Distinct patterns of Th2 cytokine production during immune activation in pediatric liver allograft recipients.
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Biomedical subjects
Publications and source records attributed to T Lang.
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A prospective study was organized in two teaching hospitals in Paris, including 426 elderly patients aged 75 and more, who had been hospitalized through the medical emergency department. The goal of the study was to assess the influence of difficulties of orientation at discharge on the length of stay, independently of other risk factors. The mean length of stay was 18.3 +/- 15.4 days. Orientation at discharge toward a social or a nursing care institution was associated with a 12 days longer mean length of stay than a home discharge. A longer length of stay was also associated with: a strictly social problem at admission, the diagnoses of dementia, confusion, social problem, fall or general health impairment, a short or long-term fatal prognosis, a poor mental status, refusal of home discharge as expressed by the referent person. Multivariate analysis showed that discharge toward a social or a nursing care institution was the first explanatory factor, explaining 12% of variance. These results suggest that the hospital discharge management has a major influence on the elderly length of hospital stay. Therefore, an interdisciplinary care management, including social and geriatric evaluation as soon as the patient is admitted at the emergency department, should be evaluated, in order to avoid problems of orientation that may occur at discharge.
The intraphagosomal survival strategy of pathogenic mycobacteria was studied in bone marrow-derived mouse macrophages. These bacteria survive inside phagosomes by interfering in an unknown manner with phagosome processing which normally would lead to digestion of the phagocytic particle in phagolysosomes. Here, phagosome processing was compared for different phagocytic particles: live Mycobacterium avium, degradable Bacillus subtilis, or indigestible latex beads. We show detailed electron microscopic morphological observations which characterize various phases of interaction between endocytic organelles and phagosomes. We measured fusion of phagosomes with early endosomes or with lysosomes by using newly internalized endocytic contents (horseradish peroxidase, HRP) and membrane marker (plasma membrane glycoconjugates labeled with [3H]galactose via exoglycosylation). Morphometric analysis of these observations showed that the nature of the phagocytic particle affects phagosome processing: As long as particles remain undigested, maturation of phagosomes is prevented and they remain fusogenic towards early endosomes; concurrent to particle digestion, phagosome processing proceeds towards transfer of phagocytic contents to phagolysosomes which display kinetic and compositional characteristics of lysosomes. As an intact phagocytic particle, M. avium remains in non-matured phagosomes which fuse with early endosomes, but not with lysosomes. Fusion with early endosomes is reduced, thereby indicating the stage where this endoparasite exerts its effect.
Antigen 90K is produced by several tumor-cell lines and by patients with cancer. Its function has not yet been clarified, although recent reports suggest that it plays a role in the tumor-host relationship--for example by stimulation of natural killer and lymphokine-activated killer-cell activity. Previous studies have indicated that 90K expression may be under the influence of interferon-alpha. Here, we provide evidence that both interferon-alpha and -gamma can enhance the secretion of 90K and augment the level of specific mRNA expression in 3 ovarian carcinoma cell lines (OVCAR-3, HTB-77 and SKOV-6). However, interferon-gamma leads to depletion of cellular 90K whereas interferon-alpha increases both secreted and cellular 90K levels. In equimolar concentrations, Interferon-alpha was always superior to interferon-gamma in augmenting 90K protein or mRNA levels. Combinations of TNF with interferon-gamma were highly synergistic both in reducing cell proliferation and in increasing 90K secretion and mRNA expression. This synergism was seen to a lesser extent with interferon-alpha.
