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PubMed2003

Alternatively spliced variants of Gallus gallus TNFRSF23 are expressed in the ovary and differentially regulated by cell signaling pathways.

As a result of searching recently available chicken (ch) expressed sequence tag databases, a new Tumor Necrosis Factor Receptor Super Family (TNFRSF) member with similarity to the murine (m) TNFRSF23 decoy receptor (DcR) has been identified. However, by comparison with the mTNFRSF23, there exist at least two splice variants of chTNFRSF23, one of which includes an intracellular death domain (TNFRSF23.v1) characteristic of death receptors, and the other with a truncated cytoplasmic domain of a DcR (named TNFRSF23.v2). These two splice variants of chTNFRSF23 display differential patterns of mRNA expression across various hen tissues, with the highest levels observed within reproductive tissues. More specifically, TNFRSF23.v1 is most highly expressed in preovulatory follicle granulosa cells in the ovary, whereas TNFRSF23.v2 mRNA is found at highest levels in ovarian stromal tissue. Primary culture experiments with granulosa cells determined that expression of TNFRSF23.v1 mRNA was decreased by protein kinase A signaling and enhanced by transforming growth factor (TGF) alpha treatment. Interestingly, TGFbeta1 and signaling via protein kinase C also enhanced levels of TNFRSF23.v1 expression but only in undifferentiated granulosa cells from prehierarchal follicles. Based on patterns of mRNA expression and its endocrine/paracrine regulation, we predict that ovarian chTNFRSF23 represents a modulator of granulosa cell survival and/or differentiation. Finally, the characterization of these receptor variants is of considerable interest from an evolutionary perspective in that they provide additional evidence to support a continuing divergence of TNFRSF members throughout vertebrate evolution.

Alternative Splicing↗

PubMedDate not supplied

Complete integration of inpatient and outpatient burn care: evolution of an outpatient burn clinic.

Burn centers are under continuing pressures to lower costs and maintain quality of care. One method of achieving this goal is to integrate inpatient and outpatient care in the burn unit. In 1991, our unit instituted an on-site outpatient clinic that was expanded significantly in 1996. The clinic is staffed by the inpatient personnel and allows for 24-hour availability and accommodation of all nurse and physician visits. The number of outpatient visits has increased from 1604 in 1992 to 4728 in 1996, despite a 33% reduction in registered nurse staffing during this time. From 1990 to 1996, the average length of inpatient stay for burns of 0% to 5% total burn surface area (TBSA), 6% to 10% TBSA, and 11% to 15% TBSA has decreased from 7.5 to 3.7 days, 10.3 to 7.7 days, and 16.6 to 11.8 days, respectively. Complete integration of inpatient and outpatient burn care can be achieved. An expanded on-site outpatient facility leads to optimal continuity of care, outpatient management of a larger percentage of burn injuries, and a shift in census from the inpatient to outpatient settings.

Burn Units↗

PubMed1995

Mercy Healthcare's CARE 2000: an evolution in progress.

In a learning environment of shared governance, continuous quality improvement, and redesign principle application, disciplines of Mercy Healthcare San Diego produced their patient care delivery redesign model, Creative Actions Reflecting Excellence. Nurses, pharmacists, medical technologists, respiratory care practitioners, physicians, educators, managers, and many other professional and technical partners converted change and transition into opportunities. As disciplines understood and appreciated each other's unique and shared contributions, quality of care, stakeholder satisfaction, and process efficiencies increased.

Decision Making, Organizational↗

PubMed2006

Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes.

Most genes are conserved in mammals, but certain gene families have acquired large numbers of lineage-specific loci through repeated rounds of gene duplication, divergence, and loss that have continued in each mammalian group. One such family encodes KRAB-zinc finger (KRAB-ZNF) proteins, which function as transcriptional repressors. One particular subfamily of KRAB-ZNF genes, including ZNF91, has expanded specifically in primates to comprise more than 110 loci in the human genome. Genes of the ZNF91 subfamily reside in large gene clusters near centromeric regions of human chromosomes 19 and 7 with smaller clusters or isolated copies in other locations. Phylogenetic analysis indicates that many of these genes arose before the split between the New and Old World monkeys, but the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. Paralogous loci are distinguished by divergence within their zinc finger arrays, indicating selection for proteins with different regulatory targets. In addition, many loci produce multiple alternatively spliced transcripts encoding proteins that may serve separate and perhaps even opposing regulatory roles because of the modular motif structure of KRAB-ZNF genes. The tissue-specific expression patterns and rapid structural divergence of ZNF91 subfamily genes suggest a role in determining gene expression differences between species and the evolution of novel primate traits.

