Blood plasma pseudouridine in patients with malignant proliferative diseases.

The blood plasma concentration of pseudouridine was estimated in 104 healthy adult subjects, and 108 patients suffering from malignant proliferative diseases. The HPLC method for simultaneous determination of pseudouridine and creatinine was applied. The average physiological concentration of pseudouridine in blood plasma was 2.43 +/- 0.97 mumol.l-1 or 29.15 +/- 7.40 mmol.mol-1 creatinine. The physiological urinary excretion of pseudouridine was 14.32 +/- 5.20 mumol.24 h-1.kg-0.75 or 19.60 +/- 5.22 mmol.mol-1 creatinine. Renal clearance of pseudouridine and endogenous creatinine were 4.04 +/- 0.99 and 5.50 +/- 1.46 ml.kg-0.75, respectively. A positive correlation (r = 0.55, P < 0.01) was found between age (in the range 20-92 years) and blood plasma pseudouridine concentration (mumol.l-1). By expressing plasma pseudouridine in relation to plasma creatinine, the apparent influence of non-metabolic factors (age, renal insufficiency, blood dilution) on the plasma pseudouridine concentration were largely excluded. Among haematological proliferative diseases the highest values of plasma pseudouridine concentrations were observed in chronic lymphocytic leukaemia (8.19 mumol.l-1; 54.9 mmol.mol-1 creatinine) and multiple myeloma (7.02 mumol.l-1; 52.5 mmol.mol-1 creatinine). In multiple myeloma, but not in chronic lymphocytic leukaemia, the plasma pseudouridine concentration depended on the clinical stage. A lower, but still significant response in non-Hodgkin's lymphoma was noted (4.03 mumol.l-1; 40.88 mmol.mol-1 creatinine). A significant increase of the plasma pseudouridine concentration was characteristic of adenocarcinomas of the large intestine, and it occurred in the early stages of malignant growth. In patients with lung cancer the plasma pseudouridine concentration was elevated only in advanced cases with metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of urinary neopterin and pseudouridine in patients with malignant proliferative diseases.

The HPLC method for the simultaneous determination of urinary neopterin, pseudouridine, and creatinine allows a rapid evaluation of the activation state of cell-mediated immunity, and the stimulation of whole-body rRNA + tRNA turnover, associated with malignant growth. Urinary neopterin and pseudouridine concentrations in healthy subjects amounted to: 106.6 +/- 34.6 mumol/mol creatinine, and 19.6 +/- 5.2 mmol/mol creatinine (mean +/- SD), respectively. The increase of neopterin excretion in patients with haematological neoplasms ranged from 146% in Hodgkin's disease to 534% in non-Hodgkin's lymphoma, whereas the increase in cancer cases ranged from 95% in adenocarcinoma of the gaster to 741% in hepatocellular carcinoma. The changes in pseudouridine excretion were much less pronounced: 63% in non-Hodgkin's lymphoma and 120% in carcinoma of the urinary bladder. The correlation coefficient between neopterin and pseudouridine was relatively low (r = 0.43), although statistically significant (P < 0.01). In the case of several neoplasms e.g. Hodgkin's disease, polycythaemia vera, and adenocarcinoma of the gaster, neopterin was significantly elevated, whereas pseudouridine remained at a normal concentration. There was a positive relationship between the stage of the disease (primary focus, regional metastases, dissemination) and urinary concentration of pseudouridine in patients with adenocarcinoma of the large intestine. In the same patients the increase of neopterin excretion was noticed both in early and advanced stages, with the highest values in disseminated disease.

[Clinical usefulness of blood platelets cryopreserved in liquid nitrogen]. / Ocena klinicznej przydatnosci krwinek plytkowych kriokonserwowanych W temperaturze par azotu.

