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Biomedical subjects

A Thomas

Publications and source records attributed to A Thomas.

At least 217 records · Page 12Linked to original sources
PubMed1998

Suppression of the p300-dependent mdm2 negative-feedback loop induces the p53 apoptotic function.

The p53 tumor suppressor gene product interacts with the p300 transcriptional coactivator that regulates the transactivation of p53-inducible genes. The adenovirus E1A protein has been shown to bind to p300 and inhibit its function. E1A inhibits p53 transactivation and also promotes p53 accumulation by a p300-dependent mechanism. Murine double minute 2 (Mdm2) is a transcriptional target of p53 that binds to p53 and inhibits its transcriptional activity. E1A inhibited mdm2 transactivation without affecting the expression of p21(WAF1) or Bax, which resulted in high levels of p53 accumulation and apoptosis. Ectopic expression of p300 restored Mdm2 levels and inhibited p53-dependent apoptosis, as did ectopic expression of Mdm2. Thus, p300 is required for mdm2 induction by p53 and the subsequent inhibition of p53 stabilization. Inhibition of p300 by E1A results in stabilization of p53 and causes apoptosis. Moreover, E1B 19K or Bcl-2 expression in E1A-transformed cells abrogated p53-dependent apoptosis by restoring mdm2 transactivation by p53. Hence, p300 regulation of mdm2 expression controls apoptotic activity of p53, and 19K or Bcl-2 bypass E1A inhibition of p300 transactivation of Mdm2.

Adenovirus E1B Proteins↗
PubMed1998

Multi-plasmid DNA vaccination avoids antigenic competition and enhances immunogenicity of a poorly immunogenic plasmid.

DNA immunization is a very promising approach to the formulation of multivalent vaccines. However, little information is currently available on the immunogenicity of multi-plasmid formulations. To address this issue, we immunized mice with a combination of four plasmids encoding malarial antigens and we compared antibody responses with those obtained with single-plasmid injections. We found that when four plasmids encoding Plasmodium falciparum circumsporozoite protein, thrombospondin-related anonymous protein, major merozoite surface protein (MSP)1 and Pfs25 are co-injected into mice, Ab responses against each antigen are elicited at levels at least as high as the level obtained with single-plasmid injection. The quality of antibody production, as determined by isotype analysis, was similar when single- and multi-plasmid administrations were compared, indicating the priming of the same cytokine profile for CD4+ T helper cells. The sera from mice immunized with the four-plasmid formulation specifically recognized sporozoites, blood stage schizonts and gametes, indicating that DNA immunization induced antibody responses relevant to the native conformation. Finally and of particular interest, in the case of MSP1, the antibody response appears to be strongly potentiated by the presence of additional plasmids, indicating an adjuvant effect of DNA.

Animals↗
PubMed1998

[Reduced muscular oxygen tension and nerve impulse transmission from antishock hose. Reduction of oxygen tension in the tibial muscle and impulse transmission in the peroneal nerve from pneumatic -1 pressure from antishock hose].

OBJECT OF THE STUDY: The aim of the study was to assess, whether the pneumatic pressure of an antishock-trouser (AST) of 20-40 mm Hg induces a decreased oxygenation of the anterior tibial muscle and attenuates muscular response potential (MRP) of n. peronaeus profundus? METHODS: Among 22 normotensive, healthy volunteers the AST were tested by applying pressure values between 0 and 100 mm Hg and measuring the intracompartmental pressure, the muscular oxygen pressure as well as the MRP by electroneurographic means within a period of 6 hours. RESULTS: The median initial intracompartmental pressure value of the m. tibialis anterior was 12.0 mm Hg (Q25%/Q75%: 8.9/17.3), the muscular oxygen pressure 14.8 mm Hg (Q25%/Q75%: 11.5/22.0). Transmission of the pneumatic AST-leg segment pressure to the muscle: 97.7% (Q25%/Q75%: 89.2/99.8). Already in the low AST pressure field (20-40 mm Hg) a severe hypoxia occurred in one case. A reduction of MRP was noticed at an AST pressure rate of 10 mm Hg. In 5 of 6 cases AST pressure values of 60 mm Hg led to pathological pO2-values within 5-20 minutes. Almost without exception AST-pressure rates < 60 mm Hg resulted in an anoxia of the muscle and loss of the MRP. CONCLUSIONS: We should demand that the AST are only applied with models where the pressure generated within the single segments can be controlled by pressure gauge. The application of the AST seems to be justified for polytraumatised in severe haemorrhagic shock where the risk of a local tissue ischemia with systemical consequences must deliberately be accepted.

Adult↗
PubMed1998

Concentrations of leptin in the serum of pregnant, lactating, and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue.

