Nonunion of tibial stress fractures in patients with deformed arthritic knees.
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Biomechanical Phenomena↗
Biomedical subjects
J Bernard
Publications and source records attributed to J Bernard.
[Pulmonary sarcoidosis diagnosed in 2 cases suspected to be neoplasms].
Two young patients suspected of neoplasms were admitted to Thoracic Surgery Department of Institute of Tuberculosis in first case (35-years old woman) chest x-ray showed atelectasis of upper right lobe, enlarged lymph nodes of mediastinum and right hillium-lymphoproliferative process was suspected. Repeated bronchoscopies revealed narrowing of upper right bronchus and in biopsy--granulomas with small focus of necrosis were found. Tuberculosis was not excluded. During short antituberculous treatment progression of lung lesions and enlarged supraclavicular lymph node were observed. Following biopsy confirmed sarcoidosis. Treatment with prednisone was successful. In second case the chest x-ray showed large masses in both lungs suspected of seminoma metastases. Lung biopsy made during thoracotomy revealed sarcoidosis.
Adult↗
[Apropos of Plasmodium falciparum malaria].
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Antimalarials↗
Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression.
We report the existence of eight different interleukin-15 receptor alpha-chain (IL-15Ralpha) transcripts resulting from exon-splicing mechanisms within the IL-15Ralpha gene. Two main classes of transcripts can be distinguished that do or do not (Delta2 isoforms) contain the exon 2-coding sequence. Both classes were expressed in numerous cell lines and tissues (including peripheral blood lymphocytes) at comparable levels and could be transcribed in COS-7 cells, and the proteins were expressed at the cell surface. Both receptor forms displayed numerous glycosylation states, reflecting differential usage of a single N-glycosylation site as well as extensive O-glycosylations. Whereas IL-15Ralpha bound IL-15 with high affinity, Delta2IL-15Ralpha was unable to bind IL-15, thus revealing the indispensable role of the exon 2-encoded domain in cytokine binding. A large proportion of IL-15Ralpha was expressed at the nuclear membrane with some intranuclear localization, supporting a potential direct action of the IL-15.IL-15Ralpha complex at the nuclear level. In sharp contrast, Delta2IL-15Ralpha was found only in the non-nuclear membrane compartments, indicating that the exon 2-encoded domain (which is shown to contain a potential nuclear localization signal) plays an important role in receptor post-translational routing. Together, our data indicate that exon 2 splicing of human IL-15Ralpha is a natural process that might play regulatory roles at different levels.
Animals↗
Antigen receptor engagement selectively induces macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta chemokine production in human B cells.
We show herein that B cell Ag receptor (BCR) triggering, but not stimulation by CD40 mAb and/or IL-4, rapidly induced the coordinated expression of two closely related T cell chemoattractants, macrophage inflammatory protein-1 beta (MIP-1 beta) and MIP-1 alpha, by human B cells. Naive, memory, and germinal center B cells all produced MIP-1 alpha/beta in response to BCR triggering. In contrast to MIP-1 alpha/beta, IL-8, which is spontaneously produced by germinal center B cells but not by naive and memory B cells, was not regulated by BCR triggering. Culturing follicular dendritic cell-like HK cells with activated B cells did not regulate MIP-1 alpha/beta production, but it did induce production of IL-8 by HK cells. Microchemotaxis assays showed that CD4+CD45RO+ T cells of the effector/helper phenotype actively migrated along a chemotactic gradient formed by BCR-stimulated B cells. This effect was partially blocked by anti-MIP-1 beta and anti-CC chemokine receptor 5 Ab, but not by anti-MIP-1 alpha Ab suggesting that MIP-1 beta plays a major role in this chemoattraction. Since maturation of the B cell response to a peptide Ag is mostly dependent on the availability of T cell help, the ability of Ag-stimulated B cells to recruit T cells via MIP-1 alpha/beta, may represent one possible mechanism enabling cognate interactions between rare in vivo Ag-specific T and B cells.
