Autoimmunity after allogeneic bone marrow transplantation. A study of 53 long-term-surviving patients.

Various autoantibodies were screened in 53 long-term survivors after allogeneic bone marrow transplantation. Among them, 40 displayed chronic graft-versus-host disease, with clinical features reminiscent of collagen diseases, especially scleroderma, Sjögren's syndrome, and autoimmune hepatitis. Antinuclear, anti-smooth muscle, antimitochondria, anti-liver kidney microsome, and antiepidermal antibodies were found at a frequency of 62.2%, 49.0%, 11.3%, 5.6%, and 11.3%, respectively. The screening for native anti-DNA, anti-extractable nuclear antigen, anticentromere, and anti-salivary gland duct antibodies was negative. The presence or absence of acute GVHD made no difference in the frequency of autoantibodies. No correlation between cutaneous hepatic involvement, sicca syndrome, scleroderma status, and autoantibodies could be established. Despite clinical features mimicking collagen vascular diseases, the biological autoimmune profile of GVHD was different. The precise role of autoimmunity in chronic GVHD remains to be defined.

Differential transferrin receptor density in human colorectal cancer: A potential probe for diagnosis and therapy.

Transferrin receptor density was investigated in human colorectal surgical specimens. Crude membranes were prepared from 23 cancer tumors (adenocarcinoma or malignant villous tumor) and 3 non-cancer tumors (polyadenoma or villous tumor) and 26 adjacent control mucosa. Contrary to non-cancer tumors, Scatchard analysis of 125I-transferrin binding data evidenced higher maximal transferrin binding capacity and lower dissociation constant in cancer tissues (Bmax cancer 1.828+/-0.320 nmol/g, Kd 24.1+/-4.7 nM), as compared to paired control colonic mucosa (Bmax contol 0.851+/-0.182 nmol/g, Kd 30.7+/-7.3 nM), paired t-tests: Bmax p<0.001, Kd p<0.05). As the cancer/control Bmax ratio was 2.6+/-0.4,transferrin carrier constructs should be proposed for cancer imaging or therapy.

Low molecular weight hydroxyethyl starch 6% compared to albumin 4% during intentional hemodilution.

Intentional normovolemic hemodilution was chosen as the model to compare a 6% low molecular weight hydroxyethyl starch (LMW HES) to 4% albumin. The study ran over the plasma exchange period for 24 h. Nine patients, scheduled for abdominal aortic surgery, were included in each group. After basal measurements, blood was withdrawn and simultaneously replaced by either 4% albumin (Group 1) or 6% LMW HES (Group 2) to achieve a final hematocrit of approximately 30%. Hemodynamic blood oxygen gas and hormonal plasma levels were determined before hemodilution then at 30 min, 1, 2, 3, and 24 h after the end of hemodilution. Basal value for total blood volume was 4377 +/- 162 ml in group 1 and 4138 +/- 315 ml in group 2. As in both groups the decrease in blood cell volume was exactly compensated by the increase in plasma volume, no significant change in total blood volume (respectively 4432 +/- 159 and 4305 +/- 267 ml) was observed. Throughout the study, in both groups, no significant change in mean arterial and right atrial pressures was observed. In group 2 (LMW HES), a significant increase of pulmonary capillary wedge pressure was noted 120 min after hemodilution. After hemodilution, despite a significant decrease in arterial oxygen O2 content, systemic oxygen transport did not significantly vary until 24 h in relation to the increased cardiac index. An increase in O2 extraction was observed after the exchange but no further increase was observed until the 24 h. No significant changes either in global O2 consumption or in lactate concentration were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide during water deprivation or hemorrhage in rats. Relationship with arginine vasopressin and osmolarity.

The concentrations of atrial natriuretic peptide (ANP) in atria, hypothalami and plasma were investigated in relation to the variations of the plasma endogenous immunoreactive arginine vasopressin (Ir-AVP) during water deprivation or hemorrhage in normal conscious Wistar rats. Furthermore, the in vitro and in vivo effect of extracellular hyperosmolarity on ANP release from right atrium and hypothalamus was examined. Water deprivation elevated circulating immunoreactive ANP (Ir-ANP: pg/ml) to 153 +/- 7 (24 h); 174 +/- 1 (48 h) from the control level (109.6 +/- 7.8). This increase in Ir-ANP concentration which correlated with atrial (r = -0.93) or hypothalamic (r = -0.87) Ir-ANP content decrease, was associated with significantly enhanced levels of plasma Ir-AVP, plasma sodium, osmolarity and hematocrit. An acute volume depletion by hemorrhage significantly reduced plasma Ir-ANP (67 +/- 8.4 pg/ml) from the sham operated level (140 +/- 18 pg/ml). Plasma Ir-AVP was elevated dramatically (207.4 +/- 53.4 pg/ml) compared with the sham operated level (8.8 +/- 2.6 pg/ml). These results, indicating the lack of correlation between plasma Ir-ANP and Ir-AVP in vivo, suggest that the ANP secretion, which is regulated mainly by plasma volume, may be modulated by a change in plasma osmolarity. Extracellular hyperosmolarity stimulated the ANP release from superfused sliced normal rat atria and hypothalami.

