Education and bonhomie at Jalandhar. A report on XVII S.N.A. Biennial Conference.
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Education, Nursing↗
Biomedical subjects
M David
Publications and source records attributed to M David.
[The influence of sociodemographic and familial factors on the therapeutic evolution of heroin addicts in a program of staged combined treatment].
In this study the authors evaluate the history of drug abuse, the familial and sociodemographic influence on the clinical evolution of 74 heroin-addicts, admitted sequentially to a therapeutic drug-free program named Sequential Combined Treatment (SCT), based on family and individual counselling, with a daily administration of naltrexone and with regular evaluation of drug abstinence, based on urinary analysis collected by family members. The enrollment rate recorded was 76%, and the participation rates during the course of the program were 88% after 3 months of administering the antagonist, 57% after 6 months, 47% after 9 months and 46% at the end of the 12th month. The results showed that age and previous scholarship levels, as well as parental or marital conflicts were significant predictors of over the subjects' total participation time in the program. The heroin-addicts with higher levels of scholarship or with drug abuse problems with other family members had more relapses during the treatment. No differences were found in the clinical variables of the therapeutic evolution among drug-addicts belonging to nuclear or enlarged family structures and single-parent or reconstructed family structures, which suggests that Sequential Combined Treatment (SCT) seems to have sufficiently similar results independently of the type of family structure to which they belong.
Adolescent↗
[The bases and indications for the staged combined treatment of heroin addicts as outpatients].
Combined and staged treatment is a new clinical methodology for the orientation of drug addiction cases within families. This methodology resorts to several techniques in a combined way, such as: family therapy and counselling; the use of psychopharmacology and opioide antagonists; as well as individual and group psycho-therapeutics. These are all linked to a personal psycho-social rehabilitation program. This treatment is based on family accessibility and therapeutic community programs. The authors review different contributions and the evolution of different therapeutic modalities. Finally they propose a list for inductions and another for the formal contra-indications for this kind of treatment.
Ambulatory Care↗
The SH2 domain-containing tyrosine phosphatase PTP1D is required for interferon alpha/beta-induced gene expression.
Interferons (IFNs) induce early response genes by stimulating Janus family (Jak) tyrosine kinases, leading to tyrosine phosphorylation of Stat (signal transducer and activator of transcription) proteins. Previous studies demonstrated that a protein-tyrosine phosphatase (PTP) is required for activation of the ISGF3 transcription complex by IFNalpha/beta, but the specific PTP responsible remained unidentified. We now show that the SH2 domain containing tyrosine phosphatase PTP1D (also designated as SHPTP2, SHPTP3, PTP2C, or Syp) is constitutively associated with the IFNalpha/beta receptor and becomes tyrosine-phosphorylated in response to ligand. Furthermore, transient expression of a phosphatase-inactive mutant or the COOH-terminal SH2 domain of PTP1D causes a dominant negative effect on IFNalpha/beta-induced early response gene expression. These results provide strong evidence that PTP1D functions as a positive regulator of the IFNalpha/beta-induced Jak/Stat signal transduction pathway.
Base Sequence↗
Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis.
BACKGROUND: Atherosclerotic lesions are heterogeneous and prognosis cannot easily be predicted, even with intracoronary ultrasound and angioscopy. Serial angiographic and necropsy studies suggest that the risk of plaque rupture correlates only weakly with the degree of stenosis. Most ruptured plaques are characterised by a large pool of cholesterol or necrotic debris and a thin fibrous cap with a dense infiltration of macrophages. The release of matrix-digesting enzymes by these cells is thought to contribute to plaque rupture. Other thromboses are found on non-ruptured but inflamed plaque surfaces. We postulated that both types of thrombotic events may be predicted by heat released by activated macrophages either on the plaque surface or under a thin cap. METHODS: To test the hypothesis, we measured the intimal surface temperatures at 20 sites in each of 50 samples of carotid artery taken at endarterectomy from 48 patients. The living samples were probed with a thermistor (24-gauge needle-tip; accuracy 0.1 degree C; time contrast 0.15 s). The tissues were then fixed and stained. FINDINGS: Plaques showed several regions in which the surface temperatures varied reproducibly by 0.2-0.3 degrees C, but 37% of plaques had substantially warmer regions (0.4-2.2 degrees C). Points with substantially different temperatures could not be distinguished from one another by the naked eye; such points could also be very close to one another (< 1 mm apart). Temperature correlated positively with cell density (r = 0.68, p = 0.0001) and inversely with the distance of the cell clusters from the luminal surface (r = -0.38, p = 0.0006). Most cells were macrophages. Infrared thermographic images also revealed heterogeneity in temperature among the plaques. INTERPRETATION: Living atherosclerotic plaques show thermal heterogeneity, which raises the possibility that an infrared catheter or other techniques that can localise heat or metabolic activity might be able to identify plaques at high risk of rupture or thrombosis.