Animals↗

PubMed1969

beta-Alanine as an Ethylene Precursor. Investigations Towards Preparation, and Properties, of a Soluble Enzyme System From a Subcellular Particulate Fraction of Bean Cotyledons.

A method is described for the preparation, from a subcellular particulate fraction of wax bean cotyledons, of a soluble enzyme system that is capable of converting beta-alanine to ethylene. In the presence of ATP, CoA, thiamine pyrophosphate, MgSO(4), and pyridoxal phosphate, ethylene production is maximum at a 0.5 mm concentration of beta-alanine. The system exhibits a pH optimum at 7.0 but when the pH is raised above 8, evolution of the volatile again increases and continues to do so up to pH 12. The enzyme system is stimulated by either NADPH or NADH; the concentration of NADPH necessary to obtain maximum activity is twice that of NADH. The requirement for a reducing agent is in agreement with the proposal that malonate semialdehyde, formed by an aminotransferase reaction from beta-alanine, is reduced to beta-hydroxypropionate. Both malonate semialdehyde and beta-hydroxypropionate are better stimulators of production of the volatile in the soluble system than is beta-alanine, and beta-hydroxypropionate is a better stimulator than malonate semialdehyde. This system is also able to incorporate tritium from tritiated water into ethylene; this supports the proposal that ethylene is formed by the decarboxylation of acrylate, the latter being formed from beta-hydroxypropionate.Experiments with both cold and labeled malonate suggest that this compound stimulates ethylene production by acting as an end product inhibitor that prevents the loss of malonate semialdehyde from the pathway. Malonate does not appear to serve as a precursor.Addition of cytoplasmic enzymes to the ;soluble system' (prepared from particulate enzymes) results in a considerable boost in ethylene production, but the specific activity (mmu1 / mg protein) is lowered from that of the particulate enzymes alone.

Journal Article↗

PubMed1994

Plasma concentrations of prolactin, noradrenaline, vasopressin and oxytocin during and after a prolonged epileptic seizure.

The time course and extent of changes in plasma prolactin, noradrenaline, vasopressin and oxytocin levels is reported following serial observations of a prolonged epileptic seizure arising in the temporal lobe, recorded by video-EEG-telemetry, in which the epileptic activity evolved from a simple partial to complex partial to secondarily generalised attack. The prolactin levels were markedly elevated during the phase of the simple partial seizure, at a time when consciousness was preserved, when motor activity was minimal and when EEG activity was highly localised. The hormonal levels continued to rise during the subsequent seizure evolution, suggesting that the duration (or intensity) of the seizure is an important, perhaps the most important, factor determining the degree of prolactin release during limbic seizures. Indeed, the prolactin elevation in this case (26 times the baseline level) is higher than any previously recorded, reflecting the unusual duration and intensity of this seizure. We did not observe the phenomenon of "exhaustion" of prolactin release and levels peaked after 49 min, and were high for over 2 h after the onset of the seizure, and after the convulsion had ceased. The concentrations of vasopressin, oxytocin and noradrenaline remained low during the aura, but rapidly increased during the phase of generalisation. The oxytocin and noradrenaline levels peaked during the phase of generalised convulsion, but the vasopressin levels peaked well into the post ictal phase, and remained high for several hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2026

The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection.

Beyond textbook functions in homeostatic metabolism, mitochondria are now recognized as central coordinators of cell-intrinsic and cell-extrinsic immune responses to infection. Directed trafficking of proteins and other molecules between mitochondria and the rest of the cell underlies a growing catalog of these activities. Some are pro-host; others are antagonized by viral effectors or co-opted by viruses entirely. How host and viral factors rewire the mitochondrial proteome during infection to shape these outcomes remains incompletely understood. The evolutionary history of this system adds another dimension: mitochondria retain biochemical signatures of their α-proteobacterial endosymbiotic origin, and ongoing co-evolution between viral, host, and mitochondrial genomes continues to shape the proteins that traffic to and from the organelle. Using published examples, we highlight general principles, mechanisms, and consequences of host and viral protein localization to and from the mitochondria. To support discovery, we present integrated gene lists identifying host mitochondrial factors with evidence for type I interferon stimulation, interactions with viral proteins, and signatures of positive selection. Together, these resources and the principles within offer a framework for understanding mitochondria not as passive metabolic machinery but as actively contested cellular territory whose protein composition is continuously negotiated between the host and the pathogen.

adaptation↗

PubMed1995

Trauma-related symptoms in veterans of Operation Desert Storm: a 2-year follow-up.

