Restoring the heart to homebirth.
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Biomedical subjects
Publications and source records attributed to J Hall.
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OBJECTIVE: To detail the biology and diagnostic usefulness of serum procalcitonin in critical illness. DATA SOURCES: A review of articles published in peer reviewed journals from 1990 to 2001 and identified through a MEDLINE search on procalcitonin. SUMMARY OF REVIEW: Procalcitonin (PCT) is a prohormone of calcitonin. Serum levels are elevated during sepsis and have been identified as a potential marker of infection in critical illness. However, its function and precise source of origin during sepsis remain unclear. The value of estimating serum PCT appears to be in the differentiation of infectious from non-infectious forms of systemic inflammatory response syndrome. A number of studies also point to its usefulness in distinguishing between bacterial and viral meningitis. However, there are a number of non-infectious conditions, where elevations in serum PCT occur, reducing its specificity. Its superiority as a marker of sepsis compared with other acute phase reactants continues to be debated. CONCLUSIONS: The utility of serum procalcitonin as a diagnostic test of sepsis is still under evaluation. Moreover, a number of unanswered questions remain regarding the biological role of PCT during sepsis, its target receptors and its protective value to the patient.
We report the complete sequence of an extreme halophile, Halobacterium sp. NRC-1, harboring a dynamic 2,571,010-bp genome containing 91 insertion sequences representing 12 families and organized into a large chromosome and 2 related minichromosomes. The Halobacterium NRC-1 genome codes for 2,630 predicted proteins, 36% of which are unrelated to any previously reported. Analysis of the genome sequence shows the presence of pathways for uptake and utilization of amino acids, active sodium-proton antiporter and potassium uptake systems, sophisticated photosensory and signal transduction pathways, and DNA replication, transcription, and translation systems resembling more complex eukaryotic organisms. Whole proteome comparisons show the definite archaeal nature of this halophile with additional similarities to the Gram-positive Bacillus subtilis and other bacteria. The ease of culturing Halobacterium and the availability of methods for its genetic manipulation in the laboratory, including construction of gene knockouts and replacements, indicate this halophile can serve as an excellent model system among the archaea.
Changes in iron supply to oceanic plankton are thought to have a significant effect on concentrations of atmospheric carbon dioxide by altering rates of carbon sequestration, a theory known as the 'iron hypothesis'. For this reason, it is important to understand the response of pelagic biota to increased iron supply. Here we report the results of a mesoscale iron fertilization experiment in the polar Southern Ocean, where the potential to sequester iron-elevated algal carbon is probably greatest. Increased iron supply led to elevated phytoplankton biomass and rates of photosynthesis in surface waters, causing a large drawdown of carbon dioxide and macronutrients, and elevated dimethyl sulphide levels after 13 days. This drawdown was mostly due to the proliferation of diatom stocks. But downward export of biogenic carbon was not increased. Moreover, satellite observations of this massive bloom 30 days later, suggest that a sufficient proportion of the added iron was retained in surface waters. Our findings demonstrate that iron supply controls phytoplankton growth and community composition during summer in these polar Southern Ocean waters, but the fate of algal carbon remains unknown and depends on the interplay between the processes controlling export, remineralisation and timescales of water mass subduction.
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Upregulated expression of bcl-xL is involved in the initiation and progression of breast cancer by inhibiting tumor cell apoptosis. Here we describe the use of the 2;-O-methoxy-ethoxy antisense oligonucleotide 4259 targeting nucleotides 687-706 of the bcl-xL mRNA, a sequence that does not occur in the pro-apoptotic bcl-xS transcript, to restore apoptosis in estrogen-dependent and independent breast carcinoma cells. The antisense effect of oligonucleotide 4259 was examined on the mRNA and protein level using real-time PCR and Western blot analysis, respectively, and the induction of cell death was investigated in viability and apoptosis assays. Treatment of MCF7 cells with oligonucleotide 4259 at a concentration of 600 nM for 20 hr decreased bcl-xL mRNA and protein levels by more than 80% and 50%, respectively. This resulted in the induction of apoptosis characterized by mitochondrial cytochrome c release, decrease of mitochondrial transmembrane potential, and the appearance of condensed nuclei in approximately 40% of cells. Moreover, oligonucleotide 4259 efficiently downregulated bcl-xL expression and decreased cell growth in the breast carcinoma cell lines T-47D, ZR-75-1, and MDA-MB-231. Our data emphasize the importance of bcl-xL as a survival factor for breast carcinoma cells and suggest that oligonucleotide 4259 deserves further investigations for use in breast cancer therapy.
