Trophoblast differentiation. An in vitro model for trophoblast giant cell development.
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Animals↗
Biomedical subjects
T J Peters
Publications and source records attributed to T J Peters.
Placental lactogen-I gene activation in differentiating trophoblast cells: extrinsic and intrinsic regulation involving mitogen-activated protein kinase signaling pathways.
Trophoblast giant cells are one of the primary endocrine cell types of the rodent placenta. Placental lactogen-I (PL-I) is the initial prolactin (PRL) family member expressed as trophoblast giant cells differentiate. In this report, we use the Rcho-1 trophoblast cell line as a model for studying the regulation of PL-I gene expression during trophoblast giant cell differentiation. Evidence is provided for trophoblast cell expression of epidermal growth factor receptor (EGFR), ErbB2, fibroblast growth factor receptor 1 (FGFR1), transforming growth factor-alpha, and heparin-binding EGF. EGF and FGF-2 stimulated PL-I mRNA and protein accumulation and PL-I promoter activity in a concentration-dependent manner. These latter growth factor actions on PL-I promoter activities were specifically inhibited by cotransfection with dominant negative constructs for EGFR and FGFRs respectively. Utilization of the mitogen-activated protein kinase (MAPK) pathway by EGF and FGF-2 in trophoblast cells was demonstrated by growth factor stimulation of a Gal4 DNA binding/Elk1 transactivational domain fusion construct, and more specifically by activation of extracellular signal regulated kinase and p38 MAPK. PL-I gene activation was also sensitive to disruption of MAPK and activation protein-1 (AP-1) signaling pathways. In conclusion, autocrine/paracrine pathways involving EGFR and FGFR1, MAPK and AP-1 are shown to participate in the regulation of the PL-I gene in differentiating trophoblast cells.
Analysis of Variance↗
Estimation of cardiovascular risk in hypertensive patients in primary care.
Assessment of absolute cardiovascular risk is a rational method of managing hypertension. General practitioners and practice nurses were asked to estimate absolute risk in a group of elderly hypertensive patients during clinical practice. Risk was correctly estimated in 21% of patients, underestimated in 63% of patients, and overestimated in 16% of patients. Unless primary health care professionals use cardiovascular risk charts or tables, treatment decisions in primary care may not be made against realistic estimates of patients' susceptibility to cardiovascular disease.
Aged↗
The first randomized controlled trial.
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Databases, Bibliographic↗
7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol in muscle as indices of oxidative stress: response to ethanol dosage in rats.
BACKGROUND: Alcohol-induced muscle disease (AIMD) encompasses both acute and chronic lesions, and affected patients exhibit concomitant functional and structural lesions. The pathogenic mechanisms are unknown, although it is possible that defects in the membrane-lipid domain are involved. Therefore, the effect of acute ethanol on membrane lipid from rat skeletal muscles (control, n = 7; ethanol, n = 7) was investigated. METHODS: Soleus and plantaris skeletal muscles were collected 24 hr after a single dose of 75 mmol/kg of ethanol. Lipids were analyzed by high-performance liquid chromatography with postcolumn chemiluminescence. RESULTS: We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in soleus muscles of control animals (1.29 nmol/g and 3.20 nmol/g, respectively) and in plantaris (1.83 and 5.18 nmol/g, respectively). These hydroperoxides were significantly elevated by acute ethanol, in not only plantaris but also soleus skeletal muscle of rats. In contrast, protein carbonyl concentration, another indicator of oxidative stress, albeit to proteins, was not significantly affected in either soleus or plantaris muscles of ethanol dosed rats. In addition, gas chromatographic study of fatty acid composition from phospholipid of rat muscle showed a significant increase of 18:2 by ethanol in plantaris as well as soleus. Concomitant decreases occurred in the nonessential/essential fatty acid ratios. CONCLUSIONS: This is the first report on 7alpha-OOH and 7beta-OOH accumulation in rat skeletal muscle, and it seems to reflect greater oxidative stress in the pathology of muscle of rats treated with acute ethanol. Together with the elevation of 18:2, these results signify perturbations in membrane lipids in response to ethanol, which may have important implications for the pathogenesis of alcohol-induced muscle disorders.
