Model of Morphogenesis with Repelling Signaling.

The paper is devoted to a conceptual model of cell patterning, based on a generalized notion of the epigenetic code of a cell determining its state. We introduce the concept of signaling depending both upon the spatial distance between cells and the distance between their cell states (s-distance); signaling can repel cells in the space of cell states (s-space) or attract them. The influence of different types of repelling signaling on the evolution of cells is considered. Stabilizing signaling, namely a signaling monotonically decreasing with s-distance, causes the restoring of cell states after perturbations; destabilizing signaling, i.e., the one in which the signaling monotonically increases with s-distance, causes the appearance of pairs of cells with alternating cell states (one close to the state conventionally called "head", and another close to the "tail" state). Non-monotonic (in s-space) signaling splits the cells into groups. The model shows that different types of signaling may provide different types of cellular patterns. General principles for applying this model to complex cellular structures are discussed.

The effect of reduced myocardial cyclic AMP content on the response to milrinone in the isolated guinea pig heart.

BACKGROUND: Cardiac beta receptor down-regulation is associated with a reduction of tissue cyclic adenosine monophosphate (AMP) content. Milrinone exerts its effects by inhibiting the metabolism of existing cyclic AMP. The purpose of this study was to evaluate the effect of reduced myocardial cyclic AMP content on the pharmacologic action of milrinone. METHODS: A reduction of myocardial cyclic AMP content was produced by creating catecholamine depletion in the hearts of adult guinea pigs with intraperitoneal reserpine. Control animals received the reserpine vehicle. Isolated heart perfusion was maintained with modified Krebs buffer, and hearts were paced at 270 beats/min. A latex balloon and transducer-tipped catheter were inserted into the left ventricle. Isovolemic work was maintained at a constant balloon volume. Hearts from control and reserpine treated animals were perfused for 20 minutes with buffer containing either no milrinone, 1.7 x 10(-6), or 1.0 x 10(-4) mol/L milrinone (n = 12 for each dose). Maximal positive and negative dP/dt were assessed. The hearts were then frozen and cyclic AMP was measured. RESULTS: Cyclic AMP content was significantly lower in the reserpine-treated hearts at each milrinone concentration (0.33 +/- 0.01 vs 0.46 +/- 0.01; 0.33 +/- 0.01 vs 0.53 +/- 0.01; 0.30 +/- 0.01 vs 0.61 +/- 0.02 pmol/mg wet weight, p < 0.05). Milrinone significantly increased positive and negative dP/dtmax (p < 0.05), but no difference was observed between control and reserpine-treated hearts. CONCLUSIONS: Endogenous catecholamine depletion reduces myocardial cyclic AMP content but does not attenuate the response to milrinone in the isolated heart.

Isolated four-chamber working swine heart model.

BACKGROUND: Isolated heart models separate cardiac characteristics from systemic characteristics with subsequent findings used in cardiac research, including responses to pharmacologic, mechanical, and electrical components. The model objective was to develop the ability to represent in situ physiologic cardiac function ex vivo. METHODS: Swine hearts were chosen over rat or guinea pig models due to their notably greater anatomical and physiologic similarities to humans. An in vitro apparatus was designed to work all four chambers under simulated in situ physiologic conditions. Using standard cardiac surgical techniques, 12 porcine hearts (mean weight 331 +/- 18 g) were explanted into the apparatus. Preload and afterload resistances simulated in situ input and output physiologic conditions. Hemodynamic characterizations, including cardiac output, max +/- dP/dt, and heart rate, were used to determine in situ function leading to explantation (prethoracic operation, postmedial sternotomy, and postperidectomy) and during in vitro function (t = 0, 60, 120, and 240 minutes). RESULTS: In vitro performance decayed with time, with statistical differences from base line (t = 0) function at t = 240 minutes (p > 0.05). CONCLUSIONS: An isolation and in vitro explantation protocol has been improved to aid in the study of isolated cardiac responses, and to determine cardiac hemodynamic function during open chest operation, transplantation, and in vitro reanimation with a crystalloid perfusate. The resulting model offers similar working physiologic function, with real-time imaging capabilities. The resulting model is advantageous in representing human cardiac function with regard to anatomic and physiologic functions, and can account for atrial and ventricular interactions.

Additional self-monitoring tools in the dietary modification component of The Women's Health Initiative.

