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Biomedical subjects

A Ramirez

Publications and source records attributed to A Ramirez.

At least 19 recordsLinked to original sources
PubMed2006

Conditional ablation of C/EBP beta demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis.

The CCAAT/enhancer binding protein beta (C/EBP beta) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBP beta (C/EBP beta(-/-)) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBP beta(-/-) mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBP beta to specific phenotypes, mice with a conditional 'floxed' C/EBP beta null allele were generated. Epidermal-specific deletion of C/EBP beta was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBP beta(-/-) mice, K5-Cre;C/EBP beta(fl/fl) mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBP delta, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBP beta in skin tumor development. Our findings demonstrate that C/EBP beta exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBP beta in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK.

Focal adhesion kinase (FAK) is a critical component in transducing signals downstream of both integrins and growth factor receptors. To determine how the loss of FAK affects the epidermis in vivo, we have generated a mouse model with a keratinocyte-restricted deletion of fak (FAKK5 KO mice). FAK(K5 KO) mice displayed three major phenotypes--irregularities of hair cycle, sebaceous glands hypoplasia, and a thinner epidermis--pointing to defects in the proliferative capacity of multipotent stem cells found in the bulge. FAK-null keratinocytes in conventional primary culture undergo massive apoptosis hindering further analyses, whereas the defects observed in vivo do not shorten the mouse lifespan. These results suggest that the structure and the signaling environment of the native tissue may overcome the lack of signaling through FAK. Our findings point to the importance of in vivo and three-dimensional in vitro models in analyses of cell migration, proliferation, and survival. Surprisingly, the difference between FAKloxP/+ and FAKK5 KO mice in wound closure was not statistically significant, suggesting that in vivo loss of FAK does not affect migration/proliferation of basal keratinocytes in the same way as it affects multipotent stem cells of the skin.

Animals↗
PubMed2006

Time course of intraoperative cytokine levels in liver transplant recipients.

We evaluated the levels of several cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, tumor necrosis factor [TNF]-alpha, and interferon [IFN]-gamma) in plasma samples obtained before surgical intervention (T0) and during intraoperative liver transplantation: after induction of anesthesia (I-1), 15 minutes of anhepatic phase (I-2), 5 minutes before reperfusion (I-3), 10 minutes after reperfusion (I-4), 20 minutes after reperfusion (I-5), 60 minutes after reperfusion (I-6), and 1 hour after liver transplantation (I-7). Cytokine levels were determined using a technique which combines ELISA technique and flow cytometry. The study was approved by the local clinical research (ethics) committee. Written informed consent was obtained from patients' relatives. Twenty patients (14 men, 6 women) aged 23 to 61 years, recipients of a liver transplantation were studied. The cytokine IL-2 plasma values were maintained during the whole study period, with a slight increase at 15 minutes of anhepatic phase (I-2). IL-4 showed a peak value 20 minutes after reperfusion (I-5). IL-6 increased its plasma value starting at 15 minutes of anhepatic phase (I-2), maintaining high concentrations during the whole intraoperative period. IL-10 increased progressively, reaching a maximum 1 hour after transplantation (I-7). TNF-alpha reached maximum plasma levels 20 minutes after reperfusion (I-5), whereas IFN-gamma showed a peak at 15 minutes of anhepatic phase (I-2). Our results indicate that the anhepatic phase (I-2) is the earliest phase during which proinflammatory and anti-inflammatory cytokines, such as IL-6 and IL-10, respectively, are involved during liver transplantation. We conclude that IL-6 is the first cytokine involved in the inflammatory response during liver transplantation.

Adult↗
PubMed2005

The 2001 epidemic of foot-and-mouth disease in the United Kingdom: epidemiological and meteorological case studies.

The possibility of the airborne spread of foot-and-mouth disease during the 2001 epidemic in the uk has been investigated in three epidemiological case studies. On the basis of evidence from field investigations, and a simple meteorological analysis, it is concluded that the spread of disease was consistent with the airborne transport of virus. The distances ranged from less than 1 km to 16 km; six of the farms were over 6 km from the source and involved the passage of virus over the sea combined with meteorological conditions which strongly favoured airborne disease transmission. The results of detailed atmospheric modelling demonstrated that airborne virus could have challenged livestock on all the farms studied. However, with one exception the 24-hour average daily concentrations of the virus were significantly below the experimentally estimated threshold for infection. A detailed model intercomparison established that, under stable atmospheric conditions, peak concentrations of virus up to two orders of magnitude higher might have been experienced for short periods, owing to fluctuations within the plume of virus, and model limitations. This finding would significantly reduce the apparent discrepancy between the experimentally estimated threshold for infection and the modelling results.

Air Microbiology↗
PubMed2005

Efficient engraftment of in utero transplanted mice with retrovirally transduced hematopoietic stem cells.

