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At least 19 recordsLinked to original sources
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2001

Morality is not a curable disease: probing the history of venereal diseases, morality and prostitution. [Review of: Spongberg, M. Feminizing venereal disease: the body of the prostitute in nineteenth-century discourse, 1997; Fisher, T. Prostitution and the Victorians, 1997; Mooij, A. Out of otherness: characters and narrators in the Dutch venereal disease debates 1850-1990, 1998; Merians, LE. The secret malady: venereal disease in eighteenth century Britain and France, 1996; Brandt, A; Rozin P. Morality and health, 1997; Lewis, M. Thorns on the rose: the history of sexually transmitted diseases in Australia in international perspective, 1998; Lundberg, A. Care and coercion: medical knowledge, social policy and patients with venereal disease in Sweden, 1999].

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Historiography↗
PubMed2003

Prevalence of left main coronary artery disease, of three- or four-vessel coronary artery disease, and of obstructive coronary artery disease in patients with and without peripheral arterial disease undergoing coronary angiography for suspected coronary artery disease.

Data from the present investigation showed that the prevalence of current cigarette smoking, current or ex-cigarette smoking, systemic hypertension, diabetes mellitus, and dyslipidemia was significantly higher in patients with peripheral arterial disease (PAD) than in patients without PAD. The present report also showed that compared with patients without PAD undergoing coronary angiography for suspected coronary artery disease (CAD), patients with PAD undergoing coronary angiography for suspected CAD had a higher prevalence of left main CAD (18% vs <1%), a higher prevalence of 3- or 4-vessel CAD (63% vs 11%), and a higher prevalence of obstructive CAD (98% vs 81%).

Adult↗
PubMed2003

Association of abnormal serum lipids in elderly persons with atherosclerotic vascular disease and dementia, atherosclerotic vascular disease without dementia, dementia without atherosclerotic vascular disease, and no dementia or atherosclerotic vascular disease.

BACKGROUND: Observational data have shown that the use of statins was associated with a lower prevalence of vascular dementia and of Alzheimer's disease. METHODS: We investigated in an academic nursing home the association of dyslipidemia with atherosclerotic vascular disease (group 1), atherosclerotic vascular disease without dementia (group 2), dementia without atherosclerotic vascular disease (group 3), and no dementia or atherosclerotic vascular disease (group 4). RESULTS: Increased serum low-density lipoprotein (LDL) cholesterol was present in 36 of 50 group 1 patients (72%), in 34 of 50 group 2 patients (68%), in 34 of 50 group 3 patients (68%), and in 18 of 50 group 4 patients (36%) (p =.0003 for 1 versus 4; p = 0.001 for 2 versus 4 and 3 versus 4). Decreased serum high-density lipoprotein (HDL) cholesterol was present in 34 of 50 group 1 patients (68%), in 35 of 50 group 2 patients (70%), in 32 of 50 group 3 patients (64%), and in 16 of 50 group 4 patients (32%) (p =.0003 for 1 versus 4; p =.0001 for 2 versus 4; p =.001 for 3 versus 4). Hypertriglyceridemia was not significantly different in the 4 groups. CONCLUSIONS: The prevalence of increased serum LDL cholesterol and decreased serum HDL cholesterol were significantly higher in elderly patients with atherosclerotic vascular disease plus dementia, atherosclerotic vascular disease without dementia, and dementia without atherosclerotic vascular disease than in patients with no dementia or atherosclerotic vascular disease.

Age Distribution↗
PubMed1989

[123I-IMP-SPECT finding of a case of presenile dementia with motor neuron disease--comparison between Alzheimer's disease, Pick's disease and presenile dementia with motor neuron disease].

Cross-sectional X-CT and 123I-IMP-SPECT studies comparing patients with presenile dementia with motor neuron disease (52-year-old, female), with Alzheimer's disease (51-year-old, male) and Pick's disease (49-year-old, male), have found a pattern of reductions in regional cerebral blood flow; the most severe reductions have been in fronto-temporal regions in cases of Pick's disease and presenile dementia with motor neuron disease. 123I-IMP-SPECT in a patient with presenile dementia with motor neuron disease differed significantly from uptake in a case with Alzheimer's disease. Although these findings should be evaluated as part of a prospective longitudinal study with X-CT and 123I-IMP-SPECT, it could be suggested that the development of these diseases has different pathophysiologies.

Alzheimer Disease↗
PubMed1988

Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease.