Animals↗
A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.
PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.
Humans↗
A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.
PURPOSE: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement. MATERIALS AND METHODS: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure. RESULTS: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure. CONCLUSIONS: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.
Aged↗
Scoring the short form ICSmaleSF questionnaire. International Continence Society.
PURPOSE: The International Continence Society (ICS) ICSmale questionnaire was devised to provide a thorough evaluation of the occurrence and bothersomeness of lower urinary tract symptoms and their impact on the lives of men with benign prostatic disease. This report completes the developmental work on the questionnaire, producing the concise short form instrument, ICSmaleSF, with a valid, reliable and scientifically justified scoring system. MATERIALS AND METHODS: Two data sets were used. The short form version of the questionnaire was devised and initially evaluated using data on men with uncomplicated lower urinary tract symptoms who were involved in the CLasP randomized controlled trial comparing laser therapy with transurethral prostatic resection and conservative management or monitoring without active intervention. External validation of the scoring system was undertaken using data from phase II of the ICS benign prostatic hyperplasia (BPH) study, an observational study of outcome in men with lower urinary tract symptoms related to benign prostatic enlargement. All patients completed the developmental version of the ICSmale questionnaire. Parallel analysis on the CLasP data set identified items that were responsive to change or highly problematic, allowing other redundant and overlapping items to be eliminated. Factor analysis and Cronbach's alpha coefficients were used to examine the clustering of items. Regression models were used to investigate the validity of followup scores within and across treatment groups in the CLasP and ICS/BPH studies. RESULTS: The questionnaire, which originally comprised 22 items, was shortened to 11 items in the 2 distinct factors of voiding (ICSmaleVS) and incontinence (ICSmaleIS) symptoms. Cronbach's alpha coefficients were high at 0.76 for ICSmaleVS and 0.78 for ICSmaleIS. A simple additive score was calculated by adding the 5 items in ICSmaleVS and 6 in ICSmaleIS. ICSmaleVS and ICSmaleIS detected expected improvement in the laser therapy and transurethral prostatic resection groups, and stability in the conservative management group within CLasP. Similarly each subscore but particularly ICSmaleVS was sensitive to differences in the outcome of the range of treatments in the ICS/BPH study. While frequency and nocturia were highly problematic and sensitive to change individually, they did not load into the other main factors or correlate with each other. It is suggested that these symptoms should be evaluated separately with the additional inclusion of a single item measure of the impact of lower urinary tract symptoms on daily life. CONCLUSIONS: The ICSmaleSF represents a comprehensive, concise, valid and reliable instrument for evaluating men with lower urinary tract symptoms. Unlike other questionnaires in the field it contains subscores for the domains of voiding and incontinent symptoms as well as the separate consideration of frequency, nocturia and impact on daily life. We hope that it will become the tool of choice for the comprehensive evaluation of treatment of men with lower urinary tract symptoms associated with benign prostatic disease.
Humans↗
Trace elements and inflammation.
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Humans↗
Application of a quality of life measure, the life situation survey (LSS), to alcohol-dependent subjects in relapse and remission.
BACKGROUND: Recent studies have shown that quality of life (QOL) is improved significantly when subjects do not relapse to heavy drinking, and QOL deteriorates significantly on prolonged relapse. This article further investigates these relationships using a QOL index, the Life Situation Survey (LSS). METHODS: Eighty-two DSM-IV alcohol-dependent subjects admitted for alcohol detoxification were studied at baseline and 12 week follow-up. Sociodemographic data were collected, and severity of alcohol dependence (SADQ) and General Health Questionnaire (GHQ-12) were baseline indices only. The main outcome measure, the LSS, was administered at both time points. RESULTS: Two subjects were lost to follow-up and one died during the study period. Thus, the relapse/ nonrelapse analysis related to 79 subjects. Fifty subjects (63%) had relapsed to heavy drinking at 3 months follow-up. There was a significant correlation between LSS and GHQ-12 scores. Significant changes occurred in total LSS scores as a result of relapse and nonrelapse. The improvement in LSS scores associated with nonrelapse was larger than the deterioration that accompanied relapse. In those subjects who did not relapse to heavy drinking, the mean follow-up score remained in the poor/borderline LSS range. Remission from heavy drinking was accompanied by significant improvements in appetite, sleep, and self-esteem. Relapse to heavy drinking coincided with a significant deterioration in mood/affect, public support, and work/life role scores. CONCLUSION: QOL as assessed by the LSS in recently detoxified alcoholics is impaired significantly. In the nonrelapse group, there was a significant improvement in LSS scores after 3 months. Relapse was accompanied by a smaller deterioration in LSS scores. The LSS can play an important role in monitoring the clinical care and progress of alcohol-dependent subjects.
