p53-dependent impairment of T-cell proliferation in FADD dominant-negative transgenic mice.

Members of the tumour necrosis factor (TNF) receptor family exert pleiotropic effects and can trigger both apoptosis and proliferation [1]. In their cytoplasmic region, some of these receptors share a conserved sequence motif - the 'death domain' - which is required for transduction of the apoptotic signal by recruiting other death-domain-containing adaptor molecules like the Fas-associated protein FADD/MORT1 or the TNF receptor-associated protein TRADD [2-4]. FADD links the receptor signal to the activation of the caspase family of cysteine proteases [5,6].

A dominant-negative mutant of the Rab5 GTPase enhances T cell signaling by interfering with TCR down-modulation in transgenic mice.

TCR triggering results in the down-modulation of engaged receptors by endocytosis. As a result of this process, Ag-binding sites are depleted from the surface and signaling responses should be attenuated. To test the importance of TCR down-regulation on T cell signaling, we generated mice expressing a dominant-negative form of Rab5 (Rab5N133I) in T cells.

Expression and upregulation of microtubule-associated protein 1B in cultured retinal pigment epithelial cells.

Purpose: During routine cell culture and under pathologic conditions, human retinal pigment epithelial (RPE) cells lose epithelial characteristics and change their morphology. In this study, changes in gene expression in RPE cells of different generations were evaluated by polymerase-chain-reaction-based differential display mRNA analysis (DD-RT-PCR).

Methods: Total RNA was prepared from freshly isolated and cultured human RPE cells of passages P0 and P3 and was subjected to DD-RT-PCR.

Gene structure, cDNA sequence, and expression of murine Bak, a proapoptotic Bcl-2 family member.

To facilitate the creation of Bak knockout mice and the further analysis of this Bcl-2 family member, we have isolated and sequenced the complete mouse Bak cDNA. The cDNA is 2 kb long and shares an overall nucleotide identity to the human Bak cDNA of 62%. The mouse Bak protein is 208 amino acids long with a predicted molecular weight of 23 kDa.

Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired differentiation.

Thy-1, a single variable-like immunoglobulin superfamily domain anchored in the plasma membrane by a glycosyl phosphaditylinositol tail [1], is a major surface glycoprotein in adult mammalian neurons and rodent thymocytes [2]; the function of Thy-1 has remained enigmatic since its discovery [3]. Studies in vitro have implicated Thy-1 in homotypic and heterotypic cell-cell interactions [2,4]. Ligation of Thy-1 initiates transmembrane signaling pathways that lead to diverse physiological outcomes in different cells [2,5-7].

Iontophoresis of bases, nucleosides, and nucleotides.

Purpose: To investigate whether transdermal iontophoresis may be potentially useful for delivery of oligonucleotide drugs, the electrotransport of representative bases (uracil and adenine), nucleosides (uridine and adenosine) and nucleotides (AMP, ATP, GTP and imido-GTP) across mammalian skin in vitro has been considered.

Methods: While the passive permeability of all compounds investigated (from 1 mM solutions at pH 7.4) was very low, the application of constant current iontophoresis (0.

Basic fibroblast growth factor mRNA, bFGF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders (PVR and PDR).

Basic fibroblast growth factor (bFGF) has been shown to be involved in epiretinal membrane formation in proliferative vitreoretinal disorders. However, up to now, little knowledge exists; as to the actual cellular source of this potent mitogen. We examined 20 epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) (n = 12) and proliferative vitreoretinopathy (PVR) (n = 8) for the presence of bFGF peptide, fibroblast growth factor receptor-1 (FGFR-1) and bFGF messenger ribonucleic acid (mRNA).

Thy-1 triggers mouse thymocyte apoptosis through a bcl-2-resistant mechanism.

Programmed cell death plays an important role during thymocyte development, since a vast majority (97%) of mouse cortical thymocytes die in thymus, whereas only 3% of these cells are rescued from cell death and positively selected. Although it seems well established that thymocyte fate depends upon appropriate surface-expressed T cell receptor, little is known about the molecular mechanism(s) responsible for the massive thymocyte elimination that occurs in the thymus. We report here that Thy-1 is capable of triggering mouse thymocyte death in vitro through a bcl-2-resistant mechanism.

The impact of familial loading on gender differences in age at onset of schizophrenia.

To evaluate the impact of familial loading and gender on age at onset, 197 schizophrenic patients were investigated. Patients with familial loading had an earlier age at onset without gender differences. In contrast, an earlier age at onset for men was found in sporadic cases.

Thy-1 functions as a recognition/signaling molecule during mouse T lymphocyte development.

Thy-1 is a prototype of mammalian glycosyl phosphatidylinositol (GPI)-anchored molecules and belongs to the Ig superfamily. This cell surface glycoprotein is expressed on mouse T lymphocytes, neurons and hematopoietic stem cells. Despite detailed structural studies, little is known about the physiological role(s) of Thy-1.

