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Biomedical subjects

D Jolly

Publications and source records attributed to D Jolly.

At least 37 records · Page 2Linked to original sources
PubMed1998

A chimeric Ty3/Moloney murine leukemia virus integrase protein is active in vivo.

This report describes the results of experiments to determine whether chimeras between a retrovirus and portions of Ty3 are active in vivo. A chimera between Ty3 and a Neo(r)-marked Moloney murine leukemia virus (M-MuLV) was constructed. The C-terminal domain of M-MuLV integrase (IN) was replaced with the C-terminal domain of Ty3 IN. The chimeric retroviruses were expressed from an amphotrophic envelope packaging cell line. The virus generated was used to infect the human fibrosarcoma cell line HT1080, and cells in which integration had occurred were selected by G418 resistance. Three independently integrated viruses were rescued. In each case, the C-terminal Ty3 IN sequences were maintained and short direct repeats of the genomic DNA flanked the integration site. Sequence analysis of the genomic DNA flanking the insertion did not identify a tRNA gene; therefore, these integration events did not have Ty3 position specificity. This study showed that IN sequences from the yeast retrovirus-like element Ty3 can substitute for M-MuLV IN sequences in the C-terminal domain and contribute to IN function in vivo. It is also one of the first in vivo demonstrations of activity of a retrovirus encoding an integrase chimera. Studies of chimeras between IN species with distinctive integration patterns should complement previous work by expanding our understanding of the roles of nonconserved domains.

Animals↗
PubMed1998

Outcome of erosive/ulcerative reflux oesophagitis in 181 consecutive patients 5 years after diagnosis.

BACKGROUND: Controversy exists as to whether oesophagitis worsens over the long-run and long-term follow-up studies of homogeneous series are scarce. AIMS: This study assessed the level of symptoms and the proportions of patients who underwent anti reflux surgery or were on antisecretory therapy. PATIENTS AND METHODS: Files from 286 patients with a first time diagnosis were retrieved. Outcome data was obtained over the phone from the general practitioners and from the patients. RESULTS: Seventy-five patients had died (26.2%), 2 of whom from anti reflux surgery, and 30 (14.2%) could not be contacted. Of the 181 patients contacted, 18 (9.9%) had undergone anti reflux surgery. Of the 163 remaining patients, 57.7% were no longer on medication (group 1), 31.9% were using antacids, alginate or cisapride (group 2) and 10.4% were on antisecretory therapy (group 3). High initial grades of oesophagitis and older age were linked to antisecretory drug consumption. There were no new cases of haemorrhage or stricture. CONCLUSIONS: Patients in this study showed a low rate of symptomatic relapse and of antisecretory drug requirements and no complications despite having had oesophageal breaks.

Adolescent↗
PubMed1997

A Phase I clinical trial of immunotherapy with interferon-gamma gene-modified autologous melanoma cells: monitoring the humoral immune response.

BACKGROUND: Tumor cells transduced with cytokine genes provide immunogenic vaccines for cancer immunotherapy. METHODS: A Phase I clinical trial was conducted for the specific active immunization of melanoma patients with interferon-gamma (IFN-gamma) gene-modified autologous melanoma tumor cells. Short term melanoma cultures were transduced retrovirally with the gene for human IFN-gamma. The genetically modified melanoma cells secreted biologically active IFN-gamma and showed enhanced expression of major histocompatibility complex class I and class II surface antigens. These cells were inactivated by irradiation (50 gray) and were cryopreserved for the vaccine. Twenty melanoma patients were enrolled in this clinical trial. The immunizations were administered in escalating doses once every 2 weeks for 3 months. The first and second injections consisted of 2 million cells, followed by 6 million for the third and fourth injections, and then 18 million for the fifth and sixth injections. The humoral immune responses of the patients were assessed by enzyme-linked immunoadsorbent assay, radioimmunoassay, and radioimmunoprecipitation. RESULTS: Thirteen of the 20 patients completed the immunization protocol. Eight of these 13 patients showed a humoral immunoglobulin (Ig)G response against autologous and allogeneic melanoma cells. The other five patients either had no detectable antimelanoma antibodies or showed a weak IgG response that did not rise significantly above the preimmune level. All the sera contained low or undetectable levels of antimelanoma IgM antibodies. The IgG response increased progressively in titer during the course of immunization. The positive sera showed preferentially strong binding to melanoma cell lines and some cross-reactivity to nonmelanoma tumors. A 75-80 kD antigen on melanoma cells was immunoprecipitated by postimmune sera of 3 of the responding patients. Preimmune sera from these three patients and sera from other patients immunized with a standard nontransduced melanoma cell vaccine failed to precipitate this antigen. Two patients with significant increases in serum IgG had clinical tumor regression, and two additional patients with low serum IgG response had transient shrinkage of nodular disease during therapy. CONCLUSIONS: These data suggest that gene therapy with IFN-gamma-transduced melanoma cells is safe and worthy of further investigation in patients with less advanced stage malignant melanoma. The ability to monitor changes in the humoral responses of the immunized patients has been demonstrated.

