In vivo R1-enhancement mapping of canine myocardium using ceMRI with Gd(ABE-DTTA) in an acute ischemia-reperfusion model.

PURPOSE: To demonstrate the usefulness of normalized DeltaR1 (DeltaR1(n)) mapping in myocardial tissue following the administration of the contrast agent (CA) Gd(ABE-DTTA). MATERIALS AND METHODS: Ischemia-reperfusion experiments were carried out in 11 dogs. The method exploited the relatively long tissue lifetime of Gd(ABE-DTTA), and thus no fast R1 measurement technique was needed. Myocardial perfusion was determined with colored microspheres (MP). RESULTS: With varying extent of ischemia, impaired wall motion (WM) and lower DeltaR1(n) values were detected in the ischemic sectors, as opposed to the nonischemic sectors where normal WM and higher DeltaR1(n) were observed. Based on the DeltaR1(n), data from the myocardial perfusion assay and the DeltaR1(n) maps were compared in the ischemic sectors. A correlation analysis of these two parameters demonstrated a significant correlation (R = 0.694, P < 0.005), validating the DeltaR1(n)-mapping method for the quantitation of ischemia. Similarly, pairwise correlations were found for the MP, DeltaR1(n), and wall thickening (WT) values in the same areas. Based on the correlation between DeltaR1(n) and MP, DeltaR1(n) maps calculated with a pixel-by-pixel resolution can be converted to similarly high-resolution myocardial perfusion maps. CONCLUSION: These results suggest that the extent of the severity of ischemia can be quantitatively represented by DeltaR1(n) maps obtained in the presence of our CA.

99m Tc-HMPAO labelled leukocyte scintigraphy in patients with rheumatoid arthritis: a comparison with disease activity.

The aim of this study was to test the applicability of 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leukocyte joint scintigraphy in the assessment of disease activity in 21 patients with rheumatoid arthritis, and to compare leukocyte scintigraphy with the Disease Activity Score (DAS), a validated activity index developed by the European League Against Rheumatism (EULAR). Twenty-one patients with rheumatoid arthritis were investigated by using 99mTc-HMPAO labelled leukocyte joint scintigraphy. The clinical and laboratory data were recorded, and the DAS was calculated and compared with the scintigraphic results in each case. A relatively high DAS score (4.71+/-1.07) was found in the majority of patients. The degree of accumulation of 99mTc-HMPAO leukocytes showed no correlation with a patient's age, gender, duration of disease, use of disease modifying anti-rheumatic drugs (DMARDs), visual analogue scale (VAS), Richie index, DAS, or any laboratory parameters. In contrast, a significant correlation was found between the global regional accumulation of the labelled leukocytes of the hands and feet, and the swollen-joint count. It is concluded that radiolabelled leukocyte scintigraphy could become one of the promising methods in the assessment of disease activity in patients with rheumatoid arthritis.

Flow cytometric assay of phagocytic activity of human neutrophils and monocytes in whole blood by neutral red uptake.

In a new, simple, and fast flow-cytometric method for the simultaneous measurement of phagocytic activity of human neutrophils and monocytes in whole blood, the fluorescence capability of the well-known vital stain, neutral red was used. The incubation of 0.5 ml heparinized human blood with the phagocytic stimulus of zymosan dose- and time-dependently increased the percentage and the red fluorescence intensity of both neutrophils (4.3 +/- 1.2 times) and monocytes (2.7 +/- 0.7 times) measured cytofluorimetrically. Decreased uptake of neutral red was observed in a patient with phagocytic disorder, based upon impaired engulfment of particles and production of reactive oxygen species. In a patient with chronic granulomatosis, however, no decrease of neutral red uptake was measured. Platelet activating factor and phorbol myristate acetate were also able to increase the uptake of neutral red by both monocytes and neutrophils, but to a lesser extent than zymosan. The advantage of this method is the possibility for the simultaneous measurement of phagocytic activities of monocytes and neutrophils stimulated by either particles or soluble activators. This method is suitable for the selective measurement of activation processes not related to the production of free radicals in the phagocytes.

