Plasma levels of ICAM-1 and circulating endothelial cells are elevated in unstable types 1 and 2 diabetes.

OBJECTIVE: To investigate the expression and release of vascular cell-adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, endothelial leukocyte adhesion molecule (ELAM)-1 and von Willebrand factor (vWF), as well as circulating endothelial cells (CEC) and circulating endothelial progenitor cells (CEPC), as markers of endothelial dysfunction in uncontrolled, well controlled types 1 and 2 diabetic patients and non diabetic patients. METHODS: In this observational trans section study, soluble adhesion molecules concentrations were measured by enzyme linked immunosorbent assays and flow cytometry to detect circulating cells in 49 patients, stratified in 3 groups: G1: uncontrolled types 1 and 2 diabetic patients (n=16); G2: well controlled diabetic (types 1 and 2) patients (n=13); and G3: non diabetic patients (n=20), of whom a blood sample was obtained on admission. RESULTS: ICAM-1 increased significantly in uncontrolled versus well controlled and non diabetic patients (721 vs. 702.45 vs. 473.46 ng/ml, p=0.016). In unstable diabetic patients, CEC were higher than in the well controlled ones (7.75 vs. 4.3/ml, p=0.386) whereas CEPC were lower in unstable diabetics (56.5 vs. 72/ml, p=0.068). CONCLUSIONS: This study showed a continuous rise in ICAM-1 and CEC levels as stable, well controlled diabetic patients shift towards decompensation. In unstable diabetic patients, the relationship between CEC and CEPC can be represented as [CEC] alpha 1/[CEPC].

[Hydatid cyst of the parotid gland: six cases]. / Kyste hydatique parotidien: a propos de six cas.

Primary hydatid cyst of the parotid gland is still an exceptional localization. The parotid gland is an uncommon site, even in our country, in which echinococcal disease is endemic. We report six cases of primary hydatid cyst of the parotid gland who presented with an isolated mass. The diagnosis was based on ultrasonography, which showed a parotid gland cystic mass. The echinococcal immunologic test (enzyme-linked immunosorbent assay) was positive in two cases. The surgical treatment consisted of total resection of the cyst, without rupture of the cystic wall and preserving the gland, in four cases and resection of the prominent dome in two cases. The diagnosis was confirmed on macroscopic examination of the resected pieces. In all cases, the postoperative course was uneventful. There was no recurrence at the 17-month follow-up.

Gene therapeutic approaches to induction and maintenance of tolerance.

Tolerance induction would be an ideal way to treat autoimmune diseases, especially if achievable in primed individuals. Moreover, specific tolerance would preclude the need for immunosuppressive treatment with its side effects. In this review, we will revisit the historical concepts of tolerance, and introduce a novel approach to tolerance via gene therapy. Our model system is based on the tolerogenicity of IgG carriers and B-cell antigen presentation. Results with this model demonstrate that it is simple and effective even in primed recipients, and has proven efficacy in three autoimmune models. We discuss the mechanisms of tolerance with fusion IgG's and analyze how our model of gene therapy approached can be utilized to fit in the future treatment of autoimmune conditions.

Mechanisms of tolerance induction by a gene-transferred peptide-IgG fusion protein expressed in B lineage cells.

A gene therapy model has been designed to induce tolerance to multiple epitopes expressed in-frame on a soluble IgG fusion protein scaffold. Tolerance to the lambda repressor cI sequence p1-102 or its immunodominant epitopes (p12-26, p73-88) can be elicited when bone marrow (BM) or LPS blasts are transduced and injected into naive or even primed recipients. To explore the mechanism of tolerance, class II(-/-) (knockout, KO) BM cells were transduced with p1-102-IgG and transferred to irradiated recipients. These cells failed to induce tolerance to challenge with p1-102 epitopes, whereas transduced +/+ BM cells did. This supports the importance of class II MHC on the tolerogenic APC rather than secretion and representation in tolerogenesis. When BM cells from muMT KO mice were transfected with p12-26-IgG and injected into irradiated mice, these transduced BM cells also failed to induce tolerance to an immunodominant epitope. These results suggest the direct involvement of B cells in tolerance to p1-102 epitopes. IL-10 KO BM cells infected with a p12-26-IgG construct were still tolerogenic. Importantly, anti-CTLA-4 injections reversed tolerance in primed, but not in naive, recipients of transduced LPS blasts. These data emphasize the importance of MHC class II presentation, B cell involvement, and CTLA-4 engagement in induction and/or maintenance of tolerance.

