Multidisciplinary treatment of an adult patient with a labiopalatal cleft.
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Adolescent↗
Biomedical subjects
M David
Publications and source records attributed to M David.
Binding of IL-4 to the IL-13Ralpha(1)/IL-4Ralpha receptor complex leads to STAT3 phosphorylation but not to its nuclear translocation.
Interleukin-4 (IL-4) is a pleiotropic cytokine, which acts on both hematopoietic and non-hematopoietic cells, through different types of receptor complexes. In this study, we report that in human B cells, IL-4 caused rapid phosphorylation of Janus kinase (JAK) 1 and JAK3 tyrosine kinases. In keratinocytes, the hematopoietic-specific receptor common gamma(c) chain is not expressed and the IL-13 receptor alpha(1) (IL-13Ralpha(1)) participates in IL-4 signal transduction. In keratinocytes, IL-4 induced JAK1 and JAK2 phosphorylation but, unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling. In both cell types, IL-4 induced phosphorylation and DNA binding activation of the signal transducer and activator of transcription (STAT) 6 protein. Furthermore, IL-4 stimulation of keratinocytes also induced tyrosine phosphorylation of STAT3 which was found to bind to the phosphorylated IL-13Ralpha(1). STAT3 however did not significantly translocate to the nucleus, nor did it bind with high affinity to target DNA sequences.
Cell Line↗
p38-dependent activation of interferon regulatory factor 3 by lipopolysaccharide.
Interferon regulatory factor 3 (IRF3) is known to participate in the transcriptional induction of interferon (IFN) alpha and IFNbeta genes, as well as of a number of interferon-stimulated genes (ISGs), as a result of viral infection. In the present study we demonstrate the activation of IRF3 followed by ISG induction after exposure of cells to the bacterial cell wall component lipopolysaccharide. Engagement of Toll-like receptors by lipopolysaccharide triggered the nuclear translocation of IRF3, followed by its DNA binding and the subsequent induction of several interferon-regulated genes. Transcriptional activation of ISGs occurred in a protein synthesis independent manner, but was sensitive to inhibition of the stress-activated protein kinase, p38. The activation of IRF3 by viral particles or bacterial membrane components suggests that this signaling pathway might contribute to the evolutionary conserved innate immune response.
Astrocytoma↗
Rapid STAT phosphorylation via the B cell receptor. Modulatory role of CD19.
Engagement of the B cell receptor (BCR) initiates multiple signaling cascades which mediate different biological responses, depending on the stage of B cell differentiation, antigen binding affinity, and duration of stimulation. Aggregation of co-receptors such as CD19 with the antigen receptor has been suggested to modulate the signals necessary for the development and functioning of the humoral immune system. In this study, we demonstrate that engagement of the antigen receptor on peripheral blood B cells, but not naïve splenic B lymphocytes, leads to rapid phosphorylation of signal transducers and activators of transcription 1 (STAT1) on Tyr-701 and Ser-727. Interestingly, phosphorylation on tyrosine diminished with increased stimulation, whereas serine phosphorylation correlated directly with the level of BCR cross-linking. In contrast, phosphorylation of STAT3 occurs exclusively on serine and is sensitive to inhibitors of the PI3-kinase and the ERK1/2 pathways. Finally, we show that co-ligation of CD19 with the BCR results in increased tyrosine phosphorylation of STAT1 relative to BCR cross-linking alone, establishing CD19 as a positive modulator of BCR-mediated STAT activation.
Acute-Phase Proteins↗
[Ten-year experience with heart transplantation (1987-1997)].
OBJECTIVES: Analyze ten years experience with heart transplantation at the Dijon University Hospital and determine which parameters control mid and long term outcome. PATIENTS AND METHODS: One hundred thirty six heart transplantations were performed over a 10 year period (1987-1997) in 118 men and 18 women aged 51-87 years. Heart transplantation was indicated on the basis of the following criteria: ejection fraction *20%, pulmonary arteriole resistance < 6 Wood units, peak oxygen uptake < 14 l/kg/min. The Shumway or anatomic technique was used. The triple immunosuppressive protocol combined corticosteroids, azathioprine and cyclosporin. The same team conducted the post-transplantation follow-up with regular programmed consultations in addition to those requested by the general practitioner, the cardiologist or the patient. Follow-up was oriented according to the clinical situation (blood chemistry, cell counts, cyclosporinemia, search for infection, echocardiography, endomyocardial biopsy, coronarography). RESULTS: Five patients (3.6%) died when still on the waiting list. Absolute emergency transplantation was performed for patients (28.1%) including 8 (5.9%) after circulatory assist. Hospital mortality was 11.7% and late mortality was 16.1%. Actuarial survival was 78% at 1 year, 71% at 5 years and 69% at 10 years. Among the survivors, 94% were taking two, three or even four drugs for hypertension. Cyclosporin levels decreased and creatinine levels increased. Episodes of rejection were minimal: 86.57% of the biopsies were * grade 1 and 4.45% * grade 2. Cytomegalovirus infection was documented and treated in 7.55% of the cases. Incidence of graft coronary artery disease was 3.4% at 1 year, 6.5% at 2 years and 7.9% at 3 years. CONCLUSION: Our follow-up structure where the same small team conducts regular examinations together with our approach to heart transplantation appears to be the main factor leading to the quality results obtained in this series.