Cancer Vaccines↗
PubMed1997

Effect of Low Glacial Atmospheric CO2 on Tropical African Montane Vegetation

Estimates of glacial-interglacial climate change in tropical Africa have varied widely. Results from a process-based vegetation model show how montane vegetation in East Africa shifts with changes in both carbon dioxide concentration and climate. For the last glacial maximum, the change in atmospheric carbon dioxide concentration alone could explain the observed replacement of tropical montane forest by a scrub biome. This result implies that estimates of the last glacial maximum tropical cooling based on tree- line shifts must be revised.

Journal Article↗
PubMed1997

Life events and disability in rheumatoid arthritis: a European cohort.

The objective was to study the relationship between life events (LE) and the clinical status of patients suffering from recently diagnosed rheumatoid arthritis (RA) in a 2 yr follow-up. As part of a multicentre European cohort study, 370 French and Dutch patients were questioned three times at 1 yr intervals about LE which had occurred in the previous year. Three criteria were used to quantify the degree of disease activity (Ritchie's index), the level of functional disability [Health Assessment Questionnaire (HAQ)] and perceived health [Overall Evaluation of Health (OEH)]. Total LE and desirable LE showed a weak negative correlation with the HAQ scores. On the other hand, death-related LE did not seem to modify patient status. The higher the number of health-associated LE, the greater the deterioration in HAQ and OEH scores. The results indicate that LE do not affect the course of early RA in a spectacular manner.

Adult↗
PubMed1997

[Transthoracic echocardiography and diagnosis of acute pulmonary embolism. Change in the diagnostic valve with respect to thresholds of classification].

The diagnostic value of transthoracic echocardiography in acute pulmonary embolism is not well established. Although many parameters are abnormal, the thresholds used vary according to the authors, limiting the contribution of the investigation to the diagnosis. In a prospective study of 70 patients with suspected acute pulmonary embolism without previous cardio-respiratory disease, the authors tried to determine the diagnostic thresholds using discriminating linear analysis and ROC curves. Parameters easily recorded in an emergency were analysed: end diastolic ventricular dimensions, ratio of these diameters and maximal velocity of tricuspid regurgitant flow. Thirty-one patients had pulmonary embolism quantified by the Miller index (average: 16 +/- 7, range 2 to 28). Measurements of left ventricular dimension were disappointing (sensitivity: 0.52, specificity: 0.73 for a threshold value of 45 mm). The right ventricular dimension was a better predictive parameter (sensitivity: 0.70, specificity: 0.86 for a threshold value of 25 mm). However, the ratio of right to left ventricular dimension had a better diagnostic value (sensitivity: 0.85, specificity: 0.78 for a threshold value of 0.5). The best diagnostic parameter was the maximal velocity of tricuspid regurgitation (sensitivity: 0.93, specificity: 0.82 for a threshold value of 2.5 m/s). The authors conclude that the maximal velocity of tricuspid regurgitation with a threshold of 2.5 m/s and the ratio of the ventricular dimensions with a threshold value of 0.5 are valuable diagnostic indicators for acute pulmonary embolism.

Acute Disease↗
PubMed1996

Interferon gamma (IFNgamma) gene transfer of an EMT6 tumor that is poorly responsive to IFNgamma stimulation: increase in tumor immunogenicity is accompanied by induction of a mouse class II transactivator and class II MHC.