Induction of hyporesponsiveness to intact foreign protein via retroviral-mediated gene expression: the IgG scaffold is important for induction and maintenance of immune hyporesponsiveness.

IgG molecules can be highly tolerogenic carriers for associated antigens. Previously, we reported that recipients of bone marrow or lipopolysaccharide-stimulated B-cell blasts, both of which were retrovirally gene-transferred with an immunodominant peptide in-frame with the variable region of a murine IgG heavy chain, were rendered profoundly unresponsive to that epitope. To further investigate whether tolerance to larger molecules can be achieved via this approach and whether the IgG scaffold is important for induction and maintenance of immunological tolerance, we engineered two retroviral constructs encoding the cI lambda repressor (MBAE-1-102 and MBAE-1-102-IgG) for gene transfer. Our results show that recipients of bone marrow or peripheral B cells, transduced with the MBAE-1-102-IgG recombinant, are hyporesponsive to p1-102. In addition, the self-IgG scaffold enhanced the induction and maintenance of such an immune hyporesponsiveness. Thus, our studies demonstrate that in vivo-expressed IgG heavy chain fusion protein can be processed and presented on the appropriate MHC class II, resulting in hyporesponsiveness to that antigen and offering an additional therapeutic approach to autoimmune diseases.

Guinea pig apolipoprotein D RNA diversity, and developmental and gestational modulation of mRNA levels.

We have isolated and characterized two molecular types of guinea pig (GP) apolipoprotein D (apoD) cDNA. The sequences of cDNA clones GP APO D-20 and -38 are 100 % homologous in their putative exons 2-5, as determined by analogy within human apoD gene, but they differ totally in their putative exon 1. RNase protection assays showed the presence of both apoD RNA types 20 and 38 in cauda epididymis. Northern blot analysis revealed four polyadenylated apoD bands at 3.2, 2.7, 1.7, and 1.0 kb. Types 20 and 38 specific probes hybridized with the major 1-kb mRNA and two of the three other minor RNA transcripts, respectively. Southern blot analysis revealed that the guinea pig genome probably contains one apoD gene. Our data also demonstrated that the cauda epididymis and fallopian tubes had an apoD mRNA concentration 100-fold higher than the liver, suggesting that the apoD gene expression could be associated with the presence of steroids. The levels of the 1-kb mRNA increased in the fallopian tubes and ovaries during gestation and were lower in fetal reproductive tissues and liver than in mature animals. No positive correlation was found between apoD and 3 beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3 beta-HSD) mRNA levels in these tissues, thus suggesting that high amounts of apoD mRNA are not necessarily associated with in situ progesterone synthesis. Taken together, our results indicate that both the guinea pig epididymis and fallopian tubes are excellent models to study the local role of apoD in steroid target tissues.

[Blunt injury of the larynx by hanging. X-ray computed tomographic aspect]. / Traumatisme fermé du larynx par pendaison. Aspect scanographique à propos d'un cas.

The closed laryngeal traumas by attempt of hanging are rarely studied by medical imaging. The lesions are evaluated by fiberoptic endoscopy and CT scan. We report a case of complicated lesions of the larynx with rupture of the cricothyroid membrane, diagnosed by CT scan and we discuss the usefulness of this technique.

[Acute leukemia in Dakar. Retrospective study apropos of 36 cases]. / Les leucémies aiguës à Dakar. Etude rétrospective à partir de 36 cas.

This study of acute leukaemia in adult at the two main hospitals in Dakar- the General Hospital from January 1980 to June 1986 and the A. Le Dantec Hospital from January 1978 to June 1986 - shows the progression of this ailment, which remains rare (0.85% of admissions - 5 cases per year). Certain clinical peculiarities are stressed (high frequency of infectious symptoms, considerable splenomegaly , adenopathy often present in acute myeloid leukaemia. More severe biological signs are evident than in series in the West, and (L.A.M.3) forms dominate. Grave developments are often the result of a shortage of diagnostic and therapeutic equipment. The authors stress the need to create a haematological clinic.