bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dicistronic MLV-retroviral vectors transduce neural precursors in vivoand co-express two genes in their differentiated neuronal progeny
Authors: Derrington Edmund A , López-Lastra Marcelo , Darlix Jean-Luc 
Published: September 2005

Abstract
Dicistronic MLV-based retroviral vectors, in which two IRESes independently initiate the translation of two proteins from a single RNA, have been shown to direct co-expression of proteins in several cell culture systems. Here we report that these dicistronic retroviral vectors can drive co-expression of two gene products in brain cells in vivo. Injection of retroviral vector producer cells leads to the transduction of proliferating precursors in the external granular layer of the cerebellum and throughout the ventricular regions. Differentiated neurons co-expressing both transgenes were observed in the cerebellum and in lower numbers in distant brain regions such as the cortex. Thus, we describe an eukaryotic dicistronic vector system that is capable of transducing mouse neural precursors in vivo and maintaining the expression of genes after cell differentiation.
Impact of HIV/AIDS on care and outcomes of severe sepsis
Authors: Mrus Joseph M , Braun LeeAnn , Yi Michael S , Linde-Zwirble Walter T , Johnston Joseph A 
Published: September 2005

Abstract
Introduction
There has been dramatic improvement in survival for patients with HIV/AIDS; however, some studies on patients with HIV/AIDS and serious illness have reported continued low rates of intensive care. The purpose of this study was to examine patterns of care and outcomes for patients with severe sepsis and HIV/AIDS and compare them with those of patients with severe sepsis without HIV/AIDS.

Methods
We assessed data from all 1999 discharge abstracts from all non-federal hospitals in six US states. Patient demographic characteristics, discharge diagnoses, resource use, and outcomes were extracted. Analyses were performed using chi-square, Wilcoxon rank sum, or regression techniques, as appropriate.

Results
We identified 74,020 patients with severe sepsis (7,638 (10.3%) had HIV/AIDS) using ICD-9-CM codes. Patients with severe sepsis and HIV/AIDS had a similar mean length of stay (16.9 days versus 17.7 days; p = 0.0669), had lower mean hospitalization cost ($24,382 versus $30,537; p < 0.0001), were less likely to be admitted to the intensive care unit (37% versus 56%; p < 0.0001), and had a greater mortality (29% versus 20%; p < 0.0001) than those without HIV/AIDS. After adjustment for cohort differences, patients with severe sepsis and HIV/AIDS had increased likelihood of death (OR (95% CI) = 2.41 (2.23–2.61)) and were substantially less likely to be admitted to the intensive care unit (OR (95% CI) = 0.54 (0.51–0.59)). When compared with those with severe sepsis and HIV/AIDS, patients with severe sepsis without HIV/AIDS were universally more likely to be admitted to the intensive care unit, even when they had comorbid illnesses with equal or worse expected in-hospital mortality (e.g., metastatic cancer).

Conclusion
For patients with severe sepsis, there are differences in care and outcomes for those with HIV/AIDS. Further research is needed to examine the delivery of care for patients with severe sepsis and HIV/AIDS.
Postnatal stem cell survival: does the niche, a rare harbor where to resist the ebb tide of differentiation, also provide lineage-specific instructions?
Authors: Kindler Vincent 
Published: September 2005

AbstractPostnatal stem cells regulate the homeostasis of the majority of our tissues. They continuously generate new progenitors and mature, functional cells to replace old cells, which cannot assume the tissue function anymore and are eliminated. Blood, skin, gut mucosa, muscle, cartilage, nerves, cornea, retina, liver, and many other structures are regulated by stem cells. As a result of their ability to produce large numbers of functionally mature cells, postnatal stem cells represent a promising tool for regenerative therapy. Indeed, unmanipulated stem cells or their progeny amplified in vitro are already used in some clinical applications to restore the function of injured or genetically deficient tissues. However, despite our cumulating understanding concerning postnatal stem cells, many aspects of their functionality remain unclear. For instance, in most tissues, we cannot reliably define the phenotype of the postnatal stem cells sustaining its survival. We do not know to which extent the environment surrounding the stem cell—the niche—which is a key actor insuring stem cell self-maintenance, is also implicated in the maintenance of stem cell lineage specificity. Moreover, we have to clarify whether postnatal stem cells are capable of undertaking “transdifferentiation”, that is, the conversion of one cell type into another under physiological conditions. Answering these questions should help us to draw a more accurate picture of postnatal stem cell biology and should lead to the design of safe, effective therapies.
Peripheral arterial disease symptom subtype and walking impairment
Authors: Collins Tracie C , Petersen Nancy J , Suarez-Almazor Maria 
Published: September 2005