BACKGROUND: The neurodevelopment of childhood anxiety disorders is not well understood. Basic research has implicated the amygdala and circuits related to these nuclei as being central to several aspects of fear and fear-related behaviors in animals. METHODS: Magnetic resonance imaging was used to measure amygdala volumes and comparison brain regions in 12 child and adolescent subjects with generalized anxiety disorder and 24 comparison subjects. Groups were matched on age, sex, height, and handedness and were also similar on measures of weight, socioeconomic status, and full scale IQ. RESULTS: Right and total amygdala volumes were significantly larger in generalized anxiety disorder subjects. Intracranial, cerebral, cerebral gray and white matter, temporal lobe, hippocampal, and basal ganglia volumes and measures of the midsagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: Although these data are preliminary and from a small sample, the results are consistent with a line of thinking that alterations in the structure and function of the amygdala may be associated with pediatric generalized anxiety disorder.
Over-expression of the anti-apoptotic protein bcl-xL is frequently found in lung cancer where it potentially contributes to tumor development, progression and drug resistance. To override the apoptotic block in lung-adenocarcinoma and small-cell-lung-cancer (SCLC) cells caused by over-expression of bcl-xL, an anti-sense oligodeoxynucleotide was designed targeting a sequence unique to the bcl-xL coding region and not shared by the pro-apoptotic splice variant bcl-xS. Moreover, to improve the biophysical properties of the anti-sense compound, 2;-methoxy-ethoxy modifications were made to selected deoxy-ribose residues. The resulting gapmer oligonucleotide 4259 was tested on lung-adenocarcinoma and SCLC cell lines in vitro. Treatment of the adenocarcinoma cell lines A549 and NCI-H125 and the SCLC cell lines SW2 and NCI-H69 with 600 nM 4259 reduced bcl-xL levels by 70 to 90%. In the lung-adenocarcinoma cell lines, apoptosis was induced, as indicated by caspase-3-like protease activation and nuclear condensation and fragmentation. In contrast, in the SCLC cell lines, no induction of apoptosis could be demonstrated. These findings imply that bcl-xL is a more critical survival factor for lung adenocarcinomas than for SCLC, and suggest the use of oligonucleotide 4259 for therapy of this major sub-type of lung cancer.
The surgical management of venous injuries in the popliteal fossa is a contested issue. The basic options are ligation or repair. Most anatomy textbooks briefly describe a single popliteal vein, and the literature contains few references on venous patterns in this region. Although the primary objective of this study was to analyze venous variability in 52 dissected cadaveric popliteal fossae and 63 venograms, data were also collected on the popliteal artery. Nine groups (A-I) were designated regarding the manner of formation of the popliteal vein. These groupings were based primarily on differences in the union of the anterior tibial, posterior tibial, and fibular (peroneal) veins to form medial and lateral (popliteal) veins, and whether these two veins fused to form a singular popliteal vein proximal or distal to the transverse plane at the level of the distal edge of the femoral condyles (FC). In the majority of the dissections and venograms, multiple veins crossed the FC, and the medial vein was larger in diameter than the lateral vein. Two patterns of popliteal artery termination were observed based on differences in the site of origin of the fibular artery. The results were compared with anatomy and vascular surgery textbook descriptions and sparse literature reports on vascular variations in the popliteal fossa. It is hoped that these data will benefit surgeons performing procedures in this region.
A study was conducted to assess the impact of court appointed experts on the judgments of mock jurors. A civil proceeding was adopted for the experiment. Mock jurors heard testimony about a plaintiff's injury in an automobile accident. In some conditions, medical testimony for the plaintiff and defendant was provided by experts hired by each side. In other conditions, a medical expert appointed by the court testified in addition to the two adversarial experts. In one of these conditions, the court expert sided with the plaintiff; in another, the expert sided with the defendant. The plaintiff in the case was always an individual. The defendant was sometimes a corporation and sometimes an individual. The results showed that mock jurors sided with the court appointed expert in every condition except when the expert favored a corporate defendant. The results were discussed in terms of heuristic processing of persuasive information.