Antibodies, Anti-Idiotypic↗
The green fluorescent protein targets secretory proteins to the yeast vacuole
The green fluorescent protein (GFP) was used as a marker to study the intracellular transport of vacuolar and secretory proteins in yeast. Therefore, the following gene constructs were expressed in Saccharomyces cerevisiae under control of the GAL1 promoter: GFP N-terminally fused to the yeast secretory invertase (INV-GFP), the plant vacuolar chitinase (CHN-GFP) and its secretory derivative (CHNDeltaVTP-GFP), which did not contain the vacuolar targeting peptide (VTP), both chitinase forms (CHN and CHNDeltaVTP), GFP without any targeting information and two secretory GFP variants with and without the VTP of chitinase (N-GFP-V and N-GFP). Whereas chitinase without VTP is accumulated in the culture medium the other gene products are retained inside the cell up to 48 h of induction. Independently of a known VTP they are transported to the vacuole, so far as they contain a signal peptide for entering the endoplasmic reticulum. This was demonstrated by confocal laser scanning microscopy, immunocytochemical analysis and subcellular fractionation experiments as well. The transport of the GFP fusion proteins is temporary delayed by a transient accumulation in electron-dense structures very likely derived from the ER, because they also contain the ER chaperone Kar2p/Bip. Our results demonstrate that GFP directs secretory proteins without VTP to the yeast vacuole, possibly by the recognition of an unknown vacuolar signal and demonstrates, therefore, a first limitation for the application of GFP as a marker for the secretory pathway in yeast.
Journal Article↗
Measurement of bone mineral density by dual X-ray absorptiometry in Paget's disease before and after pamidronate treatment.
Third-generation bisphosphonates are now currently used in the treatment of Paget's disease of bone. Dual X-ray absorptiometry may make it possible to quantify the action of these bisphosphonates on bone mineral density (BMD) in pagetic and nonpagetic bone. We used Lunar DPX, a total-body software program (automatic analysis and/or manual windows according to the site and bilateral or unilateral pagetic involvement) to study BMD in 28 patients (18 men, 10 women, mean age 69.8 years) with Paget's disease before and 6 months after infusions of 60 mg (alkaline phosphatase <350 IU) or 120 mg (ALP >350 IU) of pamidronate. Before treatment, in the 28 patients, the BMD of trabecular pagetic bone was 25% higher than that of nonpagetic bone; in cortical pagetic bone the BMD was 35% higher. After treatment, the BMD of trabecular pagetic bone increased by only 1.17%. the BMD of cortical pagetic bone increased by 1.37% whereas nonpagetic cortical bone lost 0.84%, independently of the levels of parathyroid hormone or the administration of calcium and vitamin D.
Absorptiometry, Photon↗
Induction of cellular immunosuppression by the human papillomavirus type 16 E7 oncogenic protein.
The human papillomavirus type 16 (HPV-16) E7 oncogenic protein is found in the culture supernatant of SiHa cells, a cervical carcinoma cell line. Extracellular E7 protein, acting as a viral toxin in human immune cells, induces the overproduction of the immune suppressive IFN alpha cytokine by APCs, and inhibits the T-cell response to recall and allogenic antigens. These effects should be taken into account for the design of anti-human cervical carcinoma vaccines.
Animals↗
HPV-16 E7 but not E6 oncogenic protein triggers both cellular immunosuppression and angiogenic processes.
HPV-16 E6 and E7 oncoproteins impair the cell cycle in human uterine cervix carcinoma cells (HUCC) by acting on p53 and retinoblastoma proteins, respectively. We recently reported that E7 related into the extracellular compartment by HUCC SiHa cells could inhibit immune T-cell response to recall and alloantigens by a mechanism involving an overproduction of the immunosuppressive IFN alpha by antigen presenting cells (APCs). In this study, we found that besides E7, E6 protein and the vascular endothelium growth factor (VEGF) were released into the SiHa cell supernatants, and we further showed that extracellular E7 but not E6 oncoprotein 1) inhibits the immune cell response to recall and alloantigens, and 2) enhances the release of angiogenic cytokines, including TNF alpha, IL-1 beta and IL-6 by macrophages and/or dendritic cells. VEGF unexpectedly released by cancer cells could also contribute to angiogenesis. Thus in HUCC the same E7 oncoprotein which contributes to controlling the cancer cell cycle has the means in its extracellular configuration to contribute to microenvironmental immunosuppressive and angiogenic processes. Neutralizing anti-E7 antibodies either passively administered or induced by active immunization could represent a new immunotherapeutic endeavour to combat the immunosuppression and/or neoangiogenesis effects of extracellular E7 protein.
Cytokines↗
The comparative efficacy and tolerability of CGP 56697 (artemether + lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the Tropics to The Netherlands and France.
CGP 56697 (Riamet) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4 x 4 tablets over 48 h, was compared to halofantrine, given as 3 x 2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n = 51) or halofantrine (n = 52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P < 0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P < 0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P = 0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (> 30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptablyhigh (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days.
Adolescent↗
Antitumour immune response and cancer vaccination: the critical role of dendritic cells.