Polyclonal antibodies were raised which have a high affinity for conjugated ubiquitin. Immunocytochemistry was performed on paraffin sections of tissues showing well-characterized inclusion bodies. Ubiquitin was found as a component of the intermediate filament inclusion bodies characteristic of several major diseases including Lewy bodies of Parkinson's disease, Pick bodies of Pick's disease, Mallory bodies of alcoholic liver disease, cytoplasmic bodies of a specific myopathy, and Rosenthal fibres within astrocytes. Ubiquitin was also present in the three histological lesions characteristic of Alzheimer's disease. These observations suggest a fundamental role for ubiquitin in the formation of intermediate filament inclusion bodies in man, and have implications regarding the pathogenesis of these important diseases.

Alzheimer Disease↗
PubMed2000

Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.

BACKGROUND: Heartburn affects 25% of the adult population on a monthly basis and represents the core symptom of gastro-oesophageal reflux disease (GORD). Treatment is readily available and puts a large demand on healthcare budgets. Research in the past has focused largely on the treatment of oesophagitis. A majority of GORD patients show no endoscopic abnormalities and in daily practice most patients are treated empirically. OBJECTIVES: Summarise, quantify and compare the efficacy of the short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in the empirical treatment of GORD and the treatment of endoscopy negative reflux disease (ENRD). SEARCH STRATEGY: Electronic searches were performed of the Cochrane Controlled Trials Register, MEDLINE and EMBASE. Bibliographies were screened. SELECTION CRITERIA: Included were randomised controlled trials focussing on symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be classifiable in the empirical treatment group (no endoscopy used in treatment allocation) or in the endoscopy negative reflux disease group (no endoscopic signs of erosive oesophagitis). DATA COLLECTION AND ANALYSIS: Data from included trials were extracted by two reviewers independently. The impact of interventions was expressed as relative risks (RR) together with 95% confidence intervals (95% CI). Meta-analysis was only performed if there were sufficient trials of similar comparisons reporting the same outcomes. Relative risks were combined for binary outcomes. MAIN RESULTS: Twenty-one trials were included: eleven in the empirical treatment group, seven in the ENRD group and three in both. In empirical treatment of GORD the RR for heartburn remission in placebo-controlled trials for PPI was 0.35 (1 trial, 95% CI 0.26 to 0.46), for H2RAs 0.77 (2 trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (1 trial, 95% CI 0.73 to 1.01). In direct comparison PPIs were significantly (p<0.05) more effective than H2RAs (3 trials, RR 0.67, 95% CI 0.57 to 0.80) and prokinetic's (2 trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, RR for heartburn remission for PPI versus placebo was 0.68 (4 trials, 95% CI 0.53 to 0.88) and for H2RA versus placebo was 0.84 (2 trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.69 (2 trials, 95% CI 0.39 to 1.20) and versus prokinetic 0.72 (1 trial, 95% CI 0.56 to 0.92). REVIEWER'S CONCLUSIONS: The findings in this review suggest that antisecretory drugs are effective in the empirical treatment of complaints likely to originate from GORD and in treatment of ENRD and furthermore that PPIs are superior to H2RAs in empirical treatment of typical GORD symptoms.

Endoscopy, Digestive System↗
PubMed1995

Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer's disease. II. Ageing, Korsakoff's disease, Parkinson's disease, and Alzheimer's disease.

Changes in the dendritic arborisation of Golgi-impregnated basal forebrain neurones with respect to size, shape, orientation, and topology of branching were quantitatively investigated in ageing, Alzheimer's disease (AD), Korsakoff's disease (KD), and Parkinson's disease (PD). A reorganisation of the whole dendritic tree characterized by an increase in both the total dendritic length and the degree of dendritic arborisation as well as by changes in the shape of the dendritic field was found during ageing, in KD, PD, and AD. Dendritic growth under these conditions was related to the extent of cell loss in basal forebrain nuclei. There appeared to be major differences, however, with respect to the overall pattern of dendritic reorganisation between AD on one side and ageing, KD, and PD on the other side. In both ageing and KD, dendritic growth was largely restricted to the terminal dendritic segments, resulting in an increase of the size of the dendritic field (pattern of "extensive growth") In AD, however, dendritic growth mainly resulted in an increase of the dendritic density within the dendritic field without being accompanied by an increase in the size of the volume occupied by the dendritic tree (pattern of "intensive growth"). In AD, aberrant growth processes were frequently observed in the perisomatic area or on distal dendritic segments of basal forebrain neurones of the reticular type. Neurones with aberrant growth profiles were typically located in the direct vicinity of deposits of beta/A4 amyloid. Perisomatic growth profiles were covered by the low-affinity receptor of nerve growth factor p75NGFR. Aberrant growth processes were not present in ageing, KD, and PD. On the basis of the present study, it is concluded that under certain degenerative conditions, reticular basal forebrain neurones undergo a compensatory reorganisation of their dendritic arborisation, a process that has become defective in AD, thereby converting a physiological signal into a cascade of events contributing to the pathology of the disease.