Aged↗
Inhibition of B cell receptor-mediated apoptosis by IFN.
IFNs are a family of cytokines that are involved in the regulation of immune and inflammatory responses. Clinical use of IFN-alpha/beta encompasses treatment for a variety of diseases; however, prolonged exposure to IFN-alpha/beta results in elevated levels of autoreactive Abs. In this study, we investigated the potential of IFNs to modulate apoptotic signals in B cells. We demonstrate that IFN-alpha or IFN-beta inhibit Ag receptor-mediated apoptosis in a dose-dependent manner. Inhibition of phosphatidylinositol 3' (PI3)-kinase did not abolish the effect of IFN, indicating that the antiapoptotic mechanism is PI3-kinase- and protein kinase B/Akt-independent. Instead, IFN-alpha and IFN-beta, but not IFN-gamma, significantly increase the levels of the survival protein Bcl-2, and to a lesser extent, Bcl-xL expression. Thus, IFN-alpha/beta-mediated inhibition of B cell Ag receptor-triggered apoptosis may offer a model for the process that leads to the escape of self-reactive B cells from negative selection and consequently results in autoantibody production.
Androstadienes↗
Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine.
Galactose-targeted delivery of macromolecules and drug conjugates to asialoglycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2. Gradient high performance liquid chromatography (HPLC) evaluation of plasma and urine has been combined with 123I-based imaging to show biphasic clearance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), and approximately 30% delivery of the drug to the hepatic region, as determined by planar whole body imaging at 24 h. This patient has a multifocal hepatoma, and single photon emission computed tomography (SPECT) analysis showed a ratio of tumour tissue to normal liver uptake of approximately 1:3, at 24 h. On the basis of this patient, effective hepatic targeting can be achieved following an intravenous dose of 20 mg/m2 doxorubicin as PK2, however the therapeutic usefulness of this targeted drug has yet to be established.
Antibiotics, Antineoplastic↗
[Treatment of generalized pruritus].
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Humans↗
Migratory ichthyosiform dermatosis with type 2 diabetes mellitus and insulin resistance.
BACKGROUND: In addition to the well-defined hereditary primary ichthyoses, many sporadic or less well-defined keratinization disorders with or without systemic manifestations have been reported. Herein we describe ichthyosiform dermatosis associated with type 2 diabetes mellitus. OBSERVATIONS: The patients were members of a large Arab family with heavy consanguinity. Eighteen members were affected with a variously severe scaly disorder. They showed migratory polycyclic keratotic scaly plaques evolving into diffuse generalized scaling or complete remission. Acanthosis nigricans-like lesions were also noted, and there was an association with type 2 diabetes mellitus. A scarcity of intercorneocyte lamellae and reduction in lamellar body contents were observed. CONCLUSIONS: We could not find a report of a similar dermatosis. Furthermore, an association between ichthyosis and diabetes has not been documented. Therefore, we believe that this may constitute a new entity.
Adolescent↗
STIR magnetic resonance imaging: a noninvasive method for detection and follow-up of dermatomyositis.
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Dermatomyositis↗
T cell control of staphylococcal enterotoxin B (SEB) lethal sensitivity in mice: CD4+ CD45RB(bright)/CD4+ CD45RB(dim) balance defines susceptibility to SEB toxicity.