The hemostatic effectiveness of platelet concentrates cryopreserved in a vapor phase of liquid nitrogen were evaluated after transfusion of 14 concentrates to 6 patients. Transfusion of AB0 and Rh-compatible platelet concentrates elevated the number of circulated platelets in donors by about 24 G/L. The mean corrected count increment (C.I.) after 001 and 24 hours post transfusion was 14.694 and 7.735/microliters/m2/10(11) respectively. Decrease of haemorrhagic diathesis, and correction of bleeding time in all cases have been observed.

[Analysis of pregnancy, labor, child development and disease course in women with Hodgkin's disease]. / Analiza ciaz, porodów, urodzonych dzieci i przebiegu choroby u kobiet chorych na ziarnice zlosliwa.

Twenty pregnancies were observed in 16 women with Hodgkin's disease. During 3 pregnancies cytostatic treatment was given. In 6 cases the disease was diagnosed in pregnancy and the treatment was started after labour. Eleven pregnancies were diagnosed during remission, after a mean period of 4 years (range: 6 months to 8 years) from the completion of treatment. All pregnancies had a normal course and labours were not complicated. In 2 cases of successive pregnancies disease recurrence developed. in 1 case the active disease was exacerbated. Twenty healthy babies were born, in one low birth weight was noted. The development of all children in a period of 6 years, on average, was normal.

Preliminary evaluation of immunotherapy in patients with Hodgkin's disease.

The clinical course of 38 patients with Hodgkin's disease in the stage of remission was evaluated. The material consisted of two groups of patients: 1. submitted to immunotherapy and 2. control group. In 16 cases immunostimulation was performed with BCG vaccine, including four cases treated with BCG vaccine and levamisole and 3 patients were given levamisole only. In some patients, immunotherapy restored normal immunologic reactivity, as shown by the reversion of negative tests of delayed hypersensitivity. In all patients treated with levamisole caused normal blastic transformation of PHA-stimulated lymphocytes. In the group of patients treated with immunotherapy relapses of malignant lymphogranulomatosis were observed in 10.6% of cases, and in the control group--in 15.7%. The patients of both groups remain under continuous clinical surveillance.

Immune condition in patients with Hodgkin's disease.

In 40 cases of Hodgkin's disease (24 untreated patients and 16 patients in remission) the immunological humoral and cell-mediated competence was studied using test of hypersensitivity of DNCB and PPD, blastic transformation and the ability of 3H-DNA synthesis in lymphocytes stimulated with PHA and PWM, and in some cases, with PPD. In all patients the concentration of serum immunoglobulins was determined as well. Impairment of immunological reactivity was found in about 40% of patients, on the average, in various stages of the disease and during remissions following treatment with cytostatic agents and radiotherapy. The most frequent abnormality found in 52.5% of cases was impairment of blastic transformation of lymphocytes stimulated with PHA in vitro. In 60% of cases negative results of intradermal test with PPD and in 75% of patients the DNCB test was negative. No correlation could be found between impairment of the immune competence in this disease and the clinical stage and/or type of histological changes in lymph nodes.

N-acetyl-beta-glucosaminidase, beta-glucuronidase and beta-galactosidase in the leukocytes, serum and urine of healthy subjects and patients with immunocytoma.

The activity of GlcNAc-ase, GlcUA-ase and Gal-ase was determined in the leukocytes serum and urine of 23 patients with M. M., 11 patients with other neoplasms including 9 with lymphoreticular proliferative processes without associated monoclonal gammapathy. The range of normal enzyme activity was established in the investigations carried out in 45 health subjects. In the group of patients with M. M. without complications. normal activity of GlcNAc-ase, GlcUA-ase and Gal-ase was found in the leukocytes. In the group of patients with white blood cell count below 2.5 g/l and in cases after long-term treatment with Alkeran the activity of GlcNAc-ase and GlcUA-ase in the leukocytes was reduced. In the patients with M. M. the activity of GlcNAc-ase was raised in the serum and urine, and this activity was higher in cases with longer duration of the disease and more advanced pathological process. The patients with M-IgG protein showed a higher GlcNAc-ase activity in the serum and urine than those with protein M-IgA. A higher activity of GlcNAc-ase in the serum and urine than those with protein M-IgGK than in those with M-IgG gamma. In patients with M. M with renal complications the urinary activity of GlcNAc-ase was higher than in patients with M. M. without renal complications. In CLL the activity of GlcNAc-ase was found to be decreased in the leukocytes and raised in the urine. In patients with Hodgkin's disease the activity of the studied enzymes was raised in leukocytes while the results of their determinations in serum and urine were equivocal.