Leptin concentrations were measured in the serum of cycling, pregnant, and lactating Sprague-Dawley rats. Serum leptin concentrations did not vary significantly during the estrous cycle. In contrast, as gestation advanced, serum leptin concentrations increased significantly, p < 0.0001. Following delivery, leptin concentrations declined and remained stable during lactation. Leptin messenger ribonucleic acid (mRNA) was identified in the visceral adipose tissue and placenta of rats sacrificed on days 14 and 21 of pregnancy. The relative abundance of placental leptin mRNA increased approximately 4 to 5 fold from day 14 to 21 of gestation. The pattern of elevated leptin concentrations in the serum of late pregnant rats is similar to that reported in pregnant women, therefore the rat may be a useful model for the study of leptin during pregnancy. The increase in leptin in the serum of late pregnant rats, as well as an increase in placental mRNA, raises the possibility that leptin may serve a physiological role for the late parturient rat and/or its young.

Abdomen↗
PubMed1998

Flow cytometric assessment of three different methods for the measurement of in vitro apoptosis.

Chlorambucil-induced apoptosis was assessed by three different flow cytometric methods in B-cell chronic lymphocytic leukaemia (B-CLL) cells cultured in vitro and the results were compared with those derived from the morphological assessment of the same samples. Spontaneous apoptosis was consistently observed in the control cultures in the absence of drug but this accounted for less than 12% of all cells in every case. The methods under investigation were the Annexin V labelling assay, the terminal deoxynucleotidyl transferase (TdT) end-labelling assay and the labelling of a 38 kDa mitochondrial membrane protein (7A6 antigen) which is exposed on cells undergoing apoptotic cell death (Apo2.7 assay). The Annexin V assay consistently stained a higher percentage of cells and with a greater separation between the positive and negative cell populations. We conclude that the phosphatidyl serine translocation to the outer leaflet of the cell membrane following an apoptotic signal, as labelled by Annexin V, probably occurs before the development of the DNA strand breaks or the exposure of 7A6 antigen in those cells triggered to die by apoptosis.

Annexin A5↗
PubMed1998

A prospective population-based cohort study of the effects of disablement and social milieu on the onset and maintenance of late-life depression. The Gospel Oak Project VII.

BACKGROUND: Population-based studies suggest substantial co-morbidity between physical illness and depression in late-life. However, a causal relationship has not been established. If a relationship exists, it is important to establish which aspects of poor health determine risk for depression, and which factors confer vulnerability or resilience in the face of poor health. We investigate the role of disablement, measured as impairment, disability and handicap. METHODS: A prospective population-based cohort study, comprising an index assessment and 1 year follow-up, of all residents aged 65 years or over, of an electoral ward in London, UK (N = 889). RESULTS: The prevalence of SHORT-CARE pervasive depression was 17.7% at index assessment. The 1 year onset rate for pervasive depression was 12.0%, and the 1 year maintenance rate 63.2%. There was a high mortality rate among the depressed. Disablement, particularly handicap was the most important predictor of the onset of depression (population attributable fraction, 0.69). Lack of contact with friends was a direct risk factor but also modified the association between handicap and depression. Marriage was protective for men, but a risk factor for women. Maintenance of depression was predicted by low levels of social support and social participation, rather than by disablement. CONCLUSIONS: It seems likely that disablement, specifically handicap, is the chief cause of onsets of depression in late-life. Genetic predisposition, early adversity and serious life events may play a less prominent role than in earlier life. Effective prevention of late-life depression requires attention at the structural level to the sources of handicap within communities.

Activities of Daily Living↗
PubMed1998

Cultural barriers in oncology: issues in obtaining medical informed consent from Japanese-American elders in Hawaii.

In east-west cultural contexts medical decision-making by elderly Japanese-American oncology patients is made complex by cultural differences from mainstream service providers. Cultural, religious and practical factors thought to contribute to delays in obtaining informed consent for treatment in oncology from mentally competent Japanese-American elders in Hawai'i are identified in this study of health care professionals at Queen's Medical Center in Honolulu (n = 50). Circumstances under which Japanese-American elders sign informed consent documents without understanding them are also examined. Recommendations are offered by the participants and researchers for improvements to the informed consent process. Implications of the findings and recommendations are discussed for Health Care Practice with Japanese-American and other ethnic elderly patients in mainstream health care organizations.

Journal Article↗
PubMed1998

Constant rate infusion of vancomycin in premature neonates: a new dosage schedule.

AIMS: Since vancomycin's bactericidal action has been shown to be time-dependent, a constant rate infusion over 24 h might result in a better bactericidal efficacy. The purpose of this study was to define a new dosage schedule in prematures. METHODS: Two vancomycin 24 h constant rate infusion schedules were tested in two groups of neonates. Postconceptional age (PCA) was 27 to 41 weeks in group 1 (n=24) and 28 to 51.5 weeks in group 2 (n=29). Group 1 neonates received continuous infusion of 10 to 30 mgkg(-1) day(-1), adjusted for PCA and weight. Group 2 was designed to take into account the significant relationship observed in group 1 between vancomycin clearance standardized on weight and PCA and consisted of a constant loading dose of 7 mg kg(-1) followed by continuous infusion of 10 to 40 mg kg(-1) day(-1) adjusted for PCA and weight. RESULTS: Mean vancomycin serum concentration at steady state was 11+/-3.1 mg1(-1) in group 1 and 15.4+/-6.2 mg1(-1) in group 2. Fifty-six percent of group 1 values vs 88% of group 2 values were between 10 and 30 mg at steady state (P<0.01). Both regimens were well tolerated. CONCLUSIONS: A loading dose of vancomycin followed by constant rate infusion of the appropriate dose adjusted for PCA and weight might improve vancomycin concentrations in neonates.