Radiation chimeras, generated by transplantation of SCID bone marrow into C3H/HeJ mice, show lethal susceptibility to staphylococcal enterotoxin B (SEB), thus constituting a valid murine model for SEB shock. This SEB sensitivity is due to the ability of the irradiated host to restore residual T cell populations, since the SCID donor bone marrow is unable to generate T cells. SCID bone marrow transplanted into irradiated nude mice does not generate SEB-sensitive chimeras, as a consequence of the inability of the recipient nude mice to develop mature T cells. Thymectomy of normal recipient mice prior to bone marrow transplantation does not affect the development of susceptibility to SEB, suggesting that postthymic, residual T cells of the host probably mediate this SEB sensitivity. In vivo depletion experiments show that CD4+ T cells are required for the SEB-triggered shock, while CD8+ cells suppress it. A further examination of the T helper subpopulations in the SEB-sensitive mice reveals a prevalence of CD4+ CD45RB(dim) cells over CD4+ CD45RB(bright) cells. This T helper balance was statistically significant when correlated with SEB-induced mortality. Our model provides a possible explanation for the SEB resistance of normal mice: they have a prevalence of CD4+ CD45RB(dim) over CD4+ CD45RB(bright) cells.
Animals↗
Intravenous drug abuse is an indication for antepartum screening for RH alloimmunization. A case report and review of literature.
Intravenous drug abuse is a risk for alloimmunization in pregnancy. One case is presented of a nulliparous Rhesus-negative parturient who shared her Rhesus-positive partner's needles for the injection of heroin; she subsequently developed elevated antepartum anti-D titers despite routine anti-D prophylaxis.
Adult↗
Perinatal outcome in hospital and birth center obstetric care.
OBJECTIVE: Our purpose was to compare birth complications and fetal outcome in hospitals and birth centers. METHOD: We retrospectively compared all 801 deliveries between 1992 and 1994 from two free-standing birth centers against 3271 hospital deliveries in Berlin. The hospital collective was selected according to the same risk criteria of the birth centers. RESULTS: The birth center group had significantly fewer medical interventions, with a similar cesarean section rate (3.0% vs. 4.6%, P = 0.057) and occurrence of severe perineal lesions. The episiotomy rate was significantly higher (P < 0.001) in the clinics for first-time and multiple births. The perinatal mortality was not significantly different ( < 0.1 per 1000). One-minute Apgar scores less than 7 were found significantly more often in the birth center group. CONCLUSION: When birth centers employ thorough risk selection and significant early referral rates to nearby hospitals, there is no evidence of increased maternal or perinatal risk compared to hospital deliveries.
Birthing Centers↗
Toxicity profile of interferon alfa-2b in children: A prospective evaluation.
The toxicity of interferon (IFN) alfa-2b therapy was prospectively evaluated in 53 children treated from 1991 to 1996 in 2 successive studies of IFN alfa therapy for severe hemangiomas at Sainte-Justine Hospital. Toxicity was generally mild and transient, with grade 1 toxicity occurring in 100% of patients, grade 2 toxicity in 89%, grade 3 toxicity in 58%, and grade 4 toxicity in 17%. Ten of 43 patients available for evaluation had an abnormal neurologic examination. Severe neurotoxicity in the form of spastic diplegia occurred in one patient. In conclusion, IFN alfa therapy is generally well tolerated in children. However, it may rarely be associated with severe toxicity and must be used with caution.
Antineoplastic Agents↗
Adverse cutaneous reactions to ticlopidine in patients with coronary stents.
A prospective study was carried out to assess the occurrence and character of adverse cutaneous reactions in patients receiving ticlopidine hydrochloride to prevent subacute thrombosis after having undergone placement of coronary stents. During a 1-year period such patients were requested to report any adverse cutaneous reactions, and those with skin reactions were referred for dermatological evaluation. Among the 136 patients who underwent stent placement by one of the authors, 20 were referred for dermatological evaluation. Of these, 16 (11.8%) fit the case definition of ticlopidine-associated cutaneous reactions. In the first 8 consecutive patients ticlopidine was withdrawn (in 2 of these a rechallenge test was later performed); in the next 8 patients ticlopidine was not discontinued before completion of the intended 4-week period of treatment. Patients remained under weekly follow-up and underwent a weekly blood count. Skin biopsies were obtained in 5 patients with different types of eruptions. The skin reactions appeared from 2 to 21 days after commencement of ticlopidine (mean, 10 days), lasting from 2 to 30 days (mean, 5 days). Only 3 patients had other adverse effects: neutropenia in 1 and abdominal pain and nausea in 2. The most common presentations were urticaria, pruritus, and maculopapular eruption. In 3 patients there were previously unreported reactions: fixed drug eruption, erythromelalgia-like eruption, and erythema multiforme-like eruption. Of note was the rapid clearing of the skin eruption in most cases even when the drug was not withdrawn. It was concluded that adverse cutaneous reactions are relatively common in association with ticlopidine treatment but that serious reactions are rare and the disappearance of the signs and symptoms is rapid, suggesting that discontinuation of the drug is not usually imperative.
