Highly active anti-retroviral therapy (HAART) is associated with a lower level of CD4+ T cell apoptosis in HIV-infected patients.

HAART may increase CD4+ T cell counts despite a persistently detectable HIV load. The impact of HAART on apoptosis, which may play a role in the disease process in HIV-infected patients, has not been extensively studied. We performed a study to compare the level of spontaneous T cell apoptosis and anti-retroviral treatments in a cohort of HIV-1-infected patients. Data were obtained from a computerized medical record. Quantification of apoptotic cells was by cytofluorometric technique. From November 1995 to December 1997 we studied T cell apoptosis in 112 HIV-infected patients. Forty patients were classified A, 36 B and 36 C. Thirty patients were naive and 82 received an anti-retroviral treatment, 49 including a protease inhibitor (PI). The median plasma viraemia determined in 63 patients was 3.6 (range 1.3-5.6) log10. The median apoptotic cell count was 22% (range 2-73%) and 12% (range 2-60%) for CD4+ and CD8+ T cells, respectively. We did not observe any correlation between the HIV viraemia and the level of apoptosis of T cell subsets. Patients with HAART showed a lower percentage of apoptotic CD4+ T cells only: 16% (range 2-61%) versus 25% (range 5-73%) for patients receiving two nucleoside analogues (P = 0.02). This effect was significant in stage A patients and remained observable during the whole course of HIV disease. In conclusion, HAART, without any relation to plasma viraemia, is able to reduce apoptosis of CD4+ T cells.

Overexpression of Fas/CD95 and Fas-induced apoptosis in a patient with idiopathic CD4+ T lymphocytopenia.

The mechanisms of apoptosis have become better understood, in part with the discovery of Fas/CD95. We report the case of a patient characterized by a decreased CD4+ T cell count and an overexpression of Fas/CD95 resulting in apoptosis. A 54-year-old man presented with disseminated Mycobacterium xenopi infection. Analysis showed CD4+ T lymphopenia. Tests for human immunodeficiency virus (HIV) types 1 and 2 were negative. We compared the patient with eight healthy controls and five HIV-infected patients in terms of the expression of Fas/CD95 and Fas-mediated apoptosis of peripheral T lymphocytes. The percent of CD95+ cells in lymphocytes was 98% for the patient, and the mean percent of CD95+ cells in lymphocytes +/- SD for HIV-infected patients and healthy controls was 75% +/- 16% and 36% +/- 26%, respectively. The patient had a high level of spontaneous apoptosis, and apoptotic cells were all identified as being CD4+ T cells. Monoclonal antibodies to CD95 dramatically increased apoptosis of CD4+ T cells exclusively. CD4+ T lymphopenia observed in our patient correlated with an overexpression of Fas together with spontaneous and Fas-induced apoptosis.

Thiol-mediated inhibition of FAS and CD2 apoptotic signaling in activated human peripheral T cells.

Fas and CD2 receptors can transduce apoptotic signals through two independent biochemical pathways. In this study, we first evaluated the role of intracellular GSH in these signaling pathways by inducing variations in the GSH pool of activated peripheral T lymphocytes. Increasing the concentration of intracellular GSH by means of N-acetyl-L-cysteine (NAC) and GSH ethyl ester (OEt) resulted in total protection against cell death, while inhibiting GSH synthesis with buthionine sulfoximine (BSO) greatly enhanced cell sensitivity to Fas and CD2 apoptotic signaling. The protection exerted by NAC and GSH OEt was essentially based on their capacity to establish an intracellular reducing environment as it still occurred in BSO-treated cells. Thiol-containing compounds (cysteine, captopril, D-penicillamine and 2-mercaptoethanol) inhibited apoptosis while a series of non-thiol antioxidants (including catalase and vitamin E) failed to do so, suggesting that protection was secondary to thiols/disulfides exchange reactions at the level of cysteine residues in proteins and not to detoxification of reactive oxygen intermediates. This conclusion was further supported by the finding that no enhanced generation of O.-2 and H2O2 could be detected in cells experiencing early stages of apoptosis such as a decreased concentration of intracellular GSH and cell shrinkage. Also, protection occurred in the presence of protein synthesis inhibitors, indicating that it was due to post-translational sulfhydryl redox regulation of critical molecules involved in the apoptotic cascade. These data suggest that GSH, the most abundant intracellular thiol antioxidant, may be important in counteracting Fas- and CD2-mediated apoptosis of T lymphocytes.