Studies on the biological functions of monoclonal immunoglobulins and their fragments.

Complement-binding ability of three isolated monoclonal proteins of IgG class, their Fab, and Fc fragments was analyzed (including tests for the presence of polymers, aggregated forms and immune complexes), and the influence of two monoclonal IgG lambda proteins on fibrinogen conversion to fibrin was determined. Two proteins--IgG1 lambda and IgG3K--bound small amounts of complement only when tested in native form, but failed to bind complement after thermal aggregation. Papain-digestion of these proteins revealed a significant ability of complement binding by Fc fragments. The third protein--M-IgG1 lambda--bound large amounts of complement when used in its native form, but after thermal aggregation this ability decreased. This protein differs in structure from monoclonal Ig described here. It was shown by the atypical elution pattern of papain digest of M-IgG1 lambda from CM-cellulose and by the anticoagulative activity of this protein. In control tests with polyclonal immunoglobulin complement-binding ability increased after thermal aggregation of the immunoglobulin, Fc fragments of the polyclonal immunoglobulin bound lower amounts of complement than whole molecules. As already mentioned, the activity of the factor inhibiting fibrinogen-to-fibrin conversion was observed in only one of two tested proteins M-IgG lambda. This activity was not connected selectively with Fab fragment. In identical concentrations polyclonal IgG had no effect on fibrinogen-to-fibrin conversion.

Lysozyme in the serum, urine and peripheral blood leukocytes in patients with immunocytoma.

Lysozyme activity was determined in the serum, urine and leukocytes of 53 patients with immunocytoma and 24 patients with lymphoproliferative syndromes without associated monoclonal gammapathy. In patients with multiple myeloma the frequency of low serum lysozyme activity and high leukocyte lysozyme activity was higher. In the cases with renal failure, lysozyme activity was raised in serum and urine, and the 24-hour urinary lysozyme excretion was increased. In 7 patients with increased urinary lysozyme excretion no clinical or laboratory evidence of renal complications was found. Relative monocytosis in peripheral blood was observed in half of the cases of multiple myeloma, and in these patients also in about half of the cases the lysozyme activity was raised in the leukocytes and urine, and the 24-hour urinary lysozyme excretion was increased. In patients with Hodgkin's disease, lymphosarcoma and chronic lymphatic leukemia the frequency of low serum lysozyme activity was increased.

Cell-mediated and humoral types of immunologic immunity in idiopathic pancytopenia.

In a majority of 34 patients (including 30 treated with androgens and glucocorticosteroids), the absolute lymphocyte count, percentage of the T population and its reactivity in vitro to PHA, PWM and sheep erythrocytes were normal. In one fourth of cases, serum levels of IgG and/or IgM classes of immunoglobulins were decreased. The deviations in levels of serum immunoglobulins, and in some patients in the lymphocyte count and in the T population and its reactivity to antigens were attributed to complex causes, including immunosuppressive treatment with adrenal glucocorticosteroids. It is suggested that indications for treatment with these hormones in cases of bone marrow aplasia with suppression of the lymphoid system should be restricted.

Lymphocyte response in in vitro cultures to some mitogens, and serum immunoglobulin levels in aged subjects.

Capacity of lympocytes for blastic transformation in in vitro cultures under the influence of PHA and PWM was studied in 40 subjects aged