Abstract Interferon gamma (IFNgamma) is an important cytokine with immunomodulatory properties that include activation of immune cells and induction of class I and class II major histocompatibility complex antigens. In this study a retroviral vector was used to introduce the IFNgamma gene into EMT6 tumor cells to assess the effect of IFNgamma gene expression on tumor immunogenicity. Transfectants were selected in G418-containing tissue-culture medium and were determined to express the inserted IFNgamma gene by reverse transcriptase/polymerase chain reaction. Flow-cytometric analysis revealed that parental unmodified EMT6 cells constitutively expressed only class I MHC and were poorly responsive to exogenous IFNgamma stimulation, whereas class II MHC was induced in IFNgamma-transfected cells. The induction of class II MHC in IFNgamma-transfected cells correlated with the expression of a mouse class II transactivator gene that was dormant in unmodified or mock-transfected cells. In addition, IFNgamma-gene-transfected tumor cells were found to secrete up to 17 ng IFN (equivalent to 75 units/10(6) cells) by enzyme-linked immunosorbent assay (ELISA). Whereas parental EMT6 cells grew unchecked, the growth of genetically modified tumor cells was significantly inhibited in immunocompetent mice. Rechallenge of animals that rejected an IFNgamma-transfected EMT6 clone (EMT6-B17) with parental EMT6 cells resulted in tumor rejection, suggesting that IFNgamma-transfected EMT6 cells were able to induce long-term immunity. Mixing experiments using gene-transfected and unmodified tumor cells demonstrated that 10% of IFNgamma-transfected cells in the population was sufficient to protect mice against subsequent challenge with tumorigenic EMT6 cells. These studies demonstrate that the immunogenicity of tumor cells that are poorly responsive to exogenous IFNgamma can be enhanced by inserting and expressing the IFNgamma transgene. These findings also suggest a role for class II MHC in reducing tumorigenicity of the EMT6 tumor and inducing long-term tumor immunity.

Animals↗
PubMed1996

In vivo microdialysis in the rat: low cost and low labor construction of a small diameter, removable, concentric-style microdialysis probe system.

A method for construction of a serviceable and low cost intracerebral microdialysis system is presented. The system includes a probe and its supporting components. The probe is of the concentric design. The supporting components are an implantable guide cannula, a tether, and a swivel. After minimal training, workers can make many probes of consistent performance characteristics in a short time. Because all of the parts are commercially produced, users may obtain custom-made components which are finished with factory precision and accuracy. The user may readily vary probe characteristics such as depth of implant and size of active portion, so that different types of dialysis may be performed in different brain regions. The available choices in tether and swivel configurations make this microdialysis system readily adaptable to diverse testing environments. Excluding labor and startup costs, the costs, the cost per probe is approximately $11.00 (US). Taken together, the system provides a flexible, low cost means for performing in vivo microdialysis in freely moving rats.

Animals↗
PubMed1996

Effectiveness and prognostic factors of success in 12 smoking cessation clinics in the hospitals of Assistance publique-Hôpitaux de Paris.

We evaluated whether the location of a smoking cessation clinic in a hospital enhances the success rate compared to that found in the literature, regardless of the type of treatment. We assessed the results and identified prognostic factors of success in 12 smoking cessation clinics situated in 12 hospitals of the Assistance publique-Hôpitaux de Paris (AP-HP). The clinics were included in the study after a call for participation. The response rate was 60%. The study design was prospective, multicentric and descriptive. The study lasted 9 months. Follow-up took place 3 and 6 months after the first visit. The definition of success was self-reported total abstinence from cigarette smoking during the month preceding the 6-month follow-up. Success rate was 27%, failures were 66%, and 7% were lost to follow-up. Prognostic factors of success were not related to the hospital setting. We conclude that for a number of structural reasons that we explain, according to this study, the location of smoking cessation clinics in hospitals does not enhance their success rate compared to that found in the literature.

Adult↗
PubMed1996

Use of transthoracic Doppler echocardiography combined with clinical and electrocardiographic data to predict acute pulmonary embolism.

Transthoracic echocardiography and continuous wave Doppler were prospectively performed in 132 out-patients with suspicion of pulmonary embolism, and who had no previous history of severe cardiac or pulmonary disease. Bedside echocardiography determined diagnosis other than pulmonary embolism in 55 patients. Further study was completed in 70 patients; pulmonary embolism was found in 31 and excluded in 39. Significant differences were found as regards right ventricular diameter (27 +/- 8 vs 22 +/- 5 mm, P < 0.001), left ventricular diameter (41 +/- 9 vs 49 +/- 7 mm, P < 0.001), right over left ventricular diameter ratio (0.67 +/- 0.23 vs 0.43 +/- 0.15, P < 0.0001), tricuspid regurgitant flow peak velocity (2.9 +/- 0.4 vs 2.4 +/- 0.7 m.s-1, P < 0.0001), and abnormal septum motion (12 vs 4, P < 0.01). Multivariate analysis of echocardiographic data included a tricuspid regurgitant flow peak velocity greater than 2.5 m.s-1 and a right over left ventricular diameter ratio greater than 0.5 in a logistic model (sensitivity 93%, specificity 81%). The combination of echocardiographic and non-echocardiographic data included the two previous echocardiographic variables, together with signs of deep vein thrombosis, a deep S wave in lead D1, and a Q wave in lead D3 on the electrocardiogram in a logistic model (sensitivity 96%, specificity 83%). It can be concluded that emergency echocardiography, alone or combined with clinical examination and electrocardiogram, satisfactorily predicts acute pulmonary embolism.

