TN Patients Research Articles

Fluid state and blood pressure control in patients treated with long and short haemodialysis.

Patients treated at the haemodialysis (HD) centre in Tassin, France have been reported to have superior survival and blood pressure (BP) control. This control has been ascribed to maintenance of an adequate fluid state, antihypertensive drugs being required in < 5% of the patients, although it could not be excluded that a high dose of HD regarding removal of uraemic toxins might also have been of value. The aim of the study was to assess the fluid state and BP in normotensive patients on long HD (8 h) in Tassin (group TN) using bioimpedance to measure extracellular volume (ECV), ultrasound for determining the inferior vena cava diameter (IVCD), and 'on-line' monitoring of the change in blood volume (BV), and to compare them with normotensive (group SN) and hypertensive (group SH) patients on short HD (3-5 h) at centres in Sweden. ECV was normalized (ECVn) by arbitrarily setting the median ECV (in % of body weight) in SN patients at 100% for each gender, recalculating the individual values and combining the results for male and female patients in each group. The dose of HD (Kt/V urea) was higher for TN patients than for Swedish patients who had a similar Kt/V, whether hypertensive or not. SH patients had significantly higher ECVn and IVCD than TN and SN patients. TN and SN patients did not differ significantly regarding ECVn and IVCD before and after HD. However, in a subgroup of eight TN patients, ECVn was below the range of that in SH and SN patients, due to obesity with a high body mass index. Another subgroup of 14 TN patients had a higher ECVn than most of the SN patients and also higher than the median ECVn in the SH group, without any difference in body mass index, but they were nevertheless normotensive. The fall in BV was greater in SN than in TN patients, presumably due to a higher ultrafiltration rate in SN patients. However, SH patients had a smaller change in BV than SN patients, presumably because their state of overhydration facilitated refilling of BV from the interstitial fluid. Normotension can be achieved independently of the duration and dose (Kt/V urea) of HD, if the control of post-dialysis ECV is adequate. However, this is more difficult to achieve with short than with more prolonged HD during which the ultrafiltration rate is lower, BV changes are smaller and intradialysis symptoms less frequent. The results in the subgroup of patients with high ECVn at Tassin suggest that normotension may also be achieved in patients with fluid overload provided that the dialysis time is long enough to ensure more efficient removal of one or more vasoactive factors that cause or contribute to hypertension.

Repressed β-1,3-galactosyltransferase in the Tn syndrome

The human hematopoietic disorder named Tn syndrome has been ascribed to an acquired stem cell mutation resulting in loss of β-1,3-galactosyltransferase activity in affected Tn+ cells of the hematopoietic lineages. Recently, we could demonstrate that this deficiency is due to a repression of a functional allele of the β-1,3-Gal-T gene since treatment of Tn+ T-lymphocytes from a patient (R.R.) afflicted with the Tn-syndrome with 5-azacytidine or Na n-butyrate resulted in re-expression of the Thomsen–Friedenreich (TF) antigen, the product of β-1,3-Gal-T activity [M. Thurnher, S. Rusconi, E.G. Berger, Persistent repression of functional allele can be responsible for galactosyltransferase deficiency in Tn syndrome, J. Clin. Invest. 91 (1993) 2103–2110]. To reduce these observations to a common pathogenetic mechanism responsible for the Tn-syndrome, more Tn patients need to be investigated. Here, we describe similar Tn+ T-lymphocytes cultured ex vivo from patient M.Z. whose Tn+ syndrome was newly recognized. Tn+ and TF+ T-lymphocyte cultures were characterized by flow cytometry and measurement of β-1,3-Gal-T and shown to be deficient in Tn+ cells. Furthermore, Tn+ cells were treated with 5-azacytidine and Na n-butyrate as described before. Reoccurrence of β-1,3-Gal-T activity dependent epitopes on the cell surface of Tn+ cells was shown by flow cytometry. These support the notion of β-1,3-Gal-T gene repression as a common pathogenetic mechanism underlying the Tn-syndrome.

Presence of the Tn antigen on hematopoietic progenitors from patients with the Tn syndrome.

The Tn syndrome is an acquired clonal disorder characterized by the exposure of a normally hidden determinant, the Tn antigen, on the surface of human erythrocytes, platelets, granulocytes, and lymphocytes. Two distinct populations, Tn positive (Tn+) and Tn negative (Tn-), of mature hemopoietic cells are present in Tn patients. To determine whether the Tn antigen is already expressed on erythroid, myeloid, and pluripotent progenitors, light-density mononuclear blood cells from two patients with this syndrome were separated by fluorescent-activated cell sorting and by affinity chromatography into Tn+ and Tn- fractions, using their binding properties to Helix pomatia agglutinin (HPA). Burst-forming-unit erythroid (BFU-E), colony-forming-unit granulocyte/macrophage (CFU-GM), cells were assayed in plasma clot cultures. After 12-14 d of culture, colonies were studied by a double fluorescent labeling procedure. First, a fluorescein-conjugated HPA permitted evaluation of the presence or absence of the Tn antigen at the surface of the cells composing each colony, and second, the binding of a murine monoclonal antibody against either glycophorin A (LICR-LON-R10) or against a myeloid antigen (80H5), revealed by an indirect fluorescent procedure, was used to establish the erythroid or myeloid origin of each cell. The Tn+ fraction obtained by cell sorting gave rise to nearly 100% Tn+ colonies composed exclusively of cells bearing this antigen. The reverse was observed for the Tn- cell fraction. These results demonstrate that in the Tn syndrome, BFU-E, CFU-GM, and CFU-GEMM of the Tn+ clone express the Tn antigen at this early stage of differentiation.

Demonstration of T-transferase deficiency in Tn-polyagglutinable blood samples.

The serum and red cell membranes from seven Tn individuals have been tentatively characterized for the UDPgalactose: N‐acetyl‐d‐galactosamine‐β‐d‐galactosyltransferase and UDPgalactose: N‐acetyl‐d‐glucosamine‐β‐4‐d‐galactosyltransferase activities using p‐Nitrophenyl‐2‐acetamido‐2‐deoxy‐α‐d‐galactopyranoside and p‐Nitrophenyl‐2‐acetamido‐2‐deoxy‐β‐d‐glucopyranoside respectively as low molecular weight acceptors. In five cases, Tn‐positive and Tn‐negative red cells were at first separated by Polybrene differential aggregation. The following conclusions have been drawn. The β‐3‐d and β‐4‐d‐galactosyltransferases activities are found in serum and red cell membranes from all normal individuals. Polybrene‐positive cells (normal sialic acid content) from Tn bloods have either normal or higher β‐3‐d and β‐4‐d‐galactosyltransferases activities. Polybrene‐negative cells (low sialic acid content) from Tn bloods have a selective deficiency in β‐3‐d‐galactosyltransferase (T‐transferase) activity, but normal or even increased β‐4‐d‐galactosyl‐transferase activity. The serum from all Tn individuals behaves like normal sera in respect of the two galactosyl‐transferase activities. The serum may also be used as source of enzyme for conversion in vitro of Tn to T‐reactive erythrocytes. The above data strongly support the view that Tn‐polyagglutination results from a somatic mutation in stem cells of haematopoietic tissue which involves a single genetic step in red cell glycoprotein synthesis. It also provides further evidence of a dual population of erythrocytes in each Tn blood sample and suggests that T‐transferase found in serum is produced in unidentified cells of the organism. No difference has been noticed between apparently healthy Tn donors and Tn patients.