that bind to methylated DNA, methyl-CpG-binding protein 1 (MeCP1) and MeCP2. MeCP2 is a relatively abundant chromosomal protein whose localization in the nucleus is primarily dependent on CpG methylation. We find that MeCP2 is a potent transcriptional repressor with a genome-wide distribution. MeCP1 requires multiple methylated CpGs for binding and has previously been implicated as a methyl-CpG-dependent transcriptional repressor. Recent cloning of a candidate gene for a component of MeCP1 may provide clues to its mechanism of action.
Animals↗
Comparison between planar and tomographic radionuclide ventriculography for detecting inferior wall motion abnormalities.
Gated planar radionuclide ventriculography is routinely used for the detection of regional wall motion abnormalities of the left ventricle. However, for inferior wall motion abnormalities, sensitivity is known to be low in the left anterior oblique 'best septal' projection, although improved if a left posterior oblique (LPO) view is also acquired. Gated tomography of the cardiac blood pool is now available. This study compared the sensitivity of planar 'best septal' projection, LPO and tomographic radionuclide ventriculography in the detection of inferior wall motion abnormalities. Thirty-two patients consisting of 18 with previous inferior myocardial infarction and 14 normal controls were studied. All patients underwent equilibrium planar 'best septal', planar LPO and then tomographic radionuclide ventriculography. Inferior wall motion abnormality was detected in 'best septal' in eight (44%) patients, LPO in 12 (67%) and tomography in 17 (94%) patients, respectively. Tomographic radionuclide ventriculography was best at detecting inferior wall motion abnormality while planar LPO projection is better than 'best septal' projection.
Aged↗
Genetic determinants of morphine activity and thermal responses in 15 inbred mouse strains.
Mice from 15 standard inbred strains were tested for sensitivity to two effects of acute morphine administration, open-field activity, and body temperature changes, at doses of 0, 4, 8, 16, and 32 mg/kg, I.P. Large strain differences were consistently observed, indicating a substantial degree of genetic determination of these traits. For morphine-induced activity, some strains were markedly insensitive to all doses (e.g., C3H/He, CE), while others showed increases and some decreases at the same morphine dose. For thermal responses, one strain was insensitive to all doses employed (C3H/He), while others showed marked hypothermia and some hyperthermia at the same dose. Although strains differed in brain morphine concentrations at time of behavioral testing, pharmacokinetic differences were unrelated to both measures of morphine sensitivity. Correlations among strain means (estimates of genetic correlations) were rather high across doses within each measure, indicating that strain differences to a given effect of morphine were rather stable across doses. This suggests substantial commonality in genetically mediated mechanisms across the dose range used for activity, and also for thermal responses. In contrast, genetic correlations between activity and thermal responses were not significant at any dose, indicating that these two traits are largely genetically independent.
Analgesics, Opioid↗
Orbital emphysema in a collegiate basketball player.
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Adult↗
Identification of a cytotoxic T-lymphocyte response to the novel BARF0 protein of Epstein-Barr virus: a critical role for antigen expression.
The Epstein-Barr virus (EBV)-encoded BARF0 open reading frame gene products are consistently expressed in EBV-positive Burkitt's lymphoma (BL) cell lines, nasopharyngeal carcinoma cell lines, and lymphoblastoid cell lines (LCLs). Here we show that the BARF0 sequence includes an HLA A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope. By using theoretically predicted HLA A2 binding motifs and peptide-loaded antigen presentation-deficient T2 cells, polyclonal BARF0-specific CD8(+) CTLs were isolated from four different healthy EBV-seropositive donors but not from two seronegative donors. These CTL lines recognized the peptide epitope LLWAARPRL, which was found to be conserved in 33 of 34 virus strains originating from Caucasian, African, and Asian individuals. The BARF0-specific CTL lines could lyse EBV-negative BL cells stably transfected with the BARF0 gene but did not kill HLA A2-matched EBV-positive BL cells and LCLs in a standard 51Cr release assay. Reverse transcriptase PCR analysis demonstrated that these EBV-positive cell lines expressed significantly lower levels of BARF0 mRNA than transfected cells. This data indicated that the BARF0 epitope could be endogenously processed; however, antigen levels in the target cell were a limiting factor for the effective interaction between BARF0-expressing cells and CTLs. The limited expression of BARF0 antigen in EBV-infected BL cells and LCLs might contribute to the escape of immune recognition from virus-specific CTLs present in the host.
Amino Acid Sequence↗
Evidence that the expression and phosphorylation status of pleckstrin is modulated by Epstein-Barr virus in human B lymphocytes.
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B-Lymphocytes↗
Sequence and transcriptional analysis of groES and groEL genes from the thermophilic bacterium Clostridium thermocellum.
The groESL operon from Clostridium thermocellum (Ct) has been isolated and sequenced, revealing two ORFs of 285 and 1626 nt, separated by 48 nt. The first ORF encoded a 94-aa 10.6-kDa GroES homologue; the second encoded a 541-aa polypeptide of 57.6 kDa, that exhibited 61% and 77% sequence identity with GroEL from Escherichia coli (Ec) and Clostridium acetobutylicum (Ca), respectively. A putative tsp, preceded by -10 and -35 consensus promoters, was identified upstream of groES. This was followed by an inverted repeat observed previously in bacterial heat shock genes. A 15-nt palindrome characteristic of a Rho-independent transcription terminator, was located downstream of groEL. The first nt of the groES translational start codon was preceded (7 nt) by a putative RBS (AGGAGG); a second RBS sequence was located 8 nt upstream of the groEL start. Production of GroE homologues by Ct was constitutive, but was enhanced significantly during a temperature upshift from 60 degrees C to 70 degrees C. The Ct GroEL, expressed in Ec as a fusion protein with GST, was purified, free of contaminating Ec GroEL.