High blood pressure in black subjects has been recognized as a clinical entity because of high prevalence, frequent severe complications and pathophysiological and therapeutic specificities. Results from 52 centers in 32 countries show wide variability. In the black population in United States, mean systolic and diastolic blood pressure levels are high, 128/81 mmHg, with a prevalence of hypertension reaching 33.5%, while an ethnic population in Kenya has low mean levels, 110/68 mmHg, with a hypertension prevalence of only 5%. Complications have been reported to be more frequent in black populations. In the United States, in comparison with the white population morbidity due to left ventricular hypertrophy is increased by 2, end-stage renal failure by 4.2 and mortality due to cerebral vascular diseases by 1.5. However, risk factors including over-weight, alcohol consumption, sodium intake and the socioeconomic environment have been shown to explain most of the differences between the white and the black populations. Differences in diagnosis and management may also play a role. Indeed, while genetic selection may have had an effect, there is no current scientific data which would justify using the colour of the skin as a genetic marker for high blood pressure.
Psychogenic loss of consciousness often leads to clinical situations where making decisions is difficult and psychiatric consultation becomes necessary. The function of the consultation/liaison-psychiatrist consists in rendering information from the psychosocial context comprehensible after establishing a first contact with the patient and his family and after the first psychiatric assessment. In a second step, the CL-psychiatrist then may make further recommendations how to deal with the patient, possibly not only in a patient-centered, but also team-centered manner. This article demonstrates a possible approach and differential diagnosis in the light of two clinical case reports. The theoretical part defines and classifies psychogenic loss of consciousness. It then deals with disorders of consciousness in epilepsy and the psychodynamics of psychogenic seizures as a subconscious expression of unbearable or unsolvable conflicts.
In a retrospective study involving 59 patients, a regression equation between nail length and body weight has been computed as follows: nail length = -5.05729 + 0.222 x body height (probability value for intercept P = 0.24327 and slope P = 0.0000). Graphic analysis of the residuals gave a randomly scattered blob of data points. Validation of the equation in 12 patients showed an average difference between actual and derived nail length of -0.09 (SD 0.93, minimum -1.57, maximum 1.42). It can be stated that in most cases of intramedullary tibial nailing, the length of nail required can be predicted by the regression equation using the available manufactured nail of the size nearest in length to the derived length or the next size up or down.
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Macrophages, being apparently the only cells that in vivo allow the growth of the intracellular pathogen Leishmania, are likely candidates to present antigens to Leishmania-specific CD4+ and CD8+ T lymphocytes, known to be involved in the resolution or in the development of lesions induced by these parasites, and recognizing processed antigens bound to MHC class I and MHC class II molecules, respectively. In the present study, we analysed by confocal microscopy and by immunoelectron microscopy the subcellular distribution of both MHC class I and class II molecules in mouse (Balb/c and C57BL/6 strains) bone marrow-derived macrophages infected for 12 to 48 hours with Leishmania amazonensis amastigotes and activated with gamma interferon to determine the intracellular sites where Leishmania antigens and MHC molecules meet and can possibly interact. Double labelings with anti-MHC molecule antibodies and with either propidium iodide or an anti-amastigote antibody allowed localization of MHC molecules with regard to the endocytic compartments housing Leishmania amastigotes, organelles known as the parasitophorous vacuoles (PV) and which most likely contain the highest concentration of parasite antigens in the host cell. Both uninfected and infected macrophages from Balb/c mice expressed the MHC class I molecules H-2Kd and H-2Dd on their cell surface but no significant amount of these molecules could be detected in the PV, which indicates that, if infected macrophages play a role in the induction of Leishmania-specific CD8+ T lymphocytes, PV are probably not loading compartments for MHC class I molecules. In contrast, MHC class II molecules were found to be associated with the PV membranes as shown previously with microscopic techniques at lower resolution (Antoine et al. Infect. Immun. 