OBJECTIVE: This study was a 2-year follow-up in an ongoing prospective examination of development of trauma-related symptoms over time in a community group of veterans of Operation Desert Storm. METHOD: Sixty-two National Guard reservists, from one medical and one military police unit, completed the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and a DSM-III-R-based posttraumatic stress disorder (PTSD) symptom scale 1 month, 6 months, and 2 years after returning from the Middle East. Differences in symptom severity over time were analyzed by using repeated measure analyses of variance. RESULTS: Scores on the Mississippi scale, but not the DSM-III-R PTSD scale, increased significantly over time. Symptoms of hyperarousal were more severe at all time points than were symptoms of reexperiencing or avoidance. Level of combat exposure, as reflected by the Desert Storm trauma questionnaire, was significantly associated with the score on the Mississippi scale at 2 years but not at 1 month or 6 months. All subjects who met the Mississippi scale's diagnostic criteria for PTSD at 1 or 6 months still met the criteria at 2 years. CONCLUSIONS: Although symptoms were relatively mild, there was an overall increase in PTSD symptoms over 2 years. The statistical relationship between level of combat exposure and PTSD symptoms at 2 years, and not before, suggests that it may take time for the consequences of traumatic exposure to become apparent. Moreover, degree of exposure may be important in predicting the eventual development of symptoms. Continued follow-up will address the evolution of PTSD symptoms in Gulf War veterans.

Female↗

PubMedDate not supplied

Recent advances: ambulatory care and family medicine.

Recent advances in primary care have been and continue to be exciting and innovative. The evolution of pharmaceutical care has the potential to have an immediate impact in the primary care arena. A major focus of primary care research will center on the evaluation of pharmaceutical care and the consequences of implementing pharmaceutical care, such as reimbursement for clinical services, quality of life, and improved clinical outcomes. With an increasing emphasis being placed on the provision of health care through primary care providers, advances in primary care/family medicine pharmacotherapy promise to remain exciting and innovative.

Ambulatory Care↗

PubMed2005

Pathobiology of lymphoid and myeloid blast crisis and management issues.

Despite recent improvements in the treatment of early-stage disease, the blastic phase of chronic myeloid leukemia (CML) remains a therapeutic challenge. For imatinib-naïve patients, imatinib provided encouraging hematologic and cytogenetic benefits; however, the vast majority of CML blast crisis cases today arise in patients already on imatinib-based therapy. Clonal evolution and duplication of the Philadelphia chromosome continue to be associated with blastic phase transformation, but recent studies have identified BCR/ABL kinase domain mutations in 30%-40% of blast crisis patients. This implies that BCR-ABL-targeted therapy might have influenced the molecular road map to blastic transformation. In this review, we will examine the effect of imatinib on primitive CML progenitors and how this might influence the pathophysiology of blast crisis. A rational framework for deciding how best to integrate stem cell transplantation, traditional chemotherapy, imatinib, and other BCR-ABL kinase inhibitors in the care of blast crisis patients will also be discussed.

Algorithms↗

PubMed2000

The "presyrinx" state: is there a reversible myelopathic condition that may precede syringomyelia?

OBJECT: Alteration of cerebrospinal fluid (CSF) flow has been proposed as an important mechanism leading to the development of syringomyelia. We hypothesize that a "presyrinx" condition due to potentially reversible alteration in normal CSF flow exists and that its appearance may be due to variations in the competence of the central canal of the spinal cord. METHODS: Five patients with clinical evidence of myelopathy, no history of spinal cord trauma, enlargement of the cervical spinal cord with T1 and T2 prolongation but no cavitation, evidence for altered or obstructed CSF flow, and no evidence of intramedullary tumor or a spinal vascular event underwent MR imaging before and after intervention that alleviated obstruction to CSF flow. RESULTS: Preoperatively, all patients demonstrated enlarged spinal cords and parenchymal T1 and T2 prolongation without cavitation. Results of magnetic resonance (MR) imaging examinations following intervention in all patients showed resolution of cord enlargement and normalization or improvement of cord signal abnormalities. In one patient with severe arachnoid adhesions who initially improved following decompression, late evolution into syringomyelia occurred in association with continued CSF obstruction. CONCLUSION: Nontraumatic obstruction of the CSF pathways in the spine may result in spinal cord parenchymal T2 prolongation that is reversible following restoration of patency of CSF pathways. We refer to this MR appearance as the "presyrinx" state and stress the importance of timely intervention to limit progression to syringomyelia.