Reactive arthritis induced by Strongyloides stercoralis.

Reactive arthritis induced by Strongyloides is exceedingly rare. A case in a 53-year-old man from the Guadeloupe (French Antilles) is reported. The outcome was rapidly favorable under thiabendazole therapy. The cycle of Strongyloides is reviewed, and the contribution of parasites to reactive arthritis in patients with genetic risk factors is discussed. Establishing the correct diagnosis is sometimes difficult but is essential in order to avoid inappropriate administration of corticosteroids that can lead to fatal, multivisceral dissemination of the parasite, particularly in patients with strongyloidiasis.

CD59 molecule: a second ligand for CD2 in T cell adhesion.

The T cell surface molecule CD2 forms, with its counter-receptor CD58 (LFA-3), a powerful adhesion/activation pathway. There is some evidence that CD2 might bind more than a single ligand. Chinese hamster ovary cells (CHO) expressing human CD59 after cDNA transfection (CD59+CHO) form rosettes with human T cells; these rosettes are inhibited in a dose-dependent fashion by the CD59 monoclonal antibody (mAb) H19 and by the CD2 mAb O275 known to block natural rosettes, but not by the CD2R mAb D66, a poor rosette blocker. CD2+CHO transfectants form rosettes with human erythrocytes; these rosettes are inhibited by the CD59 mAb H19 in addition to CD2 mAb O275 and CD58 mAb; murine thymoma cells expressing human CD2 form rosettes with CD59+CHO cells that again are blocked by CD59 H19 and by CD2 O275 mAb. In a marked contrast with H19, two others CD59 mAb, YTH 53.1 and MEM 43, which react with a different epitope on CD59, led to a 50%-70% increase of the number of cells forming rosettes. In addition to rosette experiments, the binding of 125I-labeled CD59 molecules to CD2+CHO cells was specifically inhibited by unlabeled CD59 molecule and CD2 mAb. Furthermore, the binding of CD59 molecules to resting T cells induced expression of CD2R epitopes. These results directly show that CD2 binds CD59 and that subtle molecular changes occur upon binding.

Patent paraumbilical vein: anatomic and hemodynamic variants and their clinical importance.

Fifty-five of 353 patients with suspected portal hypertension studied with Doppler sonography had a patent paraumbilical vein. Of these 55 patients, 39 had the classic intrahepatic venous circulation found in Cruveilhier-Baumgarten syndrome: hepatopetal flow in all segmental portal veins and hepatofugal flow leaving the liver in a paraumbilical vein in the falciform ligament to join veins of the anterior abdominal wall. Sixteen patients had variants of the classic pattern: Flow in one or more segmental portal veins of the left lobe or the entire liver was hepatofugal. In addition, new venous channels connecting the left portal vein with the extrahepatic paraumbilical vein were found. Assessment of liver function with the Pugh score showed severe impairment in the majority of patients with a patent paraumbilical vein. Patients with the classic intrahepatic circulation had smaller esophageal varices than those with hemodynamic or anatomic variants. The presence of a patent paraumbilical vein did not prevent formation of esophageal varices in the patients studied.

Scintigraphic aspect of Rotor's disease with technetium-99m-mebrofenin.

A 28-yr-old male with Rotor's disease was studied with 99mTc-mebrofenin. The scintigraphic pattern was that of a slow liver uptake with unimpaired excretion and persistent visualization of the cardiac blood pool, kidneys and urinary tract up to 6 hr. The gallbladder was visualized at 55 min postinjection.