59, 764-775, 1991). In addition, we show here that, 48 hours after infection of Balb/c macrophages, in about 90% of PV containing MHC class II molecules, the latter were mainly or solely localized at the attachment zone of amastigotes to PV membranes. This peculiar distribution, especially well demonstrated using confocal microscopy, was confirmed by subcellular fluorescence cytometry of infected macrophages stained for the MHC class II molecules. The following data agree with the idea that PV-associated MHC class II molecules establish specific interactions with plasma membrane components of amastigotes. First, the polarized localization of class II appeared specific to these molecules, since the distribution of the lysosomal glycoproteins Igp110 and Igp120, of the macrosialin (a macrophage-specific marker of endocytic compartments) and of the GTP-binding protein rab7p, shown here as being PV membrane components, was homogeneous.(ABSTRACT TRUNCATED AT 400 WORDS)
Leishmania donovani amastigotes, the etiological agents of visceral leishmaniasis, are obligate intracellular parasites residing in membrane-bound compartments of macrophages called parasitophorous vacuoles (PV). The study of these organelles is of paramount importance to understanding how these parasites resist the microbicidal mechanisms of macrophages and how they escape the immune response of their hosts. Confocal microscopy of mouse bone marrow-derived macrophages infected with L. donovani amastigotes and stained for various prelysosomal/lysosomal markers and for major histocompatibility complex (MHC) molecules was used to define PV with respect to the endocytic compartments of the host cells and to address the issue of their potential role in antigen processing and presentation. Forty-eight hours after infection, many PV contained cathepsins B, D, H and L and they were all surrounded by a membrane enriched for the lysosomal glycoprotein lgp120/lamp 1 but apparently devoid of the cation-independent mannose 6-phosphate receptor, a membrane protein generally absent from the lysosomes. These data suggested that PV acquire within 48 hours the characteristics of a lysosomal compartment. However, both macrosialin and the GTP-binding protein rab7p (specific markers of the prelysosomal compartment) were found to be highly expressed in/on PV membrane. Thus, at this stage, PV appear to exhibit both lysosomal and prelysosomal features. Infected macrophages activated with IFN-gamma before or after infection showed PV strongly stained for MHC class II molecules but not for MHC class I molecules. This suggests that, if infected macrophages can act as antigen-presenting cells for class I-restricted CD8+ T lymphocytes, Leishmania antigens must exit the PV. MHC class II molecules reached the PV progressively, indicating that they were not plasma membrane-bound molecules trapped during internalization of the parasites. The redistribution of class II observed in infected cells did not alter their quantitative expression on the plasma membrane at least during the first 48 hours following the phagocytosis of the parasites. The invariant chains, which are transiently associated with class II molecules during their intracellular transport and which mask their peptide-binding sites, did not reach PV or were rapidly degraded in these sites, suggesting that PV-associated class II are able to bind peptides. This last assumption is strengthened by the fact that class II located in PV could bind conformational antibodies that preferentially recognize class II with tightly associated peptides.(ABSTRACT TRUNCATED AT 400 WORDS)
Parallel with a marked escalation in the number of injuries of the skull, shoulder girdle and upper extremities in recent years, the incidence of spinal injuries has also intensified. This is due to an increase in speed and deceleration traumas, such as are particular to collision accidents. Of all patients with winter sports injuries at the Department of Traumatology at Innsbruck University Hospital, 4.9% have a spinal trauma. A retrospective ten-year study was undertaken to analyze the surgically treated spinal injuries out of overall winter sports injuries. Between 1982 and 1992 862 spinal injuries were surgically treated, 10.9% (94) of which were suffered in winter sports accidents. Of these winter sports injuries, 81.7% (76) were due to skiing accidents. The age group 15 to 25 years made up the largest contingent at 39.8% (37). Most spinal traumas (47.3%), whether suffered in winter sports or not, were located in the thoracolumbar region or the lumbar part of the spine, followed by 38.7% at the cervical vertebrae. Serious snowboard accidents are especially predestined for injuries of the cervical vertebrae. The age group 51 to 60 years also shows a trend to injure the cervical vertebrae; degenerative changes present in this age span cause a high percentage of accompanying neurological injuries. More than half (52.7%) of all surgically treated spinal injuries showed some loss or impairment of neurological function at the time of admission; 17.2% of these cases showed symptoms of a complete transverse lesion of the cord. 36% of all serious spinal injuries are accompanied by secondary injuries (such as craniocerebral trauma, thoracic trauma and other fractures).