Adult↗

PubMed2002

Prospects for generating new antibiotics.

A plethora of human pathogens are now resistant to all clinically significant antibiotics causing a crisis, in the treatment and management of infectious diseases, but also presenting a clear danger to future public health. If drug resistance is going to be tackled successfully, new antibiotics must be continually developed to counteract the processes of evolution and natural selection in these populations of pathogens. Despite the introduction of powerful new technologies such as high throughput screening platforms and combinatorial chemistry, natural products still offer structural diversity worthy of screening for biological activity. Functional genomics can revolutionise rational drug design providing new targets for antimicrobial drug discovery. The clusters of genes, encoding enzymes that form bio-synthetic pathways leading to the synthesis of many natural products including polyketides and non-ribosomal peptides, are amenable to modern genetic engineering. Repositioning, deleting and replacing genes in these biosynthetic clusters has resulted in the synthesis of many 'un-natural' natural products. This review examines the engineering of proteins involved in chain initiation on polyketide synthases culminating in the production at high yield of a biologically active erythromycin derivative.

Drug Resistance, Microbial↗

PubMed1998

Measurement of autolysis in submerged batch cultures of Penicillium chrysogenum.

The process of cellular autolysis was studied in an industrial strain of Penicillium chrysogenum by a range of methods, including assessment of biomass decline, NH+4 release, changes in culture apparent viscosity, and by means of a quantitative assessment of changes in micromorphology using a computerized image analysis system. The pattern of total intracellular proteolytic and beta-1, 3-glucanolytic activity in the culture was also examined. The overall aim was to identify a suitable method, or methods, for examining the extent of autolysis in fungal cultures. Autolysis was studied in submerged batch processes, where DOT was maintained above 40% saturation (non-O2-limited), and, under O2-limited conditions. Both N and O2 limitation promoted extensive culture autolysis. Image analysis techniques were perhaps the most sensitive method of assessing the progress of autolysis in the culture. Autolytic regions within some hyphae were apparent even during growth phase, but became much more widespread as the process proceeded. The early stages of autolysis involved continued energy source consumption, increased carbon dioxide evolution rate, degradation of penicillin, and decreased broth filterability. Later stages involved widespread mycelial fragmentation, with some regrowth (cryptic growth) occurring in non-O2-limited cultures. Intracellular proteolytic activity showed two peaks, one during the growth phase, and the other during autolysis. Autolysis was also associated with a distinct peak in beta-1,3-glucanolytic activity, indicating that degradation of cell wall matrix polymers may be occurring during autolysis in this strain of P. chrysogenum.

Biomass↗

PubMed1985

Consumer behavior and the medical tradition.

The health care system is in a period of transition, and as competition intensifies, health care providers will be fighting for their share of the marketplace. In the current era of consumerism, with patients taking an active role in demanding more convenient, expedient, accommodating, and satisfying medical services, only those health care providers who can deliver this product will continue to prosper. This article traces the evolution of the health care market and how the changes will affect the patient.

Community Participation↗

PubMed1984

Hospital social work: cui bono?

The role of hospital social work departments (SWDs) is often the subject of dispute. Medical administrators, who hold the purse and policy strings, and heads of SWDs will have a major influence on the evolution of these departments in times of continued financial constraint. Their views on the importance of the services provided by the SWD, both currently and in the future, were canvassed by mailing a questionnaire to all teaching hospitals in Australia. A 90% overall response was achieved. In general, instrumental tasks (those associated with the traditional "almoner" role) were perceived by medical administrators and heads of SWDs as of equal importance. Independent professional social work activities and social change agent services were more highly valued by heads of SWDs. Most services were expected to increase, with only "placement" declining in the future. More change was expected by heads of SWDs than by medical administrators. These results are seen to reflect the differing values of the two groups, the significance of which is discussed.

Analysis of Variance↗

PubMed2000

Phylogenetic analysis of retroposon family as exemplified on human chromosome 13: further evidence for recent proliferation.