Adult↗
PubMed2002

Disease and diversity in history. (Reviews of: Cartwright, FF, Biddiss, M. Disease and history. Gloucestershire: Sutton Publishing Limited, 2000; Rotberg RI, ed. Health and disease in human history. Cambridge, MA: MIT Press, 2000; Cliff, A., Haggett, P., Smallman-Raynor, M. Deciphering global epidemics: analytical approaches to the disease records of world cities, 1888-1912. Cambridge: Cambridge University Press, 1998; Riley, JC. Rising life expectancy: a global history. Cambridge: Cambridge University Press, 2001; McMichael, T. Human frontiers, environments and disease: past patterns, uncertain futures. Cambridge: Cambridge University Press, 2001).

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Disease↗
PubMed2002

Hepatic manifestations of gastrointestinal diseases. Inflammatory bowel disease, celiac disease, and Whipple's disease.

The gastrointestinal tract and the liver are closely related anatomically, physiologically, and pathologically. Some disease associations are well documented, such as PSC in association with IBD, whereas others are less well defined. A heightened clinical suspicion is required in these patients who do not present with the classical disease associations. The underlying causes of their diseases are the subject of much debate and research, and their diagnosis and management remain challenging.

Animals↗
PubMed1996

Isolated polycystic liver disease as a distinct genetic disease, unlinked to polycystic kidney disease 1 and polycystic kidney disease 2.

Polycystic liver disease (PLD) is proven to occur either sporadically or in association with autosomal dominant polycystic kidney disease (ADPKD), whereas the existence of an isolated (i.e., without any kidney cyst) familial form is disputed. We describe a family with definitely isolated PLD transmitted through three generations and exclude the linkage of the disease to the genetic markers of PKD1 and PKD2, the two main loci responsible for ADPKD. These findings strongly support the existence of PLD as a genetic disease distinct from the known forms of ADPKD.

Cysts↗
PubMed2001

Cardioselective beta-blocker use in patients with reversible airway disease.

BACKGROUND: Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease. OBJECTIVES: To assess the effect of cardioselective beta-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component. SEARCH STRATEGY: A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to February, 2000. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language. SELECTION CRITERIA: Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta-agonist administration, or the presence of asthma as defined by the American Thoracic Society. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta-agonist given after the study drug. MAIN RESULTS: Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta-agonist response compared to placebo, a response not seen with beta-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]). REVIEWER'S CONCLUSIONS: Cardioselective beta-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be withheld from patients with mild-moderate reversible airway disease.

Acebutolol↗
PubMed2000

Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

BACKGROUND: Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. OBJECTIVES: To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality up to 28 days and before discharge, failure to extubate, mortality and / or chronic lung disease at 28 days and 36 weeks, CLD at 28 days and 36 weeks, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), pneumothorax, necrotizing enterocolitis (NEC), gastrointestinal bleeding, severe intraventricular hemorrhage (IVH), hypertrophic cardiomyopathy, late rescue with dexamethasone and abnormal neurological examination at follow-up were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, and NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There was only one small study of longterm follow-up and it did not show any increase in adverse neurological outcome. REVIEWER'S CONCLUSIONS: Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. No reliable evidence concerning long term effects is provided by the trials included in this review. In view of the evidence of an important increase in cerebral palsy and other adverse neurodevelopmental outcomes from trials in which postnatal steroid was begun either earlier or later than 7-14 days, there are reasonable grounds for extending this concern to moderately early initiation of steroid therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed.

Anti-Inflammatory Agents↗
PubMed2002

Biochemical analysis of tau proteins in argyrophilic grain disease, Alzheimer's disease, and Pick's disease : a comparative study.