Using an experimental mouse model, we have investigated the kinetics of hematopoietic reconstitution of recipients transplanted during fetal development with fresh and transduced hematopoietic stem cells (HSCs). Total bone marrow (BM) and purified Lin(-)Sca-1(+) cells, either fresh or transduced ex vivo with enhanced green fluorescent protein (EGFP)-encoding retroviral vectors, were in utero transplanted (IUT) into fetal mice. Data obtained 2 months after transplantation showed a similar proportion of engrafted animals, regardless of the fact that samples were purified or not on HSCs, and subjected or not to ex vivo transduction with retroviral vectors. The transplantation of grafts enriched in HSCs, either fresh or transduced, always improved the levels of donor chimerism of IUT mice in comparison with results obtained in mice transplanted with unpurified BM grafts (6.8 and 7.3% versus 1.15% median values, respectively). Significantly, engrafted recipients that were transplanted with the transduced graft always contained transduced EGFP(+) cells in peripheral blood (around 5% of donor cells were EGFP(+) at 2 months post-transplantation). This proportion was essentially maintained at longer times post-transplantation, as well as in secondary recipients transplanted with the BM of IUT mice. Our study describes for the first time a significant and stable engraftment of unconditioned mice subjected to IUT with HSCs transduced with retroviral vectors.

Animals↗
PubMed2005

The blood supply of the common peroneal nerve in the popliteal fossa.

We investigated the blood supply of the common peroneal nerve. Dissection of 19 lower limbs, including six with intra-vascular injection of latex, allowed gross and microscopic measurements to be made of the blood supply of the common peroneal nerve in the popliteal fossa. This showed that a long segment of the nerve in the vicinity of the fibular neck contained only a few intraneural vessels of fine calibre. By contrast, the tibial nerve received an abundant supply from a constant series of vessels arising directly from the popliteal and posterior tibial arteries. The susceptibility of the common peroneal nerve to injury from a variety of causes and its lack of response to operative treatment may be explained by the tenuous nature of its intrinsic blood supply.

Humans↗
PubMed2004

Major depression in outpatients attending a regional cancer centre: screening and unmet treatment needs.

A screening programme designed to identify cases of Major Depressive Disorder (MDD) in patients attending a Regional Cancer Centre outpatient department was established. It comprised two stages: (1) The Hospital Anxiety and Depression Scale (HADS) self-rating questionnaire administered by a touch-screen computer; (2) we interviewed patients with high scores on the HADS (15 or more total score) over the telephone using the depression section of the Structured Clinical Interview for DSMIV (SCID). A large consecutive sample (5613) of oncology clinic attenders was screened, and practical difficulties in the screening process were identified. The estimated prevalence of major depressive disorder (MDD) in the sample surveyed was approximately 8% (7.8%; 95% confidence intervals 6.9-8.5%). We assessed a consecutive series of 150 patients identified as having MDD to determine how many had received evidence-based treatment for MDD. Only half had discussed their low mood with their general practitioner, only one-third had been prescribed any antidepressant medication, and very few had taken a therapeutic dose for an adequate period. Very few had received psychological treatment or had been referred to mental health services. Most were receiving no potentially effective therapy.

Adult↗
PubMed2003

Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease.

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.

Administration, Inhalation↗
PubMed2002

Changes in psychological distress after cancer genetic counselling: a comparison of affected and unaffected women.

This study sought to examine changes in psychological distress following cancer genetic counselling. Women attending a family cancer clinic completed questionnaires before their appointment and at 2 weeks, 6 months and 12 months after their appointment. Twenty-six women were at low risk of developing breast or ovarian cancer, 76 were at moderate risk, 46 were at high risk and 46 women had previously had breast or ovarian cancer. All groups were compared with regard to measures of anxiety, depression, general psychological distress, worry about developing breast and ovarian cancer, and perceived risk of developing breast/ovarian cancer and perceived likelihood of carrying a genetic mutation. General psychological distress did not change over the course of the study and the groups did not differ on these measures. Worry about developing breast cancer and perceptions of the likelihood of carrying a genetic mutation significantly reduced following genetic counselling. On the whole women who had already had breast/ovarian cancer showed more concerns about ovarian cancer and raised perceptions of risk in comparison with the other groups, indicating the need for sensitive counselling of such women.

Anxiety↗
PubMed2002

Improving the working lives of cancer clinicians.

Cancer clinicians have to deal with particular difficulties in their work, including emotionally demanding interactions with patients and a high proportion of patients in whom curative treatment is ineffective. Perhaps, surprisingly, cancer clinicians are at no greater risk of poor mental health than other specialists, although levels among senior doctors are higher than among the employed general population. Being young, being single, feeling inadequately trained in communication and management skills and experiencing high levels of stress at work increase the risk of poor mental health for cancer clinicians and other senior doctors alike. Job satisfaction is important in that it appears to protect the mental health of cancer clinicians. Further work is required using a longitudinal approach to clarify risk factors. There is also a need to examine factors such as stress outside work that are likely to confer risk. We also need to understand how symptoms of poor mental health impair work performance. Having identified the risk factors, we need to begin to formulate interventions to improve the working lives of cancer clinicians through, for example, initiatives to improve communication and management skills, provide support to new consultants and facilitate teamwork.