Alcoholism↗
Carbonyl levels in type I and II fiber-rich muscles and their response to chronic ethanol feeding in vivo and hydroxyl and superoxide radicals in vitro.
BACKGROUND: Chronic alcoholic myopathy is characterized by selective reductions in the size of Type II skeletal muscle fibers (i.e., glycolytic, anaerobic fast-twitch). Type I (i.e., oxidative, aerobic, slow twitch) fibers are relatively resistant. It is possible that reactive oxygen species may preferentially damage the Type II fibers because the concentrations of several antioxidant enzymes are lower in Type II compared with Type I fibers. METHODS: To test the hypothesis, we measured protein carbonyl levels in Type I (i.e., soleus) and Type II (i.e., plantaris) fiber-rich muscles of rats subjected to chronic alcohol dosage with the Lieber-DeCarli regimen. Muscles were also exposed to hydroxyl or superoxide radicals in vitro. RESULTS: The Type I fiber-predominant soleus of control animals had less carbonyl than the Type II fiber-predominant plantaris. In rats that were fed ethanol for 6 weeks, the weights of the plantaris muscle were preferentially reduced but changes in soleus weight did not achieve significance. However, carbonyl levels were not significantly altered in any muscle in response to alcohol feeding. Calculation of the data in terms of total carbonyl per whole muscle showed decreases in both soleus and plantaris at the end of the 6-week alcohol feeding period. In response to hydroxyl radical (OH*) generation in vitro, protein carbonyl increased substantially in both soleus and plantaris muscles, but more so in the soleus. The increase in carbonyl in control soleus muscles in response to OH* was significantly lower than in soleus muscles from alcohol-fed animals. The increase in control plantaris muscle was not significantly different from the increase in carbonyl in corresponding muscles from ethanol-fed rats in response to OH*. In response to superoxide radicals, carbonyl in control soleus increased, an effect similar to that recorded in the soleus from ethanol-fed rats. In control plantaris, carbonyl increased in response to superoxide radicals, an effect not significantly different to the increase in plantaris from alcohol-fed rats. CONCLUSIONS: Using increased carbonyl concentrations as an indicator of muscle damage by reactive oxygen species, we concluded (1) there is no evidence of enhanced reactive oxygen species-induced damage to mixed muscle proteins in either Type I or Type II muscles in response to alcohol feeding; (2) Type II muscles have a greater capacity than Type I muscles to protect against damage (as indicated by carbonyl formation) by both hydroxyl and superoxide radicals in vitro; (3) alcohol reduces the capacity of Type I muscle to resist hydroxyl radical-induced protein damage, a mechanism that may arise through impairment of other antioxidant systems or other process not yet elucidated.
Alcoholism↗
Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice.