Walking impairment is common in patients with peripheral arterial disease (PAD). The purpose of this study was to compare specific leg symptoms and walking impairment in a racially diverse cohort of patients with PAD. Patients who were receiving care at the Michael E DeBakey Veterans Affairs Medical Center or in the Harris County Hospital District were screened for PAD, which was diagnosed in the office setting by blood pressure measurements that were used to calculate the ankle-brachial index (a level <0.90 was defined as disease). To define leg symptoms, we asked patients to complete the San Diego Claudication Questionnaire. Based on the questionnaire results, leg symptoms were categorized as: asymptomatic, atypical, and intermittent claudication. The patients also completed the Walking Impairment Questionnaire. Among 403 patients screened (136 Caucasians, 136 African Americans and 131 Latinos), 67 were found to have PAD (18 Caucasians, 31 African Americans and 18 Latinos). The mean age of the cohort was 63.8 years (standard deviation (SD) 7.3). Walking distance, speed and stair climbing scores were lower (p < 0.0001) for patients with PAD and leg pain on exertion or at rest when compared with patients with PAD without leg symptoms or with symptoms of intermittent claudication. For patients with PAD and leg pain on exertion and at rest, the walking distance score was 27.1 ± SD 37.7 compared with 41.0 ± 38.4 for those with asymptomatic disease who were inactive, and with 38.5 ± 42.7 for those with intermittent claudication ( p = 0.02). In an ethnically diverse primary care clinic population, patients with PAD and leg pain on exertion and at rest had greater compromise in their walking ability when compared with patients with intermittent claudication. The reasons for the significant impairment in walking among patients with PAD and these atypical leg symptoms may stem from coexisting illnesses or other as yet undefined factors. Future research should focus on methods to improve daily walking in patients with PAD and atypical leg symptoms.
Trauma in the anticoagulated patient
Authors: Guly HR , Jones LO , Nokes TJC 
Published: September 2005

An increasing number of people are taking anticoagulants for the prophylaxis of thromboembolic disease. This may cause problems when they attend hospital following trauma. Patients may also develop spontaneous bleeding that may have similar effects to bleeding after an injury. This article discusses the risks of bleeding (especially in head injury); the risks of stopping anticoagulation; how anticoagulation should be reversed and how anticoagulation should affect the approach to the head-injured patient.
Prefrontal white matter in pathological liars
Authors: Yang Yaling , Raine Adrian , Lencz Todd , Bihrle Susan , Lacasse Lori , Colletti Patrick 
Published: September 2005

BackgroundStudies have shown increased bilateral activation in the prefrontal cortex when normal individuals lie, but there have been no structural imaging studies of deceitful individuals.AimsTo assess whether deceitful individuals show structural abnormalities in prefrontal grey and white matter volume.MethodPrefrontal grey and white matter volumes were assessed using structural magnetic resonance imaging in 12 individuals who pathologically lie, cheat and deceive (‘liars’), 16 antisocial controls and 21 normal controls.ResultsLiars showed a 22–26% increase in prefrontal white matter and a 36–42% reduction in prefrontal grey/white ratios compared with both antisocial controls and normal controls.ConclusionsThese findings provide the first evidence of a structural brain deficit in liars, they implicate the prefrontal cortex as an important (but not sole) component in the neural circuitry underlying lying and provide an initial neurobiological correlate of a deceitful personality.
Schizophrenia and cancer: an epidemiological study
Authors: Goldacre Michael J. , Kurina Lianne M. , Wotton Clare J. , Yeates David , Seagroatt Valerie 
Published: September 2005

