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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 127 records · Page 7Linked to original sources
PubMed1997

T-lymphocyte dependence of psoriatic pathology in human psoriatic skin grafted to SCID mice.

Considerable indirect evidence suggests that T lymphocytes have a role in the pathogenesis of psoriasis. The goal of this study was to directly test the ability of T cells to maintain psoriasis pathology. Psoriatic skin was transplanted onto SCID mice, which were then injected with autologous T cells. T cells were cultured from either psoriatic skin lesions or peripheral blood and injected intradermally or intravenously. Control SCID mice transplanted with psoriasis grafts were not injected with T cells. After 10 wk, control psoriatic skin grafts not injected with T cells lost many of the features of psoriasis. Injection of peripheral blood T cells was not able to maintain these psoriatic features. In contrast, the injection of T cells derived from psoriatic skin was able to maintain the psoriatic phenotype. Psoriatic features that were maintained included epidermal thickness and labeling index and expression of HLA-DR, involucrin, and ICAM-1, as well as loss of expression of filaggrin. Injection of skin infiltrating T cells into skin of normal donors on SCID mice did not induce changes of psoriasis. The ability of T cells from lesional skin, but not peripheral blood, to maintain psoriasis suggests that psoriasis is mediated by an autoantigen reactive T cell, which is present at a higher frequency in the psoriatic lesion.

Adoptive Transfer↗
PubMed1997

Lupus miliaris disseminatus faciei--the DNA of Mycobacterium tuberculosis is not detectable in active lesions by polymerase chain reaction.

There has been a controversy as to the origin of lupus miliaris disseminatus faciei (LMDF). It was originally thought to be associated with tuberculosis, due to its histopathological similarity. Recently, this association has been doubted, although there remain reported cases of LMDF associated with Mycobacterium tuberculosis. Three patients with the clinical and histopathological features of LMDF are described. Skin from these patients was analysed by polymerase chain reaction (PCR) using two different oligoprimers for the detection of 123 bp and 165 bp DNA fragments specific for M. tuberculosis complex. With these two PCR systems, no M. tuberculosis DNA was detected in any of the LMDF patients. It was present in all positive controls and absent in all negative controls. In this study we could not demonstrate an association between LMDF and tuberculosis.

Adolescent↗
PubMed1997

Beta interferon and oncostatin M activate Raf-1 and mitogen-activated protein kinase through a JAK1-dependent pathway.

Activation of early response genes by interferons (IFNs) and other cytokines requires tyrosine phosphorylation of a family of transcription factors termed signal transducers and activators of transcription (Stats). The Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) is required for cytokine-induced tyrosine phosphorylation and dimerization of the Stat proteins. In order for IFNs to stimulate maximal expression of Stat1alpha-regulated genes, phosphorylation of a serine residue in the carboxy terminus by mitogen-activated protein kinase (MAPK) is also required. In HeLa cells, both IFN-beta and oncostatin M (OSM) stimulated MAPK and Raf-1 enzyme activity, in addition to Stat1 and Stat3 tyrosine phosphorylation. OSM stimulation of Raf-1 correlated with GTP loading of Ras, whereas IFN-beta activation of Raf-1 was Ras independent. IFN-beta- and OSM-induced Raf-1 activity could be coimmunoprecipitated with either Jak1 or Tyk2. Furthermore, HeLa cells lacking Jak1 displayed no activation of STAT1alpha, STAT3, and Raf-1 by IFN-beta or OSM and also demonstrated no increase in the relative level of GTP-bound p21ras in response to OSM. The requirement for Jak1 for IFN-beta- and OSM-induced activation of Raf-1 was also seen in Jak1-deficient U4A fibrosarcoma cells. Interestingly, basal MAPK, but not Raf-1, activity was constitutively enhanced in Jak1-deficient HeLa cells. Transient expression of Jak1 in both Jak-deficient HeLa cells and U4A cells reconstituted the ability of IFN-beta and OSM to activate Raf-1 and decreased the basal activity of MAPK, while expression of a kinase-inactive form of the protein showed no effect. Moreover, U4A cells selected for stable expression of Jak1, or COS cells transiently expressing Jak1 or Tyk2 but not Jak3, exhibited enhanced Raf-1 activity. Therefore, it appears that Jak1 is required for Raf-1 activation by both IFN-beta and OSM. These results provide evidence for a link between the Jaks and the Raf/MAPK signaling pathways.

Animals↗
PubMed1997

Peripherally inserted central catheters in infants and children.