The hypotransferrinemic mouse (trf (hpx)) is a mutant strain exhibiting transferrin deficiency, marked anemia, hyperabsorption of iron, and elevated hepatic iron stores. We set out to investigate the relative roles of anemia and of transferrin in the malregulation of intestinal iron absorption in these animals. Transfusion of erythrocytes obtained from littermate controls increased hemoglobin levels and reduced reticulocyte counts in recipient animals. Although mucosal to carcass (59)Fe transfer was reduced, total duodenal iron uptake was not significantly affected. Iron absorption in homozygotes, in contrast to littermate controls, was not reduced by hyperoxia. Mouse transferrin injections, in the short term, increased delivery of iron to the marrow and raised hemoglobin levels. Although mucosal transfer and total iron uptake were reduced at the higher transferrin doses, total uptake was still higher than in controls. Daily injections of mouse/human transferrin for 3 weeks from weaning, normalized hemoglobin values, and markedly reduced liver iron and intestinal iron absorption values in trf (hpx) animals. When such daily-injected mice were left for a week to allow transferrin clearance, iron absorption values were significantly enhanced; hemoglobin or hepatic iron levels were, however, not significantly altered. These data indicate that hyperabsorption of iron in trf (hpx) mice is not solely because of the anemia; transferrin levels per se do affect iron absorption, possibly via a direct effect on the intestinal mucosa.
Anemia↗
An alarming lack of public awareness towards oral cancer.
OBJECTIVE: To determine public awareness and knowledge of oral cancer in Great Britain. DESIGN: The respondents were selected according to a systematic probability sample designed to be representative of all adults in Great Britain (GB). The overall design was similar to previous omnibus surveys carried out by National Opinion Poll (NOP). The survey was carried out in ten regions of GB in September 1995 and was commissioned by the Health Education Authority (HEA). SUBJECTS AND METHODS: A random sample of 1,894 members of the public over the age of 16 years were asked in face-to-face interviews their knowledge relating to cancer, with particular reference to oral cancer, its causes and those at high risk and general attitudes to cancer. RESULTS: Oral cancer was one of the least heard of cancers by the public with only 56% of the participants being aware, whereas 96% had heard of skin cancer, 97% lung cancer and 86% cervical cancer. There was a 76% awareness of the link between smoking and oral cancer but only 19% were aware of its association with alcohol misuse. Whereas 94% agreed that early detection can improve the treatment outcome, a disheartening 43% believed that whether a person developed a cancer or not was a matter of chance and therefore was unavoidable. CONCLUSIONS: This survey highlights a general lack of awareness among the public about mouth cancer and a lack of knowledge about its causation especially the excess risk associated with alcohol. RECOMMENDATIONS: There is a clear need to inform and educate the public in matters relating to the known risk factors associated with oral cancer. A media campaign informing the public about oral cancer is clearly required. The need for the reduction in the incidence of oral cancer should be included in 'Our healthier nation' targets. An overall health promotion strategy to reduce cancers should include oral cancer as a priority. In addition the European Code against Cancer which aims to improve prevention, the early detection of oral cancer and the necessity for fast track referral should be made more widely known. Recognition of oral cancer in local strategies for oral health should be encouraged.
Adolescent↗
Areca nuts can have deleterious effects.
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Areca↗
Population requirement for primary hip-replacement surgery: a cross-sectional study.
BACKGROUND: There has been a long-standing failure in many countries to satisfy the demand for several elective surgical treatments, including total hip replacement. We set out to estimate the population requirement for primary total hip replacement in England. METHODS: We undertook a cross-sectional study of a stratified random sample of 28,080 individuals aged 35 and over from 40 general practices in inner-city, urban, and rural areas of Avon and Somerset, UK. Prevalent disease was identified through a two-stage process: a self-report screening questionnaire (22,978 of 26,046 responded) and subsequent clinical examination. Incident disease was estimated from the point prevalence by statistical modelling. The requirement for total hip replacement surgery was estimated on the basis of pain and loss of functional ability, with adjustment for evidence of comorbidity and patients' treatment preferences. FINDINGS: 3169 people reported hip pain on the screening questionnaire. 2018 were invited for clinical examination, and 1405 attended. The prevalence of self-reported hip pain was 107 per 1000 (95% CI 101-113) for men and 173 per 1000 (166-180) for women. The prevalence of hip disease severe enough to require surgery was 15.2 (12.7-17.8) per 1000 aged 35-85 years. The corresponding annual incidence of hip disease requiring surgery was estimated as 2.23 (1.56-2.90), which suggests an overall requirement in England of 46,600 operations per year for patients who expressed a preference for, and were suitable for, surgery; the recent actual provision in England was about 43,500. INTERPRETATION: This research suggests that the satisfaction of demand for total hip replacement, given agreed criteria for surgery, is a realistic objective.