Self-monitoring promotes behavior changes by promoting awareness of eating habits and creates self-efficacy. It is an important component of the Women's Health Initiative dietary intervention. During the first year of intervention, 74% of the total sample of 19,542 dietary intervention participants self-monitored. As the study progressed the self-monitoring rate declined to 59% by spring 2000. Participants were challenged by inability to accurately estimate fat content of restaurant foods and the inconvenience of carrying bulky self-monitoring tools. In 1996, a Self-Monitoring Working Group was organized to develop additional self-monitoring options that were responsive to participant needs. This article describes the original and additional self-monitoring tools and trends in tool use over time. Original tools were the Food Diary and Fat Scan. Additional tools include the Keeping Track of Goals, Quick Scan, Picture Tracker, and Eating Pattern Changes instruments. The additional tools were used by the majority of participants (5,353 of 10,260 or 52% of participants who were self-monitoring) by spring 2000. Developing self-monitoring tools that are responsive to participant needs increases the likelihood that self-monitoring can enhance dietary reporting adherence, especially in long-term clinical trials.

Experimental trichinellosis in horses: biological and parasitological evaluation.

Three groups of three horses each were, respectively, infected with 5000, 20,000 and 50,000 larvae of Trichinella spiralis. The strain used was isolated from a human biopsy during horsemeat-related outbreaks of trichinellosis in France. Transient muscular disorders were only observed in two of the horses infected with 50,000 larvae but none of the horses had fever. A significant increase in blood eosinophils was noticed in 5 horses. Serum LDH, aldolase and CPK peaked at the fifth week post-infection. Specific IgG assayed by indirect immunofluorescence and ELISA, appeared 2-5 weeks post-infection and disappeared between 16 and 40 weeks. The distribution of T. spiralis larvae was maximal in the tongue, masseters and diaphragm, but a large decrease in the number of larvae recovered from the muscles was noticed among the horses slaughtered at the beginning and end of the experiment. In muscular histological sections, larvae were observed in an intramyofibrillar position and were surrounded by a mild to severe inflammatory reaction.

Comparison of four methods for early detection of experimental Trichinella spiralis infections in pigs.

Four methods employed in the diagnosis of experimental porcine trichinellosis (trichinoscopy, digestion method, immunofluorescence and enzyme linked immunosorbent assay (ELISA)) were compared by eleven laboratories in the countries of the European Economic Community and Sweden. The aim of this study was to test the reliability of ELISA during the onset of T. spiralis infection. Material from conventionally raised pigs infected with 1500 to 10000 larvae was compared to uninfected controls at Day 17 and Day 21 post infection. The serological techniques gave higher percentages of positive results than the direct techniques. Specific antibodies could be demonstrated with ELISA at an earlier stage and at higher percentages than with the other methods. ELISA micro-assay was the most sensitive procedure.

Outbreak of trichinellosis in the Midi-Pyrénées region of France January - March 1998.

Two outbreaks of trichinellosis in the Tarn et Garonne, département, France were reported by the departmental health autorities on 2 March 1998, to the Réseau National de Santé Publique (RNSP). An epidemiological investigation began on 3 March in order to.

Outbreak of trichinellosis in the Midi-Pyrenees region of France January - March 1998.

Two outbreaks of trichinellosis in the Tarn et Garonne, departement, France were reported by the departmental health autorities on 2 March 1998, to the Reseau National de Sante Publique (RNSP). An epidemiological investigation began on 3 March in order to

[The dangers for public health connected to the consumption of horse meat]. / Les dangers pour la santé publique liés à la consommation de la viande de cheval.

After an outline of the ways in which horse meat is produced and consumed, the authors review specific and general risks associated with this product, and methods for the control and prevention of these risks are given. With regard to biological hazards transmitted by horse meat, the relevant zoonoses are considered, followed by a discussion of the two principal agents responsible for foodborne disease in human beings: Salmonella and Trichinella. Among chemical hazards, the toxic effects of cadmium are prominent. Although these hazards can be identified, the actual risks to human health are difficult to estimate, because of the paucity of scientific data.

Recent news on trichinellosis: another outbreak due to horsemeat consumption in France in 1993.

A new outbreak of trichinellosis occurred in France in December 1993 and involved around 550 patients. The authors report here how recent knowledge on Trichinella have been helpful to investigate this outbreak.

The Axis II group: treating severely characterologically disturbed patients.

Treating the chronically mentally ill involves not only working with patients suffering from schizophrenia and other prolonged or recurrent psychotic illnesses, it also means providing treatment for patients with severe personality disorders. Many of these patients are also active substance abusers. This article examines the therapeutic and management issues raised for outpatient clinicians who work with these patients. Consideration is devoted to the special problems in treating the dual diagnosis patient, issues of patient and therapist safety, limit setting, splitting dynamics, and countertransference reactions. A set of recommendations is offered for conducting outpatient group therapy, specifying what is needed from both the clinicians and the facility in which this type of treatment is provided.