Correlations of monocyte phagocytic receptor expressions with serum immune complex level in systemic lupus erythematosus.

The expression of Fc gamma RI, Fc gamma RII, and Fc gamma RIII (the IgG receptors CD64, CD32, CD16) as well as CR3 (the C3bi receptor, CD11b) on monocytes in the blood of patients with systemic lupus erythematosus (SLE) was investigated. The relationship between the receptor expression and the serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity (FI) of the Fc gamma RII of patients' monocytes stained by specific monoclonal antibodies (MoAb IV3) was very close to statistical significance (P = 0.052). The expression (FI) of CR3 (using MoAb OKM1) on monocytes of patients was also decreased, but not significantly. The detected decrease of Fc gamma RII and CR3 was inversely correlated with the high circulating immune complex level in patients' sera. At the same time, Fc gamma RI expression on SLE monocytes (using MoAb 32) was significantly elevated and this change was in parallel with the serum IC concentration.

HTLV-related markers in a Hungarian patient with adult T-cell leukemia.

Monoclonal integration of DNA sequences related to, but not identical to HTLV-I provirus was detected in the peripheral blood lymphocytes of a Hungarian male suffering from ATL. The patient and his parents showed serological cross-reactivity with both HTLV-I and HTLV-II group-specific antigens. Restriction enzyme analysis with EcoRI, PstI, BamHI, HindIII and SacI revealed structural similarity of the provirus integrated in the DNA of ATL cells to HTLV-I but not to HTLV-II. Data suggest that this provirus and HTLV-I are similar to each other along gag and pol regions, but they are different in the env region.

Demonstration of HTLV-related proviral DNA sequences and antibodies reactive with HTLV internal proteins in an Hungarian patient with Sézary syndrome.

DNA sequences distantly related to the proviral DNA of HTLV-I were found in the leukemic cells of a Hungarian patient suffering from Sézary syndrome. Serum samples from the patient contained antibodies reactive with the internal core polypeptides of HTLV-I and HTLV-II, but not with the env gene encoded type-specific HTLV antigens. The husband and daughter of the patient also had antibodies of the same specificity. These findings suggest the presence of a virus distantly related to HTLV-I and HTLV-II.

Marker profile, enzyme activity, and function of a human myelomonocytic leukemia cell line.

Morphological and functional characteristics of a permanent human leukemia cell line (DD) that possesses myelomonocytic features were investigated. The cells bear a second type Fc gamma receptor and form rosettes with sheep erythrocytes sensitized with rabbit IgG (EA). However, the surface-bound EA is not internalized. The cell line lacks the surface markers CD2, CD19, CD14, HLA-DR, Fc gamma receptor I, Fc gamma receptor III, and CR3. alpha 1-Antitrypsin, lysozyme, Factor XIII a subunit of blood coagulation, and acid phosphatase reactions were negative. A terminal differentiation of the DD cell line was observed when the expression of CD14, CR3, Fc gamma receptor I, and Fc gamma receptor III was induced. The DD cells induced with 12-O-tetradecanoylphorbol-13-acetate or Escherichia coli lipopolysaccharide can internalize EA via Fc gamma receptor II and complement-coated yeast in the function of the inducers. The phagocytic ability appears to be parallel with the appearance of enzymes which participate in phagocytosis.

Phagocytosis of autologous platelets by human neutrophil granulocytes.

The phenomenon that the autologous human platelets can be phagocytosed in vitro by neutrophils and monocytes of healthy human donors (being free of antiplatelet autoantibodies) was demonstrated earlier. In this study we have confirmed electron microscopically the phenomenon of phagocytosis. Besides, using flow cytometric analysis, we have shown that a possible way for the bridge-formation between the washed platelets and neutrophils can be the linkage via IgG + C3b complexes bound to the Fc receptors of platelets. This mechanism supposedly may play a role also in the clearance of platelets by peripheral phagocytes in vivo.