Acute Disease↗
PubMed1996

[Outcome predictive factors at six months for patients over 75 years admitted for emergency care].

A sample of 199 elderly patients (over 75) admitted to emergency care sections of the Marne's (French department) public hospitals were monitored over six months. The purpose of this study was to assess the factors predicting death or institutionization of elderly patients, in order to improve patient care. Surveys were carried out to collect information on health, standards of living, family surrounding and background, social support and level of dependence. After 6 months, 63 (32%) have died and 19 (12.5%) have been directed to institutions. Risk of death factors are primarily connected with the environment. The risk was multiplied by three for patients placed in institutions and absence of children's visit increased the risk by seven. Dependence was also a risk factor. On the other hand, age and clinical diagnosis had little effect. Risk factors for institutionalization were: admission over the week end (OR = 29), non-accompanied (OR = 31), altered mental abilities (OR = 14), absence of children's visit (OR = 22). These predictors will render possible the rapid identification of high risk patients in every day practice. The improvement of gerontological competences in emergency care sections should enable quicker, more inclusive and adapted care. Measures to stimule or substitute for the failing natural relational network of elderly patients are also needed.

Activities of Daily Living↗
PubMed1995

Metabolism and blood-brain clearance of L-3,4-dihydroxy-[3H]phenylalanine ([3H]DOPA) and 6-[18F]fluoro-L-DOPA in the rat.

6-[18F]fluoro-L-DOPA (FDOPA) has been used as a tracer for the cerebral activity of L-3,4-dihydroxyphenylalanine (DOPA)-decarboxylase in studies of positron emission tomography (PET). However, the substitution of fluorine on the aromatic ring may alter the disposition and metabolism of FDOPA from that of endogenous DOPA. In the present study, the kinetics of the peripheral metabolism and the facilitated unidirectional blood-brain clearance of [3H]DOPA and FDOPA were compared in Wistar rats pretreated with carbidopa. In arterial plasma, FDOPA was O-methylated with an apparent rate constant (0.031 min-1) 3-fold that of [3H]DOPA in the same rats. The O-methylated metabolite of FDOPA (OMe-FDOPA) was eliminated from plasma at a rate constant (0.018 min-1) 3-fold that of OMe-[3H]DOPA. The mean unidirectional blood-brain clearance of FDOPA (4.5 mL.hg-1.min-1) in six brain regions was 60% higher than that of [3H]DOPA.

Animals↗
PubMed1995

Health promotion in France. Toward a new way of giving medical care.

Health promotion is not a concept often encountered in France, especially in university teaching hospitals. In fact, the spontaneous orientation of healthcare services tends to emphasize high-technology care, rather than preventive care. This article describes the main characteristics of the French healthcare system, some new elements of its health policy, and a specific experiment of health promotion in a new geriatric hospital.

Aged↗
PubMed1995

Recombinant retroviral vector interferes with the detection of amphotropic replication competent retrovirus in standard culture assays.

Many protocols for gene therapy employ recombinant retroviral vectors, which are replication-defective retroviruses engineered to serve as gene delivery vehicles. The use of retroviral vectors for human gene therapy requires careful screening of vector-producing cell lines and culture supernatants to ensure the absence of replication competent retrovirus (RCR) in clinical products. In this study we have examined several different culture assays routinely used to test for the presence of RCR. Results indicate that cocultivation of a vector-producing cell line with a permissive cell line can reproducibly detect a low level of contaminating RCR. RCR was detected less frequently in direct tests of cell-free culture supernatants from a contaminated vector-producing line. Further studies revealed that recombinant retroviral vector can interfere, to varying degrees, with the detection of low-level RCR in culture supernatants when a marker rescue assay, an extended mink S+L- assay or a PG-4 S+L- assay is used. Interference can be partially overcome by culturing the vector preparation with a permissive cell line for several days before testing on the indicator cell line. The interference phenomenon we have observed may also occur in other culture assays routinely used for the detection of RCR.