PURPOSE: To determine prospectively the feasibility, complications, and mid- and long-term advantages of peripheral insertion of central catheters in infants and children. MATERIALS AND METHODS: During a 15-month period between March 1995 and June 1996, a total of 285 catheter placement attempts were made to peripherally insert central catheters in 183 pediatric patients (89 boys, 94 girls). Phlebographic guidance was used, and the catheters were inserted below the elbow in 99% of cases. Catheter insertion was indicated for prolonged antibiotic therapy in 108 patients (158 catheter placement attempts), hematologic or oncologic care in 24 patients (40 attempts), total parenteral nutrition in 16 patients (46 attempts), and venous access for fluid or blood in 35 patients (41 attempts). The success rate and complications were recorded along with the indication, patient age, and duration of catheter placement. RESULTS: One hundred fifty-two of 158 (96%) catheter placement attempts were successful in outpatients (n = 108), 124 of 127 (98%) in hospitalized patients (n = 75), and 70 of 73 (96%) in patients aged less than 1 year. Infection and pericatheter venous thrombosis were the main complications and were seen in 17 of 276 (6%) and one of 276 (0.3%) catheter placement attempts, respectively. Catheter occlusion occurred in 23 of 276 (8%) catheter placement attempts. CONCLUSION: Peripheral insertion of central catheters was highly feasible in infants and children with this protocol. Such catheters were well tolerated in the pediatric population with a low frequency of complications.

Catheterization, Central Venous↗
PubMed1997

Identification of a large-scale mitochondrial deoxyribonucleic acid deletion in endocrinopathies and deafness: report of two unrelated cases with diabetes mellitus and adrenal insufficiency, respectively.

In recent years, a broad variety of chronic diseases have been related to different mitochondrial DNA (mtDNA) rearrangements. We have investigated two 16-yr-old unrelated girls with unexplained endocrine disorders for a mtDNA mutation. One initially presented with an adrenal crisis at the age of 4 yr. Complete adrenal insufficiency for nearly 15 yr was the main clinical manifestation, along with insiduous growth retardation and sensorineural hearing loss since age 6. The other girl presented with ketoacidosis at the age of 15 yr. She exhibited incomplete deafness since age 6 and poor growth. In both patients, brain magnetic resonance imaging abnormalities and raised cerebrospinal fluid protein concentration indicated mild leucodystrophy. Biopsy of skeletal muscle showed a mitochondrial dysfunction; molecular analysis using a PCR screening procedure revealed a 7.4 kb deletion of the mtDNA in skeletal muscle but not in leucocytes. Direct sequence analysis of the junctional regions showed that the deletion spanned 7.436 kb (nucleotide 8649 to nucleotide 16084). The relative amount of deleted mtDNA estimated by Southern blot analysis was 25 and 15%, respectively. No deletion was present in leukocytes obtained from the asymptomatic mothers. The presence of the same mutation in different patients with various endocrine conditions supports the view that the 7.4 kb mtDNA deletion should be considered as one of the candidate causes for phenotypically uncommon cases of endocrinopathies, specially in children with deafness. This is the first report of a mitochondrial disease with primary adrenocortical insufficiency as the clinical onset.

Adolescent↗
PubMed1997

[Unexplained pulmonary edema: demonstration of obstruction to pulmonary venous return by transesophageal echocardiography. Apropos of 4 cases].

The usual causes of pulmonary edema are left ventricular dysfunction, mitral valve disease or left atrial myxoma. Obstruction to pulmonary venous drainage is a rare and unrecognised diagnosis which should be considered when the usual investigations are unproductive. The authors report four cases in which transesophageal echocardiography showed pulmonary edema to be due to compression of one or more pulmonary veins by a mediastinal mass (2 cases), by the false lumen of dissection of the aorta (1 case) and postoperative stenosis of the pulmonary veins (1 case). These cases underline the diagnostic value of this technique which rapidly provides diagnostic information with privileged visualisation of the pulmonary veins and abnormalities of acceleration of blood velocities in the Doppler mode due to obstruction.

Aged↗
PubMed1997

[Intrabronchial migration and extraction of a fragment of an Accufix J-shaped atrial pacing catheter].

The authors report a case of exteriorisation and migration of a fragment of a J-shaped atrial Accufix Telectronix (Stimarec Class IV) responsible for a bronchial penetration without clinical repercussion. A systematic control chest X-ray detected this complication. The position of the metallic fragment was determined by chest CT scan and bronchial fibroscopy between the inferior right lobar bronches and artery confirming bronchial perforation. Rigid bronchoscopy with direct visualisation enabled extraction of the foreign body without complications.

Bronchi↗
PubMed1997

Pattern of superoxide dismutase enzymatic activity and RNA changes in rat heart ventricles after myocardial infarction.

A multiplex reverse transcription polymerase chain reaction assay was designed to measure manganese superoxide dismutase (MnSOD) and CuZnSOD mRNAs in the left and right ventricles of rat hearts after myocardial infarction induced by occlusion of the left coronary artery. These data were compared with changes in enzymatic activities. In the left ventricle, Mn-SOD RNA increased significantly at 6 hours, peaked at 12 hours (490 +/- 38 arbitrary units), and progressively decreased (127 +/- 21 arbitrary units at 48 hours). In contrast, there was a steady accumulation of transcripts in the right ventricle up to 48 hours. In both ventricles, the changes in the MnSOD mRNA and protein content were not associated with proportional variations in enzymatic activity. There was no characteristic alteration of the CuZnSOD system in either ventricle over the 48-hour period. These results demonstrate that infarction selectively activates the MnSOD gene in the viable myocardium of both ventricles. They suggest that MnSOD may be involved in the adaptive response of myocytes to the overloading stress.

Animals↗
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

[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↗
PubMed1996

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↗