In 1995, the state of Colorado began a new funding program for the provision of mental health services to Medicaid recipients. Medicaid funding was restructured from a fee-for-service system into a capitated managed care system. The restructuring altered the way in which mental health resources were allocated within Colorado's mental health system. This article explores the ethical principles inherent in the allocation of mental health resources within Colorado. The allocation system before and after the capitation pilot is analyzed according to three models of distributive justice. Under capitation, access to care corresponds to egalitarian ideals, while service delivery and outcomes follow a more utilitarian philosophy. Results from several empirical studies of the Colorado Medicaid system are used to support this ethical analysis. The analysis leads to the suggestion that the fair-opportunity rule may be a useful principle for developing just distribution systems in other states in the future.
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The genetic determinants for most breast cancer cases remain elusive. Whilst mutations in BRCA1 and BRCA2 significantly contribute to familial breast cancer risk, their contribution to sporadic breast cancer is low. In such cases genes frequently altered in the general population, such as the gene mutated in Ataxia telangiectasia (AT), ATM may be important risk factors. The initial interest in studying ATM heterozygosity in breast cancer arose from the findings of epidemiological studies of AT families in which AT heterozygote women had an increased risk of breast cancer and estimations that 1% of the population are AT heterozygotes. One of the clinical features of AT patients is extreme cellular sensitivity to ionising radiation. This observation, together with the finding that a significant proportion of breast cancer patients show an exaggerated acute or late normal tissue reactions after radiotherapy, has lead to the suggestion that AT heterozygosity plays a role in radiosensitivity and breast cancer development. Loss of heterozygosity in the region of the ATM gene on chromosome 11, has been found in about 40% of sporadic breast tumours. However, screening for ATM mutations in sporadic breast cancer cases, showing or not adverse effects to radiotherapy, has not revealed the magnitude of involvement of the ATM gene expected. Their size and the use of the protein truncation test to identify mutations limit many of these studies. This latter parameter is critical as the profile of mutations in AT patients may not be representative of the ATM mutations in other diseases. The potential role of rare sequence variants within the ATM gene, sometimes reported as polymorphisms, also needs to be fully assessed in larger cohorts of breast cancer patients and controls in order to determine whether they represent cancer and/or radiation sensitivity predisposing mutations.
This paper takes up a theoretical and empirical investigation of how two community-based projects for young women both create safety from community and domestic violence but how, in the process, discourses of multicultural inclusion define one site, and racist discourses of exclusion float through the other site. By relying on two intensive qualitative case studies of community-based organizations for girls, one exclusively White and working class and the other expressly multicultural and antiracist, we try to identify those structures and practices that support feminist, but inadvertently racist, work and those structures and practices that enable, at once, feminist and antiracist consciousness and praxis.
This paper reports the quality of life (QoL) of a large cohort of Australian women three and twelve months after surgery for early stage breast cancer (ESBC), and shows that the impact of disease and treatment on QoL differed by age, education and marital status. Eighty-three percent of eligible patients were recruited; 86% had breast conserving surgery and 14% mastectomy. Response rates were 93% (n = 305) at three months and 88% (n = 291) at one year. Quality of life was measured with the EORTC core questionnaire (QLQ-C30) and an ESBC-specific questionnaire. Multilevel analysis was used to estimate the effects and interactions of time, treatment and patient characteristics. Most symptoms declined between three months and one year, but arm and menopausal symptoms persisted. Emotional, social and role functioning improved over time, and fear of disease recurrence diminished. Younger women faired worse than older women on a broad range of QoL dimensions. Single women and those with less education faired worse on a number of dimensions. The negative impact of mastectomy on body image was greatest among married women, particularly young married women. These sociodemographic distinctions are relevant when discussing treatment options with women facing a diagnosis of ESBC.
The hippocampus is required for many forms of long-term memory in both humans and animals, and formation of long-lasting memories requires the synthesis of new proteins. Furthermore, the long-term potentiation (LTP) of hippocampal synapses, a widely studied model of memory, also depends on both de novo gene transcription and protein synthesis and results in the activation of transcription from promotors containing the cAMP response element (CRE). Expression of several genes is induced during the establishment of LTP; these include the immediate-early genes (IEGs) BDNF (brain-derived neurotrophic factor), zif268 and C/EBPbeta (CCAAT-enhancer binding protein beta), all of which contain CRE sites within their promotor regions. However, these genes induced by LTP are not known to be rapidly induced following learning in a natural setting. Here we demonstrate rapid and selective induction of BDNF expression during hippocampus-dependent contextual learning.