Adult↗
Early surgery compared with watchful waiting for glue ear and effect on language development in preschool children: a randomised trial.
BACKGROUND: Otitis media with effusion (OME) is the most common cause of hearing loss in children and is generally treated by elective surgery. We compared in children with persistent OME the effect on speech and language development of immediate surgery (ventilation-tube insertion) and watchful waiting before surgery. METHODS: We did a randomised controlled trial with masked outcome assessment in Bristol Children's Hospital, Bristol, UK. We included 186 children born between April 1, 1991, and Dec 31, 1992, who had confirmed bilateral OME and bilateral hearing impairment of 25-70 dB of at least 3 months' duration. Children were randomly assigned surgery within 6 weeks (n=92), or 9 months of watchful waiting (n=90), after which bilateral tube insertion was done if required. We assessed hearing loss, expressive language, and verbal comprehension at 9 months and 18 months. FINDINGS: At 9 months, standardised scores for expressive language and verbal comprehension differed between groups with marginal significance after adjustment for baseline differences (p=0.04 and p=0.028, respectively). At 9 months, verbal comprehension and expressive language skills in the watchful-waiting group were 3.24 months behind those in the early-surgery group. The watchful-waiting group was delayed on these two measures compared with their age-expected levels. 18 months after randomisation, 85% of children in the watchful-waiting group had received surgery and groups did not differ significantly. INTERPRETATION: There is some benefit from ventilation-tube insertion for expressive language and verbal comprehension but the timing of surgery is not critical.
Acoustic Impedance Tests↗
Substance misuse in early pregnancy and relationship to fetal outcome.
UNLABELLED: To establish the frequency of substance misuse in early pregnancy in an urban UK population, 807 consecutive positive pregnancy test urine samples were screened for a range of drugs, including cotinine as an indicator of maternal smoking habits. A positive test for cannabinoids was found in 117 (14.5%) samples. Smaller numbers of samples were positive for other drugs:- opiates (11), benzodiazepines (4), cocaine (3) and one each for amphetamines and methadone. Polydrug use was detected in nine individuals. Only two samples tested positive for ethanol. The proportion with a urine cotinine level indicative of active smoking was 34.3%. The outcome of the pregnancy was traced for 288 subjects. Cannabis use was associated with a lower gestational age at delivery (P < 0.005), an increased risk of prematurity (P < 0.02) and reduction in birth weight (P < 0.002). Whilst maternal smoking was associated with a reduction in infant birth weight (P < 0.05), this was less pronounced than the effect of other substance misuse. CONCLUSION: This study suggests that one in six women in South London are using drugs in early pregnancy and that cannabinoid use is associated with a poorer pregnancy outcome.
Female↗
Differentiation-dependent expression of gelatinase B/matrix metalloproteinase-9 in trophoblast cells.
The purpose of this study was to evaluate the Rcho-1 trophoblast culture system as a model for studying trophoblast invasion and to examine stage-specific expression of enzyme(s) potentially participating in rat trophoblast giant cell invasive behavior. The invasive behavior of the differentiating Rcho-1 trophoblast cells was demonstrated using Matrigel invasion chambers. Gelatin zymography and Western blot analysis of conditioned medium from differentiating Rcho-1 trophoblast cell cultures and rat ectoplacental cone outgrowths revealed a differentiation-dependent increase in gelatinase B/matrix metalloproteinase (MMP-9). Nothern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses of Rcho-1 trophoblast or ectoplacental cone cells also showed increasing expression of MMP-9 accompanying cell differentiation. Rcho-1 trophoblast cells stably transfected with MMP-9 promoter/luciferase reporter constructs exhibited a differentiation-dependent increase in MMP-9 promoter activation. In conclusion, trophoblast giant cell differentiation is characterized by transcriptional activation of the MMP-9 gene and appearance of the invasive phenotype.
Animals↗