The retroposon SINE-R.C2 was first identified as a human-specific insertion in the complement C2 gene. In our previous study, SINE-R type retroposons, derived from the endogenous retrovirus HERV-K family, have been found to be hominoid specific. In this report on human chromosome 13, we identified eighteen new SINE-R retroposons resembling those we have previously reported on the sex chromosomes and on chromosomes 7 and 17. Phylogenetic analysis using the neighbor-joining method revealed that four SINE-R retroposons (13-16, 21, 23, 25) on chromosome 13 were closely related to the human-specific retroposon SINE-R.C2, with a high degree of sequence homology (95-97%). Such elements differ from the HERV-K10. LTR sequence from which they are derived in being deleted for the promoter region. Therefore while the evidence adds to the case that some classes of SINE-R element have continued to proliferate in hominid and hominoid evolution and may, as in the case of Fukuyama type muscular dystrophy, be a cause of insertional mutagenesis, they are less likely than the HERV-K10 LTR to have a positive effect on host gene activity.

Chromosomes, Human, Pair 13↗

PubMed2000

Clinical epidemiology and research on HIV infection in Switzerland: the Swiss HIV Cohort Study 1988-2000.

BACKGROUND AND OBJECTIVES: The Swiss HIV Cohort Study (SHCS) was initiated in 1988 and represented the main scientific component of the comprehensive response to the AIDS epidemic in Switzerland. It brought together physicians and scientists from five university hospitals (Basel, Berne, Geneva, Lausanne and Zurich) and two Cantonal hospitals (Lugano and St. Gallen). The objective of SHCS was, and still is, to produce rapid, high quality patient-oriented medical research in the field of HIV infection. METHODS: SHCS is a prospective population-based cohort study. Any HIV-infected person aged > or = 16 years is eligible to participate. Data collection and study procedures are standardised. Data quality and protocol monitoring are conducted at the coordination and data centre in Lausanne. Detailed information on demographics, income, mode of HIV acquisition, risk behaviours, clinical events, laboratory results, treatment and treatment tolerance is collected at registration and at 6-monthly intervals. RESULTS: Since 1996, 10,600 persons have been enrolled and the SHCS study population is considered fairly representative of the HIV-infected population in Switzerland, at least in terms of gender and mode of HIV acquisition. In 1999, 4600 patients were actively followed up and more than 70% of patients were receiving highly active antiretroviral therapy (HAART). As a consequence, mortality and the incidence of HIV-related opportunistic infections have decreased significantly in the recent past. Between 1996 and 2000, 91 original manuscripts have been published by SHCS scientists and physicians, almost exclusively in peer-reviewed journals. A wide range of scientific questions have been addressed, including HIV primary infection, the natural history of HIV infection, the clinical and biological impact of HAART, drug resistance, risk factors for disease evolution including the timing of treatment initiation, the role of CD4 receptors, the validity of HIV surveillance reports, determinants of treatment access and tolerance, clinical trials of new drug combinations, the interruption of prophylaxis following a favourable response to HAART and issues relating to quality of life and interaction between income, social level and disease evolution. CONCLUSION: The SHCS has had, and continues to have, a significant impact on medical practice, public health and research in Switzerland and beyond. It represents a network of excellence which has brought together and fostered intensive collaboration between physicians and institutions throughout this country and beyond. This was possible thanks to the support of the Federal Office of Public Health and the commitment of primary care physicians, researchers and patients. This project may be model for focused and prioritised multicentre and transdisciplinary research programmes.

AIDS-Related Opportunistic Infections↗

PubMed2002

[Radio-chemotherapy combinations in non operable localized non small cell lung carcinoma: updates and perspectives].

Optimal treatment of non operable localized non small cell lung carcinoma (NSCLC) continues to evolve. Increasing overall survival must evolute through improving local tumoral control and eradication of probable occult metastasis. Historically, median survival varies between 7 and 10 months with a standard conventional fractionated radiotherapy (RT). Induction chemotherapy (CT) followed by RT has demonstrated its superiority over RT alone, modality which is widely utilised. Other studies revealed best results with decreasing metastatic relapses. Three independent meta-analysis confirmed benefit obtained with cisplatin based CT followed by RT that allowed to consider this association as a gold standard. Other authors demonstrated an improvement of local control and survival with concomitant RT-CT or hyperfractionated accelerated RT. Results of all of these new therapeutic modalities still poor. Implication of new CT drugs has conducted for an emergence of new studies finding to demonstrate more encouraging results. Randomized trials are conducted in this way.

Antineoplastic Agents↗