Increasing the capacity of the immune system to mediate tumour regression has been a major goal in tumour immunology. Progress towards this goal has been recently aided by the identification of immunogenic cancer antigens and by a better understanding of the mechanisms of T-cell immune response and tumour escape. A rare antigen-presenting cell--the dendritic cell (DC)--appears to be the key to these mechanisms. The possibility of generating these cells in vitro from blood precursors has initiated a new era in cancer immunotherapy. Using DC as a cancer vaccine adjuvant has led to reports of measurable immune responses, and, in a few cases, to complete disease responses in patients with B-cell lymphoma and melanoma.
Antigens, Neoplasm↗
Prevalence of respiratory symptoms and increased specific IgE levels in West-African workers exposed to isocyanates.
Respiratory symptoms and immunological effects from chronic exposure to isocyanates (toluene diisocyanate) were studied in a cross survey of workers from West African factories producing paints and polyurethane foam. A questionnaire, a pulmonary function test, immunoglobulin E (IgE) levels, radioallergosorbent test (RAST) and an atmospheric sample to quantify isocyanate exposures were carried out in the workplace for each worker. Ninety-six workers, of whom 44 had occupational isocyanate-induced asthma, were included in the study. Twenty-four viral-infected subjects were excluded from the immunological study. Specific antibodies to isocyanates were detected in two of the symptomatic individuals. This low proportion appeared to be a common feature of this disease. The prevalence of isocyanate-induced asthma in a West African working population appears to be significant in the context of chronic human exposure, as current data are based on excessive acute exposure due to an accident as seen in India.
Adult↗
Interferon alpha and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS.
HIV type 1 (HIV-1) not only directly kills infected CD4(+) T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon alpha (IFNalpha) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNalpha and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNalpha and extracellular Tat. We, therefore, suggest that IFNalpha and Tat may be critical targets for anti-AIDS strategies.
Acquired Immunodeficiency Syndrome↗
C-C chemokines, pivotal in protection against HIV type 1 infection.
Exposure to HIV type 1 (HIV-1) does not usually lead to infection. Although this could be because of insufficient virus titer, there is now abundant evidence that some individuals resist infection even when directly exposed to a high titer of HIV. This protection recently has been correlated with homozygous mutations of an HIV-1 coreceptor, namely CCR5, the receptor for the beta-chemokines. Moreover, earlier results already had shown that the same chemokines markedly suppress the nonsyncitial inducing variants of HIV-1, the chief virus type transmitted from person to person. CCR5 mutation, as a unique mechanism of protection, is, however, suspect because HIV-1 variants can use other chemokine receptors as their coreceptor. Moreover, recent results have established that infection can indeed sometimes occur with such mutations. Here, we report on transient natural resistance over time of most of 128 hemophiliacs who were inoculated repeatedly with HIV-1-contaminated Factor VIII concentrate from plasma during 1980-1985 before the development of the HIV blood test. Furthermore, and remarkably, 14 subjects remain uninfected to this date, and in these subjects we found homozygous CCR5 mutations in none but in most of them overproduction of beta chemokines. In vitro experiments confirmed the potent anti-HIV suppressive effect of these chemokines.
Cells, Cultured↗
Bidirectional modulation of AMPA receptor properties by exogenous phospholipase A2 in the hippocampus.
The synaptic modifications underlying long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission in various brain structures may result from changes in the properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. In the present study, we report that treatment of rat synaptoneurosomes with increasing concentrations of phospholipase A2 (PLA2) produces a biphasic effect on AMPA receptor binding, with low concentrations causing a decrease and high concentrations an increase in agonist binding. Analysis of the saturation kinetics of 3H-AMPA binding revealed that the biphasic effect of PLA2 was due to modifications in receptor affinity and not to changes in the maximum number of binding sites for AMPA receptors. The 12-lipoxygenase inhibitors preferentially reduced PLA2-induced decrease in AMPA binding and treatment of hippocampal synaptoneurosomes with arachidonic acid (AA) or 12-HPETE, the first metabolite generated from the hydrolysis of AA by 12-lipoxygenases, decreased 3H-AMPA binding. Moreover, electrophysiological experiments indicated that the 12-lipoxygenase inhibitor baicalein totally blocked LTD formation in area CA1 of hippocampal slices. The decrease in 3H-AMPA binding elicited by low concentrations of PLA2, as well as the level of LTD, were partially reduced by AA-861, a 5-lipoxygenase inhibitor, while the cyclooxygenase inhibitor indomethacin did not prevent LTD formation or the effects of PLA2 on 3H-AMPA binding. Our results provide evidence for a possible involvement of lipoxygenase metabolites in the regulation of AMPA receptor during synaptic depression. In addition, they strongly support the idea that the same biochemical pathway, i.e., NMDA receptor activation and endogenous PLA2 stimulation, may represent a common mechanism resulting in AMPA receptor alterations for both LTP and LTD formation.