(ABSTRACT TRUNCATED AT 250 WORDS)
Formation of sublytic terminal complement complexes (TCC) on nucleated cells produces transient increase in [Ca2+]i and activates protein kinase C. The present study is to evaluate whether TCC can generate endogenous signal messengers other than Ca2+ that regulate cell activities by measuring mass-levels of sn-1,2-diacylglycerol (DAG) and ceramide. As targets, lymphoblastoid human B cell lines JY25 and its mutant JY5 were used. JY5, cells deficient in glycosylphosphatidylinositol-anchored proteins with higher lytic susceptibility to human complement, are four times more efficient in forming C5b-9. When cells sensitized with limited anti-class II IgG were exposed to human serum to generate sublytic TCC, a sustained increase in DAG and ceramide was observed with a maximum 3.6-fold DAG increase over basal level in JY25 and 2.8-fold in JY5, and 6.3-fold ceramide increase in JY25 and 2.8-fold in JY5. The effect of TCC was evaluated with C7-deficient human serum (C7D) +/- C7 and also with C5b6, C7, C8, and C9 proteins. The DAG and ceramide increase by C7D + C7 over C7D control were 1.6- and 1.8-fold, respectively, in JY25, and 2.3-, and two-fold in JY5. TCC activation also induced an increased hydrolysis of sphyingomyelin and phosphatidylcholine. In addition, DAG increase by TCC was primarily achieved by C5b-7 and preincubation of cells with pertussis toxininhibited DAG increase, suggesting an involvement of a pertussis toxin-sensitive GTP-binding protein. As important signal transduction molecules, DAG and ceramide generated in response to TCC assembly, could participate in cell activation during inflammation and repair.
The objectives of this prospective study were to investigate the value of the immediate closed reduction following fractures of the thoracolumbar and lumbar region. To reach that goal we performed a two stage CAT scan procedure before and after the reduction maneuver in a distinct patient population. The aim was not only to investigate the biomechanical process but also to evaluate and describe certain fracture types which have a good prognosis due to closed reduction according to posttraumatic spinal stenosis because of protruding posterior wall fragments and those who fail, respectively.
STUDY OBJECTIVE: The aim was to assess the frequency of sleep disorders in relation to working conditions. DESIGN: This was a cross sectional study. Data were collected prospectively, on a standardised form, by 13 occupational physicians. The quality of sleep was assessed by self perceived sleep disturbances and consumption of sleeping tablets. Working conditions were described by the worksite physician as well as by the participants. SETTING: 2769 small or medium sized firms in the Paris area. PARTICIPANTS: A random sample of 7629 wage earners was studied. Among the participants, 61% were men and 39% women; 44% were blue collar workers. MAIN RESULTS: The prevalence of sleeping tablet consumption was 6.1% and 11.3% respectively for men and women. Sixteen percent of men and 26% of women stated that they had sleep disturbances (p < 0.001). In both sexes, drug consumption and sleep disturbances increased with age and were highest among individuals aged 55 years and more. No association between working conditions (exposure to noise, assembly line working, or physical workload) and sleep disturbances or drug consumption was found. Sleeping tablet consumption was higher among subjects reporting a bad atmosphere at work; the same was true for men with little interest in their job and for women working under time pressure. For both sexes, subjects reporting any of these conditions were more likely to report sleep disturbances. CONCLUSIONS: A high prevalence of self reported sleep problems and related drug consumption was observed. Physical working conditions were not related to the quality of sleep in contrast to perceived job conditions. The results suggest that sleep quality might be a useful health indicator for the occupational physician.