Although argyrophilic grain disease is characterized histopathologically by tau-positive lesions known as argyrophilic grains located predominantly in limbic brain regions in the absence of other diagnostic neuropathologies, the biochemical correlates of argyrophilic grains in gray and white matter have not been reported. Thus, we analyzed insoluble (pathological) tau proteins in five argyrophilic grain disease brains in comparison with those seen in Alzheimer's disease and Pick's disease. Analyses of separately dissected gray and white matter samples from various cortical regions revealed that pathological tau in argyrophilic grain disease was confined primarily to mediotemporal neocortical gray and adjacent white matter, and also to the allocortex, amygdala, and hippocampus. The amounts of sarcosyl-insoluble tau in all five cases were substantially lower than in Alzheimer's disease and Pick's disease, but the amounts of sarcosyl-insoluble tau in white matter were higher or comparable to that detected in gray matter from the same region, which distinguishes argyrophilic grain disease from Alzheimer's disease. The banding patterns of tau isoforms in argyrophilic grain disease varied: in three cases they were similar to Alzheimer's disease, but in two other cases, 4 microtubule binding repeat (4R) tau predominated, which distinguishes argyrophilic grain disease from classical Pick's disease. The differences between these three diseases were re-enforced by the predominance of straight tau filaments from argyrophilic grain disease brains. Thus, we conclude that argyrophilic grain disease is a distinct tauopathy characterized by prominent accumulation of argyrophilic grains in limbic brain regions in association with the characteristic tau biochemical and ultrastructural profile reported here.

Aged↗
PubMed2000

Donepezil for mild and moderate Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the most common cause of dementia and is a primary degenerative disease of the brain of unknown cause. Onset is usually late in life with increasing impairment of memory, developing gradually into a global impairment of cognition, orientation, linguistic ability and judgement. The clinical course is accompanied by growing disability and dependency on care. One of the characteristic features of the disease is the widely variable rate of progression seen in different patients. Acetylcholine is an important neurotransmitter associated with memory, and abnormalities in cholinergic neurones (including cell loss) are among the many neurological and neurochemical abnormalities that develop in AD. One approach to lessening the impact of these abnormalities is to inhibit the breakdown of acetylcholine by blocking the relevant enzyme. Tacrine was the first compound approved as a treatment for AD in the US and worked in this way, but caused severe side effects. E2020 (donepezil, Aricept) is a second generation cholinesterase inhibitor and appears to be highly specific, with relatively few side effects. OBJECTIVES: The objective of this review is to assess whether or not donepezil improves the well-being of patients with mild or moderate Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials, was searched using the terms 'donepezil', 'E2020' and 'ARICEPT'. Medline, PsychLIT and EMBASE electronic databases were searched with the above terms. Members of the Donepezil Study Group and Eisai Inc were contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomised controlled trials in which treatment with donepezil was administered for more than a day and compared with placebo in patients with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (JSB & DB), pooled where appropriate and possible, and the weighted or standardised mean differences or Peto odds ratios (95%CI) estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: There are 4 included trials, covering treatment of 12 or 24 weeks duration in highly selected patients. The only information available on one trial (Gauthier 1998) is a conference abstract which reports no usable results. Available outcome data cover domains including cognitive function and global clinical state, but data on several important dimensions of outcome are not available. The results of three trials suggest a small beneficial effect of donepezil in improving cognitive function: at a 5mg/day dose, improvements measured -2.6 points (95%CI -3.5 -- -1.8) on weighted mean difference, in the midrange of the 70 point ADAS-Cog scale. The results of two trials show some improvement in global clinical state (assessed by an independent clinician) in those treated with donepezil compared to placebo. The patient's own rating of their Quality of Life showed no benefit of donepezil compared with placebo. There were significantly more withdrawals before the end of treatment from the 10mg/d (but not the 5mg/d) donepezil group compared with placebo, which may have resulted in some overestimation of beneficial changes at 10mg/d in progressively declining characteristics, as last available measures were used in analyses. A variety of adverse effects were recorded, but very few patients left a trial as a direct result of the intervention. REVIEWER'S CONCLUSIONS: In selected patients with mild or moderate Alzheimer's disease treated for periods of 12 or 24 weeks, donepezil produced modest improvements in cognitive function and study clinicians rated global clinical state more positively in treated patients. No improvements were present on patient self-assessed quality of life and data on many important outcomes are not available. The practical importance of these changes to patients and carers is unclear.

Alzheimer Disease↗