Carotid Arteries↗
STAT activation by epidermal growth factor (EGF) and amphiregulin. Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1.
The epidermal growth factor (EGF) receptor activates several signaling cascades in response to the ligands EGF and amphiregulin (AR). One of these signaling events involves the tyrosine phosphorylation of STATs (signal transducers and activators of transcription), a process believed to require the activation of a tyrosine kinase of the JAK family. In this report we demonstrate that EGF- and AR-induced STAT activation requires the intrinsic kinase activity of the receptor but not the presence of Jak1. We show that both wild type (WT) and truncated EGF receptors lacking all autophosphorylation sites activate STAT 1, 3, and 5 in response to either EGF or AR. Furthermore, relative to cells expressing WT receptor, ligand-induced tyrosine phosphorylation of the STATs was enhanced in cells expressing only the truncated receptor. These results provide the first evidence that (i) EGF receptor-mediated STAT activation occurs in a Jak1-independent manner, (ii) the intrinsic tyrosine kinase activity of the receptor is essential for STAT activation, and (iii) tyrosine phosphorylation sites within the EGF receptor are not required for STAT activation.
Amphiregulin↗
[Advances in surgery for carotid stenosis. 900 operations (1983-1994)].
OBJECTIVES: To evaluate morbidity and mortality in carotid endarterectomy in a personal series. METHODS: Nine hundred endartectomies were performed from 1983 to 1994. All patients had > 70% carotid narrowing. Five hundred five patients underwent without preoperative angiography. RESULTS: Outcome was analyzed for 3 periods showing decreasing mortality from 4.56% in 1983-86 to 0.67% in 1990-1994. CONCLUSION: The reduction in morbidity and mortality resulted from the combined effects of pre-, per-, and post-operative care including noninvasive preoperative diagnosis of internal carotid artery stenosis using ultrasound duplex and surgery without previous angiography, delayed surgery in case of recent prolonged hemispheric deficit or of ischemic defect detected on computed tomography (CT) or magnetic resonance imaging (MRI), cerebral evaluation with CT-scan or MRI the day before operation, surgery under locoregional anesthesia, monitoring of arm arterial blood pressure during the first 24 hours following surgery.
Aged↗
Use of electrospray ionization liquid chromatography-mass spectrometry to study the role of CYP2D6 in the in vitro metabolism of 5-hydroxytryptamine receptor antagonists.
An electrospray ionization liquid chromatographic-mass spectrometric (ESI-LC-MS) method has been developed to study the involvement of the cytochrome P450 isoenzyme CYP2D6 in the in vitro metabolism of the indole containing 5-hydroxytryptamine (5-HT(3)++) receptor antagonists tropisetron, ondansetron and dolasetron in human liver microsomes. Compounds were eluted using linear gradients of acetonitrile-20 mM ammonium acetate, solvent A, (10:90, v/v) (pH 6.0) and solvent B, (60:40, v/v) (pH 6.0) and a Nucleosil C(4) column. Microsomal incubations were analysed using selected ion monitoring of the molecular ion of parent drug and the molecular ion of hydroxylated metabolites. The involvement of CYP2D6 in drug metabolism was assessed by inhibition studies using quinidine (5 mu M), a specific inhibitor of human CYP2D6, as well as by incubating compounds with microsomes prepared from cells transfected with cDNA encoding human CYP2D6. Results showed that the oxidation of all three compounds involved CYP2D6, but only that of tropisetron was inhibited by over 90% in the presence of quinidine. The present method can be applied to pre-clinical compounds, at an early stage of drug discovery, to assess the involvement of CYP2D6 in their metabolism and to screen for those compounds where CYP2D6 is the only isoenzyme implicated in the formation of major metabolites.
Chromatography, Liquid↗
Allograft and xenograft rejection in C3H/SCID mice. A new model for the study of non-T cell graft rejection mechanisms.
Comparative cell transfer experiments have revealed that, despite their equal immune deficiency, C3H/SCID mice were markedly inferior compared with C.B-17/SCID mice in their ability to accept allogeneic and xenogeneic grafts. Allogeneic C.B-17/SCID bone marrow cells were engrafted poorly compared with syngeneic C3H/SCID when transplanted into C3H/SCID recipients, whereas cells of both strains were equally well engrafted into C.B-17/SCID mice. C.B-17/SCID mice were much more permissive for outgrowth of human Burkitt lymphoma (Raji), as well as for Epstein-Barr virus lymphoma development after transplantation of human peripheral blood lymphocytes. Human skin grafts were accepted by the C.B-17/SCID mice but were promptly rejected by the C3H/SCID mice. The resistance to human RaJi cells could be adoptively transferred by infusion of C3H/SCID splenocytes into C.B-17/SCID mice. Because the C.B-17/SCID and C3H/SCID mice equally lack both T and B lymphocytes, the latter may provide a relevant model for studies of non-T mechanisms of allograft or xenograft rejection.