Aged↗
Effect of colchicine in the subcorneal pustular dermatosis type of IgA pemphigus.
BACKGROUND: IgA pemphigus of the subcorneal pustular dermatosis (SPD) type is characterized by subcorneal acantholysis and by an abundance of neutrophils, making colchicine a reasonable pharmacologic option for treatment. OBJECTIVE: We attempted to determine the efficacy of colchicine in the treatment of SPD-type IgA pemphigus. METHODS: Two patients with SPD-type IgA pemphigus were treated with colchicine 1.5 mg/day as monotherapy. RESULTS: A sustained clinical response was achieved within 2 to 3 weeks of therapy. Relapses were noted each time colchicine was stopped. CONCLUSION: Colchicine should be considered in the treatment of SPD-type IgA pemphigus.
Colchicine↗
Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients.
OBJECTIVE: To assess risk factors for mortality in cardiac surgical adult patients as part of a study to develop a European System for Cardiac Operative Risk Evaluation (EuroSCORE). METHODS: From September to November 1995, information on risk factors and mortality was collected for 19030 consecutive adult patients undergoing cardiac surgery under cardiopulmonary bypass in 128 surgical centres in eight European states. Data were collected for 68 preoperative and 29 operative risk factors proven or believed to influence hospital mortality. The relationship between risk factors and outcome was assessed by univariate and logistic regression analysis. RESULTS: Mean age (+/- standard deviation) was 62.5+/-10.7 (range 17-94 years) and 28% were female. Mean body mass index was 26.3+/-3.9. The incidence of common risk factors was as follows: hypertension 43.6%, diabetes 16.7%, extracardiac arteriopathy 2.9%, chronic renal failure 3.5%, chronic pulmonary disease 3.9%, previous cardiac surgery 7.3% and impaired left ventricular function 31.4%. Isolated coronary surgery accounted for 63.6% of all procedures, and 29.8% of patients had valve operations. Overall hospital mortality was 4.8%. Coronary surgery mortality was 3.4% In the absence of any identifiable risk factors, mortality was 0.4% for coronary surgery, 1% for mitral valve surgery, 1.1% for aortic valve surgery and 0% for atrial septal defect repair. The following risk factors were associated with increased mortality: age (P = 0.001), female gender (P = 0.001), serum creatinine (P = 0.001), extracardiac arteriopathy (P = 0.001), chronic airway disease (P = 0.006), severe neurological dysfunction (P = 0.001), previous cardiac surgery (P = 0.001), recent myocardial infarction (P = 0.001), left ventricular ejection fraction (P = 0.001), chronic congestive cardiac failure (P = 0.001), pulmonary hypertension (P = 0.001), active endocarditis (P = 0.001), unstable angina (P = 0.001), procedure urgency (P = 0.001), critical preoperative condition (P = 0.001) ventricular septal rupture (P = 0.002), noncoronary surgery (P = 0.001), thoracic aortic surgery (P = 0.001). CONCLUSION: A number of risk factors contribute to cardiac surgical mortality in Europe. This information can be used to develop a risk stratification system for the prediction of hospital mortality and the assessment of quality of care.
Adolescent↗
Evidence for the cofactor role of human T-cell lymphotropic virus type 1 in mycosis fungoides and Sézary syndrome.
The aetiology of mycosis fungoides (MF) and Sézary syndrome (SS) is unknown. A pathogenic role for the human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. We used an animal model to test the possibility that peripheral blood mononuclear cells (PBMC) obtained from MF patients harbour the HTLV-1 virus which may be infective. The polymerase chain reaction (PCR) was used to detect HTLV-1 proviral DNA sequences in PBMC of 27 MF patients and one SS patient of non-Iranian origin. Positive results were found in six of the patients. Twelve of the 28 patients tested by Western blot showed HTLV-1 antibodies. Twenty-eight immunosuppressed inbred Fisher F344 rats were inoculated intravenously with cultures of PBMC obtained from the 28 patients. Eight of these 28 rats showed antibodies to HTLV-1 while the proviral genome was demonstrated in the blood of only two of the rats. PBMC from two MF patients, in spite of showing negative results for the proviral genome by PCR, still induced HTLV-1 antibody formation in the F344 rat model. None of 10 control rats inoculated with normal donor PBMC showed antibodies to HTLV-1, nor the proviral genome. The present study suggests that HTLV-1 plays a cofactor role in MF/SS patients.
Adoptive Transfer↗