Animals↗
PubMed1994

[Cardiac anomalies in disseminated lupus erythematosus diagnosed by Doppler ultrasonography. Prevalence and association with antiphospholipid syndrome].

OBJECTIVES: Antiphospholipid antibodies in patients with systemic lupus erythematosus (SLE) are widely associated with thrombosis, recurrent abortions and a thrombocytopenia. The purpose of this study was first to evaluate the prevalence of cardiac abnormalities in patients with SLE and secondly to establish the relationship between the findings and the presence of an antiphospholipid syndrome. SUBJECTS AND METHODS: First of all, a total of 52 consecutive patients with SLE and 52 healthy sex-and-age-matched control subjects were evaluated in a cross sectional study. All underwent M mode and two dimensional echocardiography, color flow imaging, pulsed and continuous wave Doppler. Secondly, in the SLE group, subjects exposed to antiphospholipid syndrome (n = 20) were compared to the control subjects. RESULTS: Compared with the control group, patients with SLE had significantly more pericardial abnormalities [(p = 0.0006) RR [3.36-infinity], mitral regurgitation [(p = 0.032) RR 2.48 [1.25-5.6]], tricuspid regurgitation [(p = 0.0016) RR 2.41 [1.58-8.85]. There was no significant difference between both groups for the left ventricular mass (p = 0.07), posterior wall (p = 0.25) and interventricular septum dimension (p = 0.16), and mitral valve thickness (p = 0.66). The antiphospholipid syndrome was significantly associated with increased left ventricular mass (p = 0.0054), posterior wall (p = 0.022) and interventricular septum dimension (p = 0.026). The relative risk increased for tricuspid and pulmonary regurgitation in SLE patients who had the antiphospholipid syndrome. CONCLUSION: The prevalence of left ventricular hypertrophy and right heart valvular regurgitation is significantly raised in SLE patients who have the antiphospholipid syndrome. However, antiphospholipid syndrome does not modify the prevalence of pericardial abnormalities which seems to be due to SLE alone.

Adult↗
PubMed1994

Recombinant retroviral vector delivered intramuscularly localizes to the site of injection in mice.

A murine retroviral vector encoding the human immunodeficiency virus type 1 (HIV-1) env and rev genes can be used to induce cytotoxic T lymphocyte responses. Immune responses can be induced by an ex vivo treatment, in which autologous cells are transduced in vitro and re-introduced to the donor, or by direct administration of retroviral vector via intramuscular injection. In this study we have used polymerase chain reaction (PCR) analysis to examine the distribution of recombinant murine retrovirus directly administered to mice. Mice were injected intramuscularly with HIV-IT(V), an amphotropic murine leukemia virus (MLV)-based retroviral vector carrying the HIV-1 env/rev genes and a neomycin resistance marker gene. Detection of the HIV-1 env gene in DNA isolated from injection sites demonstrated in vivo transduction. No evidence of transduction was observed in the testes, spleen, kidney, or thymus. Retroviral DNA was detected in the liver of one animal in the study. These data suggest that retroviral vector administered intramuscularly to mice localizes primarily to the site of injection and that measurable transduction in the testes does not occur.

Animals↗
PubMed1994

Prevalence of valvular involvement in systemic lupus erythematosus and association with antiphospholipid syndrome: a matched echocardiographic study.

Antiphospholipid antibodies in patients with systemic lupus erythematosus (SLE) are often associated with thrombosis, recurrent abortions and thrombocytopenia. The purpose of this study was to evaluate the prevalence of cardiac valvular abnormalities in patients with SLE and to establish the relationship between the echographic findings and the presence of an antiphospholipid syndrome. A total of 52 consecutive patients with SLE and 52 healthy sex- and age-matched controls were therefore evaluated in a cross-sectional study. All underwent M-mode and two-dimensional echocardiography, color-flow imaging, pulsed and continuous-wave Doppler. In the SLE group, subjects exposed to antiphospholipid syndrome (n = 20) were compared to controls. Patients with SLE had significantly more mitral (p = 0.032; RR 2.48; 1.25-5.6) and tricuspid regurgitations (p = 0.0016; RR 2.41; 1.58-8.85). There was no significant difference between either group for mitral valve thickness (p = 0.66). The antiphospholipid syndrome was significantly associated with increased relative risk for tricuspid.

Adolescent↗