Animals↗
The construction and utility of an amniocentesis trainer.
OBJECTIVE: Our goal was to design an inexpensive amniocentesis trainer for instruction and practice with ultrasonography-assisted needle guidance and the freehand technique. STUDY DESIGN: The amniocentesis trainer was constructed from a commercially available 5.3-L storage box (No. 5805; Rubbermaid Incorporated, Wooster, Ohio). Sonodense sperical targets 2.3 cm in diameter were taped to the bottom, and the box was filled with a gelatin mixture. The box was covered with a rubber membrane from a pelviscopy trainer (United States Surgical Corp, Norwalk, Conn). After the gelatin mixture set overnight at 40 degreesF, the amniocentesis trainer was ready for use. RESULTS: When a needle is introduced through the membrane into the gelatin, the ultrasonographic image is a reasonable simulation of an amniocentesis. The trainer improved the ability of an operator to perform a freehand amniocentesis, orient the ultrasound transducer, follow a needle with continuous ultrasonographic guidance, and hit a 2-cm target. The gelatin also allows for evaluation of improvement between amniocentesis attempts because a faint image of the needle track from prior attempts remains visible. Once basic amniocentesis skills are mastered, the trainer is easily modifiable so that obstacles can be added that could simulate umbilical cord and fetal extremities. CONCLUSIONS: We were able to construct an inexpensive amniocentesis trainer that facilitates instruction in the freehand amniocentesis technique. This trainer enables an operator to master the skills necessary to perform the technique of freehand ultrasonography-guided amniocentesis under direct ultrasonographic visualization without putting a patient through the discomfort of participating in the learning curve.
Amniocentesis↗
Is there a relationship between physical activity and dietary calcium intake? A survey in 10,373 young French subjects.
PURPOSE: The purpose of this study was to discuss, in the light of the results of a survey, the calcium ration of a sample of French youth and to determine whether various sports activities can be related to dietary calcium intake. METHODS: Physical activity was evaluated using Baecke's questionnaire. Calcium intake was evaluated using a food frequency oriented questionnaire. The survey was performed on a population of 10,373 subjects (6,966 males and 3,407 females) including three different groups of subjects: school children and college students, military personnel, and athletes registered in sports federations. The mean age of this population was 19 +/- 9 yr, ages ranging between 7 and 50 yr. RESULTS: The mean amount of declared calcium intake (DCI) for the total population was 1242 +/- 843 mg per 24 hr (mg x d(-1)). Fifty percent of this population consumed less than 1000 mg x d(-1) and 13% less than 500 mg x d(-1). There was no significant relationship between the index of activity and declared calcium intake. Calcium intake decreased with age and was lower in females compared to males. CONCLUSIONS: The subjects trained in individual endurance sports such as triathlon, biking, and road running have a lower DCI than subjects trained in team sports such as volley ball, handball, or basketball. This survey, performed on a large population, does indicate that for half of them daily calcium intake is below the threshold of 1,000 mg x d(-1) considered the daily requirement covering the needs of a population without age or gender distinction and that calcium intake is not related to the level of physical activity.
Adolescent↗
Adherent-free generation of functional dendritic cells from purified blood monocytes in view of potential clinical use.
There is increasing interest in dendritic cells (DC) that are capable of initiating antitumor immune responses. An in vitro cell differentiation method has recently been developed that uses GM-CSF and IL-4 to generate human DC from adherent blood mononuclear cells cultured on tissue culture plastic. These cells are competent for antigen uptake but express relatively low levels of co-stimulatory molecules and thus correspond to immature resident tissue DC. We have adapted this method to consider some variables that are pertinent to clinical use, including a large scale differentiation of functional DC in a culture system suitable for clinical use. We report here that sizable numbers of monocytes purified by elutriation from blood leukocytes and cultured in Teflon bags develop with high efficiency into typical DC, as defined by morphology and membrane phenotype. When compared with usual adherent DC, cells generated under our adherent-free conditions exhibited lower CD1a expression and antigen capture capacity, but maintained the ability to present soluble antigens to T cells. They neoexpressed a high level of the co-stimulator molecule B7-2 (CD86) and was potent accessory cells for T cell proliferation, but they lacked the CD83 marker of DC full maturation. This study may constitute a prerequisite step for clinical investigations in tumor immunotherapy.
Antigens, CD↗