BackgroundFor decades there has been interest in the possibility that people with schizophrenia might have some protection against cancer, and that, if this were so, it might hold clues about aetiological mechanisms in schizophrenia.AimsTo study cancer incidence in schizophrenia.MethodCohort analysis of linked hospital and death records was used to compare cancer rates in people with schizophrenia with a reference cohort.ResultsWe did not find a reduced risk for cancer overall (rate ratio 0.99, 95% CI 0.90–1.08) or for most individual cancers. There was, however, a significantly low rate ratio for skin cancer (0.56, 95% CI 0.36–0.83)ConclusionsWe found no evidence that schizophrenia confers protection against cancer in general. Low rates of skin cancer are consistent with the hypothesis that sun exposure may influence the development of schizophrenia, although other explanations are also possible.
Family education for people with schizophrenia in Beijing, China
Authors: Li Zheng , Arthur David 
Published: September 2005

BackgroundMuch of China lacks well-developed services for people with schizophrenia and their families, and most of the existing services focus on hospitals. There is a need for culturally sensitive family treatments offered by nurses.AimsTo conduct a longitudinal experimental study examining the effect of patient and family education in a sample of Chinese people with schizophrenia.MethodA randomised controlled trial was conducted in a large hospital with a sample of 101 patients with schizophrenia and their families. Data were collected at admission and at discharge, and then at 3 and 9 months after discharge. The intervention group received family education, and data on their knowledge about schizophrenia, symptoms, functioning, psychosocial behaviour, relapse and medication adherence were collected and compared with the control group.ResultsThere was a significant improvement in knowledge about schizophrenia in the experimental group and a significant difference in symptom scores and functioning at 9 months after discharge. Patients who were non-adherent to medication regimens were more likely to relapse.ConclusionsFamily education on schizophrenia by nurses in China was effective in improving knowledge and promoting improvement in patients' symptoms.
In-patient treatment of opiate dependence: medium-term follow-up outcomes
Authors: Smyth Bobby P. , Barry Joe , Lane Alison , Cotter Mary , O'Neill Mary , Quinn Caroline , Keenan Eamon 
Published: September 2005

BackgroundThe outcome for opiate-dependent patients seeking abstinence is unclear in this era of improved access to methadone maintenance.AimsTo measure the outcome 2–3 years after in-patient treatment.MethodOpiate-dependent patients admitted with a goal of abstinence were followed-up. A structured interview examined drug use and treatment in the preceding month.ResultsFive patients had died and 109 (76%) of the remaining 144 were interviewed. Fifty per cent (54 patients) reported recent opiate misuse and 57% (62) were on methadone maintenance. Twenty-three per cent (25 patients) were abstinent (i.e. neither using opiates nor on methadone maintenance). Abstinence was significantly associated with completion of the 6-week in-patient treatment programme and attendance at out-patient after-care, and negatively associated with a family history of substance misuse.ConclusionsAbstinence remains an attainable goal. As the principal influence on outcome was treatment adherence, inpatient services should seek to enhance rates of programme completion. Aftercare should be provided to patients. We caution against use of pre-treatment patient characteristics as criteria for prioritising access to in-patient treatment.
Clinical implications of Brief Psychiatric Rating Scale scores
Authors: Leucht Stefan , Kane John M. , Kissling Werner , Hamann Johannes , Etschel Eva , Engel Rolf 
Published: September 2005