Animals↗
Activation of protein kinase A inhibits interferon induction of the Jak/Stat pathway in U266 cells.
Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation of the Stat transcription factors and is mediated by the Jak family of tyrosine kinases. Recent evidence suggests that ERK2 serine/threonine kinase modulates the IFN-stimulated Jak/Stat pathway. In this report we show that in the myeloma cell line U266 protein kinase A specifically interacts with the cytoplasmic domain of the IFNalpha/beta receptor. Treatment of cells with the adenylate cyclase activator forskolin inhibits IFNbeta-, IFNgamma-, and hydrogen peroxide/vanadate-induced formation of complexes that bind to enhancers known to stimulate the expression of IFN-regulated genes. Immunoprecipitations followed by anti-phosphotyrosine immunoblots indicate that tyrosine phosphorylation of the alpha chain of the IFNalpha/beta receptor, Jak1, Tyk2, as well as Stat1 and Stat2 is reduced as a consequence of incubation of cells with forskolin. In contrast, dideoxyforskolin, which fails to activate adenylate cyclase, has no effect on IFN induction of the Jak/Stat pathway. These results indicate a novel regulatory mechanism by which protein kinase A can modulate the Jak/Stat signaling cascade.
Adenylyl Cyclases↗
Preassociation of STAT1 with STAT2 and STAT3 in separate signalling complexes prior to cytokine stimulation.
A variety of cytokines and growth factors act through an induction of gene expression mediated by a family of latent transcription factors called STAT (signal transducers and activators of transcription) proteins. Ligand-induced tyrosine phosphorylation of the STATs promotes their homodimer and heterodimer formation and subsequent nuclear translocation. We demonstrate here that STAT protein heterocomplexes exist prior to cytokine treatment. When unstimulated HeLa cells are ruptured in hypotonic buffer without salt or detergent, immunoadsorption of either STAT1 or STAT2 from the resulting cytosol yields coimmunoadsorption of the other STAT protein. Similarly, STAT1-STAT3 heterocomplexes are coimmunoadsorbed from hypotonic cytosol. STAT1 and STAT2 or STAT1 and STAT3 translated in reticulocyte lysate spontaneously form heterocomplexes when the translation lysates are mixed at 0 degrees C. Our data suggest that interferon-alpha /beta-induced tyrosine phosphorylation increases the stability of a preexisting, latent, STAT1-STAT2 signaling complex. Newly translated STAT1 binds in equilibrium fashion to STAT2 and STAT3, but we show that STAT2 and STAT3 exist in separate heterocomplexes with STAT1, consistent with a model in which STAT1 contains a common binding site for other STAT proteins.
3T3 Cells↗
Maternal serum markers levels in consecutive pregnancies: a possible genetic predisposition to abnormal levels.
The study comprised 2,361 women, each with two consecutive normal uncomplicated pregnancies screened at 15-20 weeks gestation for maternal serum alpha-fetoprotein levels (AFP). In 1,816 of these women, maternal serum human chorionic gonadotropin (hCG) levels were tested as well. The proportion of women who had a second high AFP level (> or = 2.0 MOM) in their subsequent pregnancy was 6.5-fold higher as compared with the proportion of women who had normal levels of AFP in their first tested pregnancy. The relative chance of having a second positive result of a low level of AFP (AFP < or = 0.5 MOM) in subsequent pregnancies was 3.8-fold higher. The relative chances of having a second positive result of high or low levels of hCG were 3.9- and 2.2-fold higher, respectively. It is concluded that there is a predisposition for abnormal levels of serum markers that is influenced by genetic and/or environmental factors. Therefore it is suggested that the individual's risk of having a Down syndrome baby, or other adverse pregnancy outcome that is derived from the serum markers' levels, should be adjusted taking into account unexplained high or low levels in previous pregnancies. A screening policy is suggested which is designed to yield a lower false-positive rate without affecting the detection rate of abnormal pregnancies. More data are needed before an accurate adjustment based on previous results can be made.
Chorionic Gonadotropin↗
Hyperactive polymorphonuclear leucocytes migration in patients with Familial Mediterranean Fever.
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Adult↗
Human-->mouse radiation chimera do not develop Epstein-Barr virus lymphoma.