Burnout, Professional↗
PubMed2001

Relativistic effects and two-body currents in (H)((-->)e(')p)n using out-of-plane detection.

Measurements of the (2)H((-->)e,e(')p)n reaction were performed with the out-of-plane magnetic spectrometers (OOPS) at the MIT-Bates Linear Accelerator. The longitudinal-transverse, f(LT) and f(')(LT), and the transverse-transverse, f(TT), interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q2 = 0.15 (GeV/c)(2). In comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions and the importance of two-body meson-exchange currents and isobar configurations. We demonstrate that such effects can be disentangled by extracting these responses using the novel out-of-plane technique.

Journal Article↗
PubMed2001

Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family.

The SLC26 gene family (solute carrier family 26) comprises five mammalian genes that encode anion transporter-related proteins. In addition to sat-1 and prestin, which were cloned from rat and gerbil, respectively, three human members have been identified and associated with specific genetic diseases (DTD, diastrophic dysplasia; CLD, congenital chloride diarrhea; PDS, Pendred syndrome). In this study we used a homology approach combined with RACE PCR to identify human SLC26A6, the sixth member of this gene family. Northern blot analysis showed the highest SLC26A6 transcript levels in kidney and pancreas. Expression in MDCK cells and in Xenopus oocytes demonstrated trafficking of the SLC26A6 protein to the cell membrane but did not reveal anion transport activity with tracer uptake or intracellular pH measurements. We determined the genomic structure of the SLC26A6 gene and excluded mutations in the 21 coding exons as the cause of DFNB6 and USH2B, which closely map to the SLC26A6 chromosomal locus (3p21).

Amino Acid Sequence↗
PubMed2001

HPLC-based method using sample pre-column clean-up for the determination of methanethiol and ethanethiol in parenteral amino acid solutions.

A method has been developed for the chromatographic determination of methanethiol (MT) and ethanethiol (ET) as contaminants in amino acid parenteral nutrition (PN) solutions. The clean-up of the samples before chromatographic analysis was investigated by solid-phase extraction (SPE) on pre-columns filled with polyethylene powder (PE), aluminium oxide (AlOx), silica (SiOx), or polyurethane foam (PUF) as adsorbents. The thiols were more efficiently separated from the matrices by SPE on PUF pre-columns. Simultaneous derivatization and elution with DTNB (5,5'-dithiobis(2-nitrobenzoic acid)) enabled further discrimination between MT and ET by reversed-phase HPLC with spectrophotometric detection. The retention times for the derivatized MT and ET species were 12.5 and 23.0 min, respectively. Recoveries from spiked PN samples were calculated to be approximately 90%, and the MT and ET content of commercial PN solutions was determined using the methodology described. Detection limits of 15 and 10 microg L(-1) were calculated for MT and ET, respectively.

Aluminum Oxide↗
PubMed2001

Dilatation and curettage fails to detect most focal lesions in the uterine cavity in women with postmenopausal bleeding.

OBJECTIVE: To determine the prevalence of focally growing lesions in the uterine cavity in women with postmenopausal bleeding and endometrium > or = 5 mm and the extent to which such lesions can be correctly diagnosed by D&C. METHODS: In a prospective study, 105 women with postmenopausal bleeding and endometrium > or = 5 mm at transvaginal ultrasound examination underwent diagnostic hysteroscopy, D&C and hysteroscopic resection of any focally growing lesion still left in the uterine cavity after D&C. Twenty-four women also underwent hysterectomy. If the histological diagnosis differed between specimens from the same patient, the most relevant diagnosis was considered the final one. RESULTS: Eighty percent (84/105) of the women had pathology in the uterine cavity, and 98% (82/84) of the pathological lesions manifested a focal growth pattern at hysteroscopy. In 87% of the women with focal lesions in the uterine cavity, the whole or parts of the lesion remained in situ after D&C. D&C missed 58% (25/43) of polyps, 50% (5/10) of hyperplasias, 60% (3/5) of complex atypical hyperplasias, and 11% (2/19) of endometrial cancers. The agreement between the D&C diagnosis and the final diagnosis was excellent (94%) in women without focally growing lesions at hysteroscopy. CONCLUSION: If there are focal lesions in the uterine cavity, hysteroscopy with endometrial resection is superior to D&C for obtaining a representative endometrial sample in women with postmenopausal bleeding and endometrium > or = 5 mm.

Adult↗