BackgroundDespite the widespread use of the Brief Psychiatric Rating Scale (BPRS), the clinical meaning of its total score and cut-off values used to define treatment response are unclear.AimsTo link the BPRS to Clinical Global Impression (CGI) ratings.MethodEquipercentile linking of BPRS and CGI ratings from seven drug trials in acutely ill patients with schizophrenia (n=1979).Results‘Mildly ill’ according to the CGI approximately corresponded to a BPRS total score of 31, ‘moderately ill’ to a BPRS score of 41 and ‘markedly ill’ to a BPRS score of 53. ‘Minimally improved’ according to the CGI score was associated with percentage BPRS reductions of 24, 27 and 30% at weeks 1, 2 and 4, respectively. The corresponding numbers for a CGI rating of ‘much improved’ were 44, 53 and 58%ConclusionsThe results provide a clearer understanding of how to interpret BPRS total and percentage reduction scores in clinical trials with patients acutely ill with schizophrenia who are experiencing positive symptoms.
Prevalence and predictors of mental incapacity in psychiatric in-patients
Authors: Cairns Ruth , Maddock Clementine , Buchanan Alec , David Anthony S. , Hayward Peter , Richardson Genevra , Szmukler George , Hotopf Matthew 
Published: September 2005

BackgroundLittle is known about the proportion of psychiatric in-patients who lack capacity to make treatment decisions, or the associations of lack of capacity.AimsTo determine the prevalence of psychiatric in-patients who lack capacity to make decisions about current treatment and to identify demographic and clinical associations with lack of mental capacity.MethodPatients (n=112) were interviewed soon after admission to hospital and a binary judgement of capacity was made, guided by the MacArthur Competence Tool for Treatment. Demographic and clinical information was collected from an interview and case notes.ResultsOf the 112 participants, 49 (43.8%) lacked treatment-related decisional capacity Mania and psychosis, poor insight, delusions and Black and minority ethnic group were associated with mental incapacity. Of the 49 patients lacking capacity, 30 (61%) were detained under the Mental Health Act 1983. Of the 63 with capacity, 6 (9.5%) were detained.ConclusionsLack of treatment-related decisional capacity is a common but by no means inevitable correlate of admission to a psychiatric in-patient unit.
Insulin-Like Growth Factor-I Signaling in Smooth Muscle Cells Is Regulated by Ligand Binding to the 177CYDMKTTC184 Sequence of the β3-Subunit of αVβ3
Authors: Maile Laura A. , Busby Walker H. , Sitko Kevin , Capps Byron E. , Sergent Tiffany , Badley-Clarke Jane , Clemmons David R. 
Published: September 2005

AbstractThe response of smooth muscle cells to IGF-I requires ligand occupancy of the αVβ3 integrin. We have shown that vitronectin (Vn) is required for IGF-I-stimulated migration or proliferation, whereas the anti-αVβ3 monoclonal antibody, LM609, which inhibits ligand binding, blocks responsiveness of these cells to IGF-I. The amino acids 177–184 (177CYDMKTTC184) within the extracellular domain of β3 have been proposed to confer the ligand specificity of αVβ3; therefore, we hypothesized that ligand binding to the 177–184 cysteine loop of β3 may be an important regulator of the cross talk between αVβ3 and IGF-I in SMCs. Here we demonstrate that blocking ligand binding to a specific amino acid sequence within the β3 subunit of αVβ3 (i.e. amino acids 177–184) blocked Vn binding to the β3 subunit of αVβ3 and correspondingly β3 phosphorylation was decreased. In the presence of this antibody, IGF-I-stimulated Shc phosphorylation and ERK 1/2 activation were impaired, and this was associated with an inhibition in the ability of IGF-I to stimulate an increase in migration or proliferation. Furthermore, in cells expressing a mutated form of β3 in which three critical residues within the 177–184 sequence were altered β3 phosphorylation was decreased. This was associated with a loss of IGF-I-stimulated Shc phosphorylation and impaired smooth muscle cell proliferation in response to IGF-I. In conclusion, we have demonstrated that the 177–184 sequence of β3 is necessary for Vn binding to αVβ3 and that ligand occupancy of this site is necessary for an optimal response of smooth muscle cells to IGF-I.
The Evolution of Mineralocorticoid Receptors
Authors: Hu Xiao , Funder John W. 
Published: September 2005