[Lymphocytic molecules implicated in rosette phenomenon. Differential effect of antilymphocyte serum on T (CD2+E2+) and B (CD2-E2+) lymphocytes]. / Molécules lymphocytaires impliquées dans le phénomène des rosettes. Effet différentiel du sérum anti-lymphocytaire sur les lymphocytes T (CD2+E2+) et B (CD2-E2+).

The molecule E2 is present on T lymphocytes and thymocytes and is implicated in rosette phenomenon most probably via interaction with CD2. The discrepancy observed between rosette levels and lymphocyte phenotypes in the follow-up of kidney-transplanted patients treated with antilymphocyte globulins (ALG), methylprednisolone and azathioprine leaded us to study the effect of ALG on E2 molecule.

[Autoantibodies in paraneoplastic polioencephalomyelitis: 8 cases]. / Auto-anticorps dans les polioencéphalomyélites paranéoplasiques: huit cas.

Antibodies directed against the central nervous system were looked for by indirect immunohistochemistry in the sera of 8 patients with paraneoplastic neurological syndrome (group 1), 21 cancer patients without neurological signs, 23 patients with miscellaneous neurological diseases and 63 normal subjects (groups 2 to 4). Four patients in group 1 had very high titres of antibodies. In 2 patients with small-cell lung carcinoma associated with sensory neuropathy the antibody recognized the cytoplasm and nucleus of all neurons. A 37 Kd protein was recognized by Western blot. A woman with cancer of the ovary and cerebellar syndrome exhibited an antibody against Purkinje's cell cytoplasm with a band of about 50-55 Kd at Western blot. In a woman with chronic uveitis and cerebellar atrophy with disappearance of Purkinje's cells the antibody (in blood and CSF) recognized certain layers of the retina as well as glial cells and cells present in the subependymal areas of the brain. Two bands of 46 and 59 Kd were revealed by Western blot. Immunoglobulins were detected in the cytoplasm of white matter cells in the cerebellum and brain stem. Among the other groups, one patient with lung cancer had a moderate titre of neuronal antinuclear antibody. The Western blot test was negative. The relevance of these antibodies for the diagnosis and treatment is discussed.

Renal transplantation with a current T negative but historical T and/or B positive cross-match.

We report our experience of 36 renal transplanted patients against a current T negative allo-cross-match, but historical T and/or B positive allo-cross-matches, whatever the result of the current B cross-match. Additionally, we have determined the immunoglobulin class of the antibody directed against B and T lymphocytes. The graft survival rate did not differ between the 36 patients forming the study group, and the 229 patients transplanted within the same period with negative T and B, on current and historical sera, cross-matches. Within this study group there was no changes in graft survival rate for the following three subgroups, which were retrospectively defined: historical positive (14 patients) versus negative (22 patients) T cross-match, current positive (15 patients) versus negative (21 patients) B cross-match, and IgM (16 patients) versus IgG (20 patients) against B lymphocytes. In terms of transplant outcome, our policy was thus safe.

Increased interleukin-2 receptor affinity in normal HLA A1 B8 DR3 subjects.

Twenty-two subjects (11 HLA A1 B8 DR3, 11 non-A1 B8 DR3) were tested for the capacity of their lymphocytes to express Tac molecules and interleukin-2 (IL-2) receptors (quantified using radiolabelled IL-2) after mitogen stimulation. Ten of these subjects (five A1 B8 DR3 and five non-A1 B8 DR3) were also tested for the ability of their lymphocytes to proliferate under IL-2 stimulation. A1 B8 DR3 subjects express a normal number of high-affinity IL-2 receptor sites, but the affinity of these receptors sites is significantly increased. Unexpectedly, A1 B8 DR3 lymphoblasts show a lower response to IL-2 than non-A1 B8 DR3 for high doses of recombinant IL-2.

[Immunogenetics of primary membranous glomerulonephritis]. / Immunogénétique des glomérulonéphrites extramembraneuses primitives.