Blotting, Northern↗
A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy.
The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.
Autopsy↗
Blood pressure and cognitive decline in healthy old people.
Both hypertension and cognitive decline are common in old age. We sought to examine the effects of blood pressure (BP) on rates of cognitive decline in a longitudinal study of community-resident healthy old people. A total of 603 initially healthy old people aged over 69 years were visited at home. Subject's age, years of full-time education, Social Occupational Classification, health status and medication use were recorded. Sitting systolic and diastolic BP was measured, and the Mini-Mental State Examination (MMSE) and National Adult Reading Test (NART) administered. Follow-up was planned after 4 years: 69 subjects were dead, 15 were too unwell and 12 had moved away; 78 subjects either refused or failed to reply. Psychometric tests were administered to the remaining 429 (71.1%) after a median period of 4.20 years. Forty-two subjects had significant sensory impairment or interrupted testing. No significant differences in cognitive decline were found between those who had started medication (n = 163) and those remaining untreated (n = 224). Mean MMSE score change was 0.44 points (s.d. 2.07, P < 0.001). Entering all baseline variables into a stepwise regression analysis significant positive effects were found for initial MMSE score (beta = 0.50, P < 0.001), age (beta = 0.17, P < 0.001), systolic BP (beta = 0.16, P < 0.001) and period between testing (beta = 0.14, P = 0.004), and negative effect for NART-predicted IQ (beta = -0.16, P = 0.003).). We conclude that (1) older people exhibit faster age-associated cognitive decline as measured by MMSE; (2) people with higher NART-predicted IQs are relatively protected; (3) people with high systolic BPs are at greater risk of cognitive decline.
Aged↗
Age-associated cognitive decline in healthy old people.
BACKGROUND: disease often confounds the identification of risk factors for age-associated cognitive decline in elderly subjects. If the cognitive effects of ageing are to be distinguished from those of disease, healthy people need to be studied. METHODS: we examined the effects of incident disease and drug prescription on cognitive change in a sample of initially healthy old people in a longitudinal study and related these to age, education, social class and blood pressure. We screened general practice case notes of 10,000 patients aged 70 years and over resident in Edinburgh to identify potentially healthy subjects. We visited 1467 potential subjects at home and enquired directly about health problems and medications, administered the Mini-Mental State Examination (MMSE) and National Adult Reading Test and recorded educational attainment, occupation and blood pressure. RESULTS: 603 subjects (237 male, 366 female), mean age 75.7 years (range 70-88 years), reported no health problems and were taking no regular medications. Four years after the initial visit we determined the outcome of all 603 subjects and retested available survivors. Psychometric tests were then administered to the 429 (71.1%) available survivors after a median period of 4.2 years (69 subjects were dead, 15 were too unwell, 12 had moved away and 78 either refused or failed to reply). Forty-two subjects had significant sensory impairment or interrupted testing, 195 remained in good health, 29 reported or had documented disease but were on no regular medication and 163 were on regular medication for diseases diagnosed during the follow-up period. MMSE score declined by 0.3 points in the healthy group (P < 0.048). However, once a single outlier whose MMSE score fell from 29 to 22 was excluded, the mean decline for the remainder was non-significant at 0.2 points (P = 0.079). There was no significant difference in cognitive decline between those who had and those who had not started medication (P = 0.59). CONCLUSIONS: the study fails to support the hypothesis that cognitive decline can be attributed to age alone in healthy old people. If such a decline exists, we consider that it is unlikely to account for loss of more than 0.1 MMSE point per year.
Aged↗
Risk factors for developing multiple sclerosis after childhood optic neuritis.
We reviewed the records of all children (younger than 16 years of age) who presented with a diagnosis of optic neuritis (ON) identified through the comprehensive records-linkage system at the Mayo Clinic and identified 94 cases between 1950 and 1988 with a documented history of idiopathic ON. Detailed follow-up information was available on 79 patients, with a median length of follow-up of 19.4 years. Life-table analysis showed that 13% of the 79 patients with isolated ON had progressed to clinically or laboratory-supported definite multiple sclerosis (MS) by 10 years of follow-up, 19% by 20 years, 22% by 30 years, and 26% by 40 years. Gender, age, funduscopic findings, visual acuity, or family history of either ON or MS did not predict the development of MS. The presence of bilateral sequential or recurrent ON increased the risk of developing MS (p = 0.002; hazard ratio = 5.09), whereas the presence of infection within 2 weeks before the onset of ON decreased the risk of developing MS (p = 0.060; hazard ratio = 0.24). This study of childhood ON supports the lower risk of recurrence and progression to MS compared with adults.
Adolescent↗
Revised guidelines on asthma management.
The revised guidelines on asthma separate the management of children under five from that of adults and older children. A 'step' approach to treatment is advocated; with the recommendation that patients begin on the lowest level of medication that can control symptoms.
Adult↗
The management of acute asthma.
Health professionals likely to come into contact with people experiencing an acute episode of asthma, such as school nurses, ambulance personnel and A&E staff, need clear guidelines on management. The British Thoracic Society guidelines, revised this year, advise on the categorisation of asthma, assessment and treatment.
Acute Disease↗