Anti-Bacterial Agents↗
PubMed1998

Stationary organotypic cultures of oxytocin and vasopressin magnocellular neurones from rat and mouse hypothalamus.

Rat and mouse hypothalami from postnatal animals containing highly differentiated neurones survive very well in long-term (>15 days in vitro, DIV) stationary organotypic cultures. Magnocellular oxytocin (OT) and vasopressin (VP) neurones are present in identifiable paraventricular (PVN), supraoptic (SON) and accessory (ACC) nuclei in these cultures. After 15 DIV in standard medium immunocytochemistry revealed 427 +/- 63 OT cells and 217 +/- 27 VP cells per cultured rat hypothalamus, and 380 +/- 72 OT cells and 622 +/- 91 VP cells per cultured mouse hypothalamus. Following a 7-day adaptation period in standard culture medium containing serum, the rat slice-explants survived very well after subsequent transfer to defined, serum- free media (SFM) for an additional 8 days. The number of OT cells surviving in SFM was 612 +/- 147 OT cells per cultured rat hypothalamus. Only 0.5% of the magnocellular OT and VP neurones in the cultures appeared to express both peptides. Experiments on c-fos gene expression in these cultures showed that while only 12% of the magnocellular OT and VP neurones contained barely detectable Fos protein in their nuclei under control conditions, potassium depolarization of these cultures for 3 h produced intense c-fos expression in 87-91% of these cells. Thus, magnocellular neurones in these cultures are sufficiently stable and responsive to permit long-term physiological and gene expression studies to be done under defined media conditions.

Animals↗
PubMed1998

Use of stroke distance in the early detection of simulated blood loss.

OBJECTIVES: To compare the effects of simulated and mild actual hemorrhage on parameters used traditionally to assess hemorrhaging patients: heart rate (HR), blood pressure (BP), and Shock Index (SI = HR/systolic BP), with stroke distance (SD) measured ultrasonically as an index of cardiac stroke volume. MATERIALS AND METHODS: Hemorrhage was simulated in 19 healthy volunteers by the application of graded lower-body negative pressure (LBNP) (0, -20, -40, and -60 mm Hg) to pool blood in the lower body and reduce venous return. Measurements were also made before and after a standard blood donation (450 mL) in nine healthy volunteers. MEASUREMENTS AND MAIN RESULTS: SD decreased significantly and progressively from the baseline level of 23.8+/-5.7 cm (mean+/-SD) at each level of LBNP: by 3.4+/-1.9, 7.4+/-2.5, and 11.8+/-3.2 cm at LBNP of -20, -40, and -60 mm Hg, respectively. Neither HR nor SI changed significantly at the lowest level of LBNP (-20 mm Hg), but they showed progressive, significant increases thereafter. Mean BP did not change significantly at any level of LBNP. Similarly, after a controlled hemorrhage of 450 mL, SD decreased significantly by 3.3+/-1.6 cm from 22.2+/-2.8 cm, whereas HR and SI remained unchanged and mean BP increased slightly. CONCLUSION: Changes in SD may provide an earlier indication of progressive blood loss than either HR or BP alone or in combination.

Adult↗
PubMed1998

Retrospective analysis of the effects of psychotherapeutic interventions on outcomes of psychogenic nonepileptic seizures.

PURPOSE: Uncertainty exists regarding the effectiveness of psychotherapy in patients with psychogenic nonepileptic seizures (PNES). We retrospectively reviewed the outcomes of therapeutic interventions in a cohort of patients with PNES. METHODS: We identified patients with PNES by outpatient video-EEG (VEEG) between 1992 and 1996. We retrospectively analyzed the effects on outcomes of various types of interventions for PNES administered at random, using a structured interview and review of medical records. Patients with subjective events and severe psychosis were excluded. Patients who required inpatient monitoring because the outpatient VEEG was inconclusive were also excluded. RESULTS: One hundred patients were diagnosed with PNES between 1992 and 1996: 61 patients completed the study. The average age was 43.3 years, and 90% were female. Nine (15%) had had PNES <1 year, and 7 (11%) had epilepsy. Eleven of 16 patients (68%) who received five or more counseling sessions, including showing the videotaped recording of the nonepileptic spell (13 of 16) by the comprehensive epilepsy program (CEP) psychotherapist had cessation (7 of 16) or reduction (4 of 16) of their episodes. Eleven of 15 patients (73%) who received only the feedback and care of their CEP neurologists had similar favorable outcome. Twelve of 25 patients (48%) who received counseling by a non-CEP psychotherapist or psychiatrist had cessation (10 of 25) or reduction (2 of 25) of episodes. Five patients who received no feedback or intervention had no improvement (4 of 5) or worsening (1 of 5) of the PNES. CONCLUSIONS: Psychotherapy or feedback provided by CEP professionals with experience in epilepsy and PNES improves outcome and may be superior to other or no interventions.

Adult↗