In 65 patients with a biopsy-proven diagnosis of membranous glomerulonephritis, the association with HLA class I, class II and class III antigens was studied using classical techniques. We found a highly significant association with the HLA-DR3 (Pc = 8 x 10(-5)) antigen and with the HLA-B8 (Pc = 2 x 10(-4)) antigen in linkage disequilibrium with the former. In addition, there was an excess of null C4 allotypes (C4 AQo or C4 BQo) in patients and a significant decrease of BfS allele. Finally, the most commonly observed phenotype was A1 B8 DR3 BfS C4AQoB1. These results confirm a strong association between major histocompatibility complex and primary membranous glomerulonephritis, raising the possibility of a susceptibility gene being necessary for the development of that disease.

A complex t(3;8;17) involving breakpoint 8p11 in a case of M5 acute nonlymphocytic leukemia with erythrophagocytosis.

The t(8;16)(p11;p13) is a recently described new chromosome rearrangement of acute nonlymphocytic leukemia (ANLL). It appears to be specifically associated with acute monoblastic (AML-M5) or unusual myelomonocytic leukemia with prominent erythrophagocytosis in the leukemic cells. A complex t(3;8;17)(q27;p11;q12) is reported in a case of acute monoblastic leukemia with erythrophagocytosis. Sixteen cases of this t(8;16) and two other variant translocations are reviewed. The pathogenetic mechanism of the variant translocations is discussed, suggesting that the der(8) is a consistent recombinant.

Molecular diagnosis of chronic myeloid leukemia using a 3'bcr probe.

Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome which results from a reciprocal (9; 22) translocation, with the protooncogene c-abl moving from chromosome 9 to 22 and juxtaposed to the proximal bcr. Breakpoints on chromosome 22 are localized within 5.8 kb of the breakpoint cluster region (bcr). We have assessed the feasibility of using a 3'bcr probe for molecular diagnosis of CML. Thirty patients with Ph chromosome negative or positive CML were studied by Southern blot. A bcr rearrangement was seen to be present in all but one patient with Ph+CML. A case of Ph negative CML showed a bcr rearrangement. We conclude that this technique is efficient for molecular diagnosis of CML.

Hemodynamic changes in portal circulation after portosystemic shunts: use of duplex sonography in 43 patients.

Forty-five patients with 46 surgical portosystemic shunts were examined by duplex Doppler sonography, and the results were compared with those of esophageal endoscopy, angiography, surgery, and clinical follow-up. Thirty-eight shunts were patent, and in 33 of these, the shunt was directly visualized and flow was observed with Doppler sonography. Eight shunts were obstructed. After a successful portosystemic shunt procedure, flow in the shunted splanchnic vein was directed toward the shunt and the systemic vein. We studied the intrahepatic portal venous circulation in all of the patients; we found that in the presence of patent portosystemic shunt, portal flow is hepatofugal. This reversal of blood flow occurred in all but four patients. In the end-to-side portacaval shunt, where the portal vein is ligated, blood in intrahepatic portal branches presumably reaches the shunt through perihepatic collaterals. In the presence of a thrombosed shunt, intrahepatic portal venous flow was hepatopetal. To our knowledge, this is the first noninvasive in vivo study of intrahepatic portal circulation after portosystemic shunt surgery. The duplex Doppler evaluation of portosystemic shunts appears to be reliable and should be the method of choice for shunt patency assessment in patients with recurrent signs of portal hypertension. In addition to demonstrating flow at the site of the anastomosis, the Doppler study may yield an easy and reliable sign of shunt patency: reversed flow (hepatofugal flow) in the intrahepatic portal veins probably signals a patent shunt, even if the site of the anastomosis cannot be visualized directly by sonography.

Acceptance of a connective tissue equivalent for grafting and capsuloligamentary reconstruction.

A strip of a connective tissue equivalent prepared by using the patient's fibroblasts cultivated in vitro and calf skin collagen, was used for capsuloligamentary reconstruction of the knee. The study of the humoral and cell-mediated immune responses indicated that there was no cell-mediated immune reaction and only a transient humoral reaction 2 months after implantation. This first assay in human surgery gave a good functional result, and an immunological response was no longer observed 5 months after grafting.