A new necessary condition on interaction graphs for multistationarity.

We consider a dynamical system, described by a system of ordinary differential equations, and the associated interaction graphs, which are defined using the matrix of signs of the Jacobian matrix. After stating a few conjectures about the role of circuits in these graphs, we prove two new results relating them to the dynamic behaviour of the system: a sufficient condition for qualitative unstability, and a necessary condition for the existence of several stationary states. These results are illustrated by examples of regulatory modules in two variables, such as those occurring in biological networks.

The power in our hands: integrating developmental care into neonatal transport.

Research has shown that infants who receive developmentally supportive care during the course of medical treatment in the NICU have improved long-term developmental outcomes. Developmentally sound interventions should be implemented as early as possible in the hospital course and can be incorporated successfully into the care provided during transport of sick neonates. If developmental interventions are planned and implemented thoughtfully and consistently throughout the transport course, it may be possible to reduce or prevent neurodevelopmental complications.

Differentiation of Trichinella isolates by polymerase chain reaction.

Oligonucleotide primers were synthesized for the polymerase-chain-reaction amplification of target DNA from two sequences of Trichinella spiralis. Six strains belonging to T. spiralis, T. nativa, T. britovi, T. pseudospiralis, and T. nelsoni were tested. Amplification products were obtained with T. spiralis, T. britovi, and T. nelsoni DNA from a 53-kDa antigen cDNA sequence and with T. spiralis and T. nelsoni DNA from a 1.6-kb repetitive DNA sequence. Differences in the length of the amplification products obtained from the repetitive sequence would enable a differentiation between T. spiralis and T. nelsoni, suggesting that the 1.6 kb repetitive DNA sequence would not be specific for T. spiralis. No amplification was detected for T. nativa or T. pseudospiralis DNA from the two sequences and for T. britovi DNA from the 1.6-kb repetitive DNA sequence.

Expectations and high school change: teacher-researcher collaboration to prevent school failure.

Describes the multilevel outcomes of a collaborative preventive intervention for ninth-graders at risk for school failure using qualitative and quasi-experimental methods. Teachers, administrators, and researchers implemented innovative practices communicating positive expectations for low-achieving adolescents in their transition to high school. Changes were made in the practices of curriculum, grouping, evaluation, motivation, student responsibility, and relationships (in the classroom, with parents, and in the school). Both implementation and evaluation evolved as a function of collaboration. Change was promising but not uniform. Project teachers became more positive about students and colleagues, expanded their roles, and changed school tracking policies. The 158 project students, in contrast to the 154 comparison students showed improved grades and disciplinary referrals post-intervention and increased retention in school 1 year later, but their absences rose and improved performance was not maintained. The implications of this analysis for school-based interventions and its evaluation are discussed.

The UL45 gene product is required for herpes simplex virus type 1 glycoprotein B-induced fusion.

Herpes simplex virus type 1 (HSV-1) syncytial (syn) mutants cause formation of giant polykaryocytes and have been utilized to identify genes promoting or suppressing cell fusion. We previously described an HSV-1 recombinant, F1 (J.L. Goodman, M. L. Cook, F. Sederati, K. Izumi, and J. G. Stevens, J. Virol. 63:1153-1161, 1989), which has unique virulence properties and a syn mutation in the carboxy terminus of glycoprotein B (gB). We attempted to replace this single-base-pair syn mutation through cotransfection with a 379-bp PCR-generated fragment of wild-type gB. The nonsyncytial viruses isolated were shown by DNA sequencing not to have acquired the expected wild-type gB sequence. Instead, they had lost their cell-cell fusion properties because of alterations mapping to the UL45 gene. The mutant UL45 gene is one nonsyncytial derivative of F1, A4B, was found to have a deletion of a C at UL45 nucleotide 230, resulting in a predicted frame shift and termination at 92 rather than 172 amino acids. Northern (RNA) analysis showed that the mutant UL45 gene was normally transcribed. However, Western immunoblotting showed no detectable UL45 gene product from A4B or from another similarly isolated nonsyncytial F1 derivative, A61B, while another such virus, 1ACSS, expressed reduced amounts of UL45. When A4B was cotransfected with the wild-type UL45 gene, restoration of UL45 expression correlated with restoration of syncytium formation. Conversely, cloned DNA fragments containing the mutant A4B UL45 gene transferred the loss of cell-cell fusion to other gB syn mutants, rendering them UL45 negative and nonsyncytial. We conclude that normal UL45 expression is required to allow cell fusion induced by gB syn mutants and that the nonessential UL45 protein may play an important role as a mediator of fusion events during HSV-1 infection.