Percutaneous absorption of estradiol and progesterone in normal and appendage-free skin of the hairless rat: lack of importance of nutritional blood flow.

Percutaneous absorption occurs after passive diffusion through the different layers of the skin and its appendages. Thereafter, a resorption process into the cutaneous microcirculation brings the compounds into the systemic circulation. The objective of this in vivo study in the hairless rat was to compare the percutaneous absorption of two steroids on normal and appendage-free (scar) skin and to show if differences in absorption result only from the lack of hair follicles and sebaceous glands and/or from a modification of local blood flow.

Role of transepidermal and transfollicular routes in percutaneous absorption of steroids: in vitro studies on human skin.

Percutaneous absorption theoretically comprises two components: the transepidermal and the transfollicular routes. The aim of the present work was to confirm this hypothesis in the human skin by comparing the in vitro percutaneous absorption of four steroids through scar skin without hair follicles and sebaceous glands and through normal adjacent skin from abdominal or mammary plasties. In all cases, the absorption of the four steroids was significantly higher in normal skin than in scar skin.

Sulfated glycans directly interact with mouse Thy-1 and negatively regulate Thy-1-mediated adhesion of thymocytes to thymic epithelial cells.

Thy-1 is a major brain cell surface glycoprotein of adult mammal species also expressed in rodent thymus. Despite extensive studies, the function(s) of this molecule has remained so far ill defined. We have recently shown that Thy-1 was involved in the adhesion of mouse thymocytes to thymic epithelium through a specific interaction with a heterophilic ligand(s) expressed on the epithelial cell surface.

Role of transepidermal and transfollicular routes in percutaneous absorption of hydrocortisone and testosterone: in vivo study in the hairless rat.

The importance of the transappendageal route on percutaneous absorption was assessed in the hairless rat. Skin permeation of two steroids, hydrocortisone and testosterone, was evaluated in vivo on normal and artificially damaged skin in which follicles and sebaceous glands disappeared during healing. The test compounds were applied for periods of 0.

X-linked recessive nephrolithiasis with renal failure.

Background And Methods: Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members.

Improved subtraction technique in intravenous digital left ventriculography: comparison with radionuclide studies.

Adequate processing of left ventricular angiograms depends on the visualisation of all segments of the ventricular wall. At the same time, subtraction of different images can enhance different heart segments but commercially available methods do not allow simultaneous viewing of several images masked by different processes. Using our software, for each studied frame, a four quadrant display permits the simultaneous visualisation of a mask mode image, a diastolic-systolic difference image, an image obtained by subtraction of a frame at the same cycle time and a composite mask subtracted image.

[Value of digital subtraction of left ventriculographies by the venous route. Comparison with balanced scintigraphy of the heart cavities].

The development of numerisation material in radiology currently permits to perform usual cardiovascular tests. The authors report a series of 48 patients who benefited from the determination by numerised left ventriculography, of their stroke volume (SV). In 37 cases, the peripheral venous route is used while in 11 cases the central venous route is used, in the pulmonary artery trunk.

[Hemolytic anemia and cardiac heterografts. Apropos of 2 cases].

Two cases of severe haemolytic anaemia developed after heterograft valve replacement are reported. In one case haemolysis was caused by prosthetic degeneration; in the other case the heterograft was not altered, but a ventricular septal defect had created a high turbulence around the valve which was in pulmonary position. In both cases anaemia subsided after surgical correction of the abnormalities responsible for periprosthetic turbulence.

Suppression of vascular prostacyclin generation by jaundiced serum: relation to lipid peroxides.

Jaundiced serum has been shown to increase vascular sensitivity to the pressor effect of catecholamines. To determine whether this effect is caused by decreased vascular production of the vasodilator prostacyclin, we compared the ability of normal and jaundiced human serum to promote prostacyclin production in rat aortic tissue. Vascular prostacyclin production was significantly decreased after incubation of aortic tissue with jaundiced serum as compared with normal serum.

Effects of histidine on vasopressin action: role of decreased prostaglandin production.

Addition of histidine to the serosal bath of the toad bladder increases the hydrosmotic response of vasopressin in this tissue. Because this represents primarily the effect of the imidazole ring of histidine, which is a known inhibitor of the production of prostaglandins, we evaluated whether histidine increases the response to vasopressin through decreased prostaglandin production. Histidine increases the response to vasopressin much more than 10(-5) M naproxen, even though the latter was equipotent to histidine in reducing prostaglandin E2 (PGE2) production.

[Testicular echography in torsion and epididymitis. Apropos of 2 cases].

We report two cases, one of a long-standing epididymitis with a testicular infarct, the second of testicular tumor with torsion. Scrotal ultra-sound is a quick, easily applied, accurate method to follow cases of subacute epididymitis with atypical evolution. In case of testicular torsion, secondary to tumor, it helps to rule out scrotal exploration and to decide of an orchidectomy with a high located surgical approach.