Abstract
When the human mineralocorticoid receptor (hMR) was cloned and sequenced by the Evans laboratory, its close homology with the human glucocorticoid receptor (hGR) was noted; subsequently, on the basis of its higher sequence similarity to the GR than to the progesterone receptor (PR) or androgen receptor (AR), MR and GR have commonly been considered to share an immediate common ancestral “corticoid receptor.” When, however, homology is determined for the full-length receptor, or helices 3/4/5/12, MR is least like any of the other three receptors; for the ligand binding domain, AR is clearly the least homologous. When relative binding and activation capacity of a broad panel of LXXLL cofactor peptides are compared by mammalian two-hybrid assay, GR and PR show a highly similar profile, interacting with many of the 39 peptides, with MR and AR binding very few, supporting a close functional homology between PR and GR. In addition, recent studies by He et al. on FXXLF binding by GR and PR mutants suggest that these two receptors may be closer to AR than to MR. The sequence and transcriptional activity of the S810L mutant reported by Geller et al. can be interpreted as supporting MR as being closer than GR/PR/AR to estrogen receptor/retinoid X receptor, and thus potentially the first rather than the last branch from a common MR/GR/PR/AR ancestor. On the basis of these studies together, we propose reconsideration of the evolutionary tree for the MR/GR/PR/AR subfamily, with MR closest to the primordial ancestral receptor, GR/PR sharing a common immediate ancestor, and a higher degree of evolutionary drift in the AR ligand binding domain to accommodate C19 rather than C21 steroids as physiological ligands.
Germfree status of mice obtained by embryo transfer in an isolator environment
Authors: Inzunza José , Midtvedt Tore , Fartoo Mona , Norin Elisabeth , Österlund Ewa , Persson Anna-Karin , Ährlund-Richter Lars 
Published: September 2005

The technique of embryo transfer has been evaluated for the purpose of changing the mouse stocks to a germfree (GF) status. Our results show reproducible and quality-assured conversion of animals to those which are negative for the presence of microorganisms. Rapid and easy access to GF mice is advantageous for studies of selected microflora and their cross-talks with the host, when applying, e.g. genomic, proteomic and metabolic methodology. The study involved embryo transfer in an isolator environment, thereby allowing implantation of cleansed embryos into GF recipients under well-controlled conditions. The recipient females gave birth normally and took care of the offspring as if they were their own pups, thus enhancing the survival rate. Access to full technical resources required to maintain GF isolators are, however, a prerequisite. In this study, we used stainless steel isolators designed by Gustafsson (1959), on which a stereomicroscope was mounted to facilitate embryo transfer inside the isolator. The use of embryo transfer and isolator techniques will facilitate the availability of various mouse mutant models under different gnotobiotic conditions, GF, monoxenic or polyxenic animals, to enable comparison with conventional animals for physiological and pathophysiological studies.
Optimization of the MB49 mouse bladder cancer model for adenoviral gene therapy
Authors: Loskog A , Ninalga C , Hedlund T , Alimohammadi M , Malmström P-U , Tötterman T H 
Published: September 2005

Bladder cancer is regarded as a promising candidate for innovative therapies in the field of immune and gene therapy. In this paper, we present the subcutaneous, metastatic and a novel orthotopic model of murine MB49 bladder cancer in C57BL/6 mice. We further show the potential of using adenoviral vectors together with different transduction enhancers to augment in vivo gene delivery. Finally, we present candidate genes for tumour detection, therapy or targeting. The MB49 tumour grew rapidly in mice. The subcutaneous model allowed for tumour detection within a week and the possibility to monitor growth rate on a day-by-day basis. Injection of MB49 cells intravenously into the tail vein gave rise to lung metastases within 16 days, while instillation of tumour cells into pretreated bladders led to a survival time of 20–40 days. Adenoviral vectors can be used as a vehicle for gene transfer to the bladder. By far, the most potent transduction enhancer was Clorpactin, also known as oxychlorosene. Last, we show that MB49 cells express tumour-associated antigens like bladder cancer-4, prostate stem cell antigen and six-transmembrane epithelial antigen of the prostate. Given the possibility for efficient genetic modification of the bladder and the presence of known tumour antigens, the MB49 models can be used in innovative ways to explore immunogene therapy.