The objective of the study was to assess the prevalence of unclassified hypertension during pregnancy and its consequences on infant's health in an African urban setting: Pikine, a suburb of Dakar, Senegal. A cross-sectional study of a random sample of pregnant women and a prospective study, from the inclusion to seven days after delivery, were performed. 886 women attending the prenatal centers were included in the cross-sectional study. 471 pregnant women were included in the follow-up study. The prevalence of DBP > or = 120 mmHg was 0.7%; 5.7% of the women had DBP > or = 95 mmHg. Longitudinal data were available for 425 deliveries. Two spontaneous abortions, 25 stillbirths, and 12 deaths during the early neonatal period were recorded. Among babies living at birth, the percentage of LBW (> or = 2500 g) was 8.5%. The percentages of adverse outcome of pregnancy (death and/or low birth weight) was associated with mothers' diastolic BP: < 85 mmHg: 13%; 85 to 89: 16%; 90 to 94: 9%; DBP > or = 95: 32%, (p < 0.01). Using 95 mmHg as a cutpoint, the relative risk of adverse outcome associated with a DBP > or = 95 mmHg was 2.5 (CI 95%: 1.4-4.3). This risk was significantly increased among women who reported difficult living conditions. Eight percent of the adverse outcomes of pregnancy, 10% of the low birth weights and 8% of the perinatal mortality were found to be associated with DBP > or 95 mmHg.
Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. We, therefore, investigated whether increases of bile acid or phospholipid concentrations in bile by in vitro supplementation affect the cholesterol nucleation time. Bile samples were obtained at surgery from patients with cholesterol gallstones. Prior to the nucleation assay the bile samples were divided into 0.5-ml aliquots and supplemented with 1.25, 2.5, 5.0, and 10.0 mumol/ml of different phosphatidylcholines (PC-dimyristoyl, PC-dipalmitoyl, PC-distearoyl, and extracted biliary PCs) or with 5.0, 10.0, and 20.0 mumol/ml of bile acids (glycine or taurine conjugates of cholic acid, deoxycholic acid, or chenodeoxycholic acid). The increase of phosphatidylcholine or bile acid concentration decreased the mean cholesterol saturation index to a similar extent (PC: 0.1-0.3; BA: 0.1-0.2). Supplementations of bile with increasing amounts of synthetic or biliary PCs caused a marked prolongation of the nucleation time in bile from 1.5 +/- 0.2 up to > or = 21 days or 2.5 +/- 0.7 up to > or = 21 days. Concurrently, biliary cholesterol was shifted from vesicles to mixed micelles and the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. In contrast, the addition of bile acids to gallbladder bile did not affect the cholesterol nucleation time (2.2 +/- 0.3 days), the percentage of vesicular cholesterol, or the cholesterol/phospholipid ratio of vesicles and micelles.(ABSTRACT TRUNCATED AT 250 WORDS)
Rheumatological complications are sometimes disabling in heart transplant recipients and may negate the good results obtained with transplantation. The objective of this study was to evaluate the incidence of these complications. 365 consecutive heart transplant recipients (292 males and 73 females) were systematically interviewed and examined according to a standardized protocol. The mean age of the patients was 45.9 +/- 12.0 years (range: 11-68). The mean duration from transplantation to time of the study was 35.8 +/- 25.6 months (range: 1-115). The rheumatological disorders most frequently encountered were: gout, osteoporosis, osteonecrosis and myalgias. Early-onset polyarticular gout was diagnosed in 63/365 patients (17.3%). This diagnosis was significantly associated with patient's age, time since transplant, male sex, serum uric acid, serum creatinine, diuretics intake and inversely associated with the serum cyclosporin levels. Hyperuricemia was observed in 75.9% of transplant recipients with a mean of 507.5 +/- 132.5 mumol/l (range: 97-965). An osteoporotic fracture was present in 18/365 patients (4.9%) and was significantly associated with the patient's age, but not with the dose of corticosteroids. Osteonecrosis was detected in 10/365 patients (2.7%), always affected the hip, and was significantly associated with the patient's age, but not with the high doses of steroids. Myalgias were reported by 14/365 patients (3.8%). Laboratory, electromyographic and histological analysis were negative. Rheumatological complications are frequent in heart transplant recipients and justify preventive and therapeutic management.