It has been shown that engraftment of human peripheral blood lymphocytes (PBL) from Epstein-Barr virus (EBV) seropositive donors in C.B-17/SCID mice is associated with a high incidence of human B cell tumors. More recently, we described a new approach enabling engraftment of human PBL in normal strains of mice or rats receiving lethal split-dose radiation and radioprotected with SCID bone marrow. We now demonstrate that, in contrast to SCID recipients of human PBL, Balb/c and C3H/HeJ recipients of 50-100 x 10(6) human PBL did not develop any EBV lymphoma during a 7-month follow-up period, but were successfully engrafted with human B and T cells. On the other hand, lymphoma developed in 90% of the C.B-17/SCID mice infused with 70 x 10(6) human PBL from the same donor. Likewise, 36% of beige/nude/xid (BNX) mice, exposed to 12 Gy TBI, radioprotected with SCID bone marrow and then transplanted with human PBL developed lymphoma. Similar results were obtained when different strains were infused with PBL of the same donor. Immunohistochemical analysis indicated that the tumor cells were of human B cell origin and expressed the EBV-encoded latent membrane protein-1 and nuclear antigen 2. While further studies are required to understand the mechanisms which suppressed outgrowth of EBV lymphoma in human --> mouse radiation chimera, compared to human --> C.B-17/SCID or human --> BNX chimera, this marked resistance offers new possibilities for transplantation of hematopoietic tissues or cells from EBV-positive donors.
Animals↗
Anticoagulation without catheter removal in children with catheter-related central vein thrombosis.
Catheter-related central venous thrombosis is a serious and common problem among children. The traditional management has been anticoagulation and early catheter removal. Unfortunately, many patients require a new catheter, which is associated with complications that include possible further thrombosis. Although others have used thrombolytic agents in attempts to avoid catheter removal, the authors of the present study believe that the associated complications occur too frequently and are too serious. They have had success with standard anticoagulation in a limited number of patients. Between February 1991 and April 1994, 17 patients (6 weeks to 19 years of age) were treated for catheter-related deep venous thrombosis. Eight patients underwent early catheter removal accompanied by anticoagulation; two of them had intrinsic catheter problems that necessitated removal, and one had hemophilia. Nine others received anticoagulation without catheter removal. Of these, one required catheter removal after 10 days heparin administration failed to diminish the thrombosis. Another patient responded well to anticoagulation but required catheter removal several weeks later because of catheter-site infection. The other seven patients responded well to anticoagulation, and their catheters were retained. For patients with a functional catheter essential to their care, anticoagulation may safely prevent catheter removal.
Adolescent↗
Erythromelanosis follicularis faciei in women.
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Dermatitis, Exfoliative↗
Treatment of Candida nail infection with terbinafine.
BACKGROUND: Terbinafine is a highly potent drug against dermatophytes. Data regarding its effectiveness against Candida species are few and variable. OBJECTIVE: Our purpose was to evaluate the efficacy and safety of oral terbinafine in patients with Candida nail infection. METHODS: In an open-label uncontrolled study, 20 patients completed 16 weeks of treatment with terbinafine, 250 mg/day, and an additional 8 weeks with placebo. Efficacy was assessed clinically and mycologically at weeks 0 (baseline), 4, 8, 16, 24, 36, and 48. Routine laboratory studies were performed at baseline and weeks 4, 8, and 16. RESULTS: At the end of the trial 60% of target nails were cured clinically and mycologically; in 10% there was mycologic cure with residual clinical signs, in 25% a moderate improvement (> 50%), and failure in only 5% (one patient). Most nails were infected by Candida parapsilosis. Two of 28 patients showed mild reversible elevation of liver enzymes 1 month after initiation of terbinafine treatment. CONCLUSION: The administration of terbinafine for 16 weeks is effective in the treatment of Candida nail infection. Liver enzyme values should be determined during the first month of treatment.
Administration, Oral↗
In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement of the tumour necrosis factor (TNF) receptor.
Following engraftment of human involved psoriatic skin to nude mice there is a partial normalization of pathology associated with a loss of inflammatory leucocytes. However, the epidermis remains hyperproliferative, which may reflect a primary defect. The roles of TNF-alpha, IL-1 and IL-6 in epidermal hyperproliferation of grafted psoriatic lesions were investigated. Before and after treatment, grafts were analysed to determine epidermal thickness and labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e. p55 by keratinocytes; p75 by epidermal dendritic cells) were identified throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells were found in grafts following a course of TNF-alpha, IL-6 or IL-1 treatment. The p55 form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-alpha or IL-6. HLA-DR and ICAM-1 were also expressed in these grafts. TNF-alpha, anti-IL-1, and anti-IL-6 treatment induced a marked decrease in the epidermal thickness and LI of psoriatic graft tissue, correcting the hyperproliferation associated with psoriatic epidermis. Supraphysiological levels of TNF-alpha may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.
Animals↗