Comparing HEp-2 cell line with rat liver in routine screening test for antinuclear and antinucleolar autoantibodies in autoimmune diseases.

The comparative study of the human tumor cell line HEp-2 and rat liver for the detection of antinuclear and antinucleolar autoantibodies by the indirect immunofluorescence technic in routine screening test demonstrate that, taking titer and staining pattern into account, both substrates are able to separate autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, scleroderma and primary biliary cirrhosis) patients from healthy subjects. The minimal screening test must include sera diluted 1:20 and 1:80. The capability of the HEp-2 substrate to reveal and to discriminate different speckled nuclear and nucleolar patterns explain its greater performance, notably in detecting anticentromere antibodies highly specific for the CREST syndrome and a speckled nuclear antibody frequently associated with primary biliary cirrhosis, allowing an earlier diagnosis of autoimmune diseases presenting these patterns.

[Comparison of human tumor cells (Hep 2) and rat liver for the detection of antinuclear antibodies by indirect immunofluorescence]. / Comparaison cellules tumorales humaines (Hep 2) et foie de rat pour la détection des anticorps antinucléaires en immunofluorescence indirecte.

Indirect immunofluorescent detection of anti-nuclear antibodies was conducted on sections of rat liver and on smears of human Hep 2 tumour cells in the serum of 1017 patients. Overall, the Hep 2 cells gave titres superior by 1 or 2 dilutions. Taking into account this difference, a good agreement was observed between the 2 cellular reagents in 83 per cent of the sera tested. The divergences, which affect almost one half of the positive sera, are largely due to the presence of anti-centromere antibodies, anti-nuclear antibodies giving a patchy "M3" appearance to the Hep 2 cells and, most importantly, anti-nucleolar antibodies. Such differences demonstrate that there are major qualitative or quantitative antigenic differences between the nuclei of rat hepatocytes and those of Hep 2 cells. Although technically rat liver and Hep 2 cells were found to be fairly easy to use and interpret, only a large comparative study of human pathology will be able to determine which is the better reagent for the routine detection of anti-nuclear antibodies.

[Anti-centromere antibody, biological marker of the CREST syndrome as distinct from scleroderma]. / L'anticorps anticentromère, marqueur biologique de la variété CREST de la sclérodermie.

Using HEp2 cells to study antinuclear antibodies has resulted in the discovery of the anti-centromere antibody which is thought to separate the CREST syndrome from progressive systemic sclerosis (scleroderma). This antibody seems to be exceptional in healthy subjects and are in patients with connective tissue diseases, except for scleroderma. It has also been found in CREST syndrome associated with other diseases, such as primary cirrhosis and neoplasias. In our study, the sensitivity of the anti-centromere antibody was 89.1% and its specificity 92.3% which shows that it is worth looking for.

Tissue distribution of 131I radiolabeled transferrin in the athymic nude mouse: localization of a human colon adenocarcinoma HT-29 xenograft.

The tissue distribution of 131I-transferrin (131I-Tf) was studied in athymic nude mice having s.c. human colonic adenocarcinoma HT-29 xenografts. Four days after 131I-Tf injection, the 131I-specific activity measured in the HT-29 tumor, i.e. amount of radioactivity per gram of fresh tissue, represented 0.31 +/- 0.09% of the injected radioactivity and was 1.90 fold more than that measured in the murine colon (P less than 0.05). After correction for intravascular 131I-Tf as estimated by means of 99mTc-Sn in vivo labeling of red blood cells, the 131I specific activity observed in the HT-29 tumor was 7.21 fold more than that observed in the murine colon. This subtracting method enabled us to localize a HT-29 tumor xenograft by gamma scintigraphy of the entire animal and demonstrated that 131I-Tf could be a non-specific but potent marker for human colon cancer.