[Reflections on non-differentiated collagenosis or non-differentiated autoimmune syndrome]. / Gondolatok a Nem Differenciált Collagenosisról (NDC), illetve a Nem Differenciált Autoimmun Syndromáról (NAS).

The authors review the Non-Differentiated Collagenosis (NDC) described by Gyula Petrányi 29 years ago, and try to establish whether it is still necessary to maintain this clinical picture. Relying on data from special literature and on their own findings, the authors conclude that the maintenance of the NDC terminology is justified by the fact that poly-systemic autoimmune diseases take time to develop and that at certain stages of this development it is almost impossible to make a firm decision as to which clinical picture the process will lead to. The authors discuss the clinical and immunological features of NDC, the implications for the patients and things to be done in order to recognise the NDC disease process. They also emphasize a more frequent occurrence of the features of NDC than is generally stated, and that such patients need regular, competent and devoted medical attention.

CD5 positivity on peripheral blood B lymphocytes in patients with primary Sjögren's syndrome.

The increased number of the CD5+ (Leu 1) B cells in 9 of 17 patients with primary Sjögren's syndrome (SS) were found in this study. The percentage of CD5+ B cells that demonstrated an increased number of these cells was more than 45% in patients with pSS, and the normal level 26.3 +/- 8.8% in control subjects. The ratio of the CD5+ B cells was higher if the pSS was in the active stage.

B lymphocyte subsets in Hashimoto's thyroiditis.

Two B lymphocyte subsets are identified on the basis of possession or lack of a surface molecule, CD5. The CD5+ B lymphocytes synthesize autoantibodies and in the process rearrange proximal variables of immunoglobulin genes. We have here studied the proportion and absolute counts of CD5+ B lymphocytes in the peripheral blood of 31 patients with Hashimoto's thyroiditis and related the findings to their HLA phenotypes and clinical features. Although the percentage and absolute number of surface immunoglobulin-positive (B) lymphocytes was comparable in patients to those in twenty controls, % CD5+ was significantly higher in the patient group (38.1 +/- 11.6 [+/- S.D.] vs. 27.9 +/- 10.1, p = 0.009). The absolute CD5+ cells (microliters) were also higher in patients with Hashimoto's thyroiditis (77.90 +/- 37.50 vs. 55.1 +/- 29.8, p = 0.020). The proportion of CD5+ cells was even higher in HLA-DR3 positive patients (43.1% +/- 7.2, n = 13) compared to six DR3+ controls (26.17% +/- 9.7, p = 0.0005). The difference between DR3- patients and controls was not significant (28.6% +/- 10.5 vs. 34.4% +/- 13.0). As the CD5 molecule may be induced on activated B lymphocytes, this study suggests that Hashimoto's thyroiditis is associated with an increase of activated B lymphocytes engaged in autoantibody synthesis. This defect is particularly obvious in DR3+ patients.

Immunogenetic and immunologic studies of differentiated thyroid cancer.

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell-mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/normal tissue interface. HLA-DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DR1 homozygotes were not at greater risk for thyroid cancer. The HLA-DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA-DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (less than 45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell-mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA-DR could not be related to cell-mediated immune response. Patients with papillary carcinoma with a good cell-mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell-mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.

Methimazole blocks Graves' IgG but not interferon-gamma HLA-DR expression by thyroid cells.

We have expanded our early observation that a potent Graves' IgG preparation induces HLA-DR expression on thyroid cells, by showing that four randomly-selected Graves' IgG's were also capable of inducing DR antigens on thyroid cells. The effect of Graves' IgG was specific to thyroid cells, as it did not induce MHC Class II molecule expression on endothelial cells whereas interferon-gamma and immune complexes did so. The anti-thyroid drug methimazole was capable of rapidly reducing Graves' IgG-induced DR expression but to a much lesser extent than brought about by interferon-gamma. We conclude that Graves' IgG propagates thyroid-specific autoaggression by continued induction of DR antigens and than an important means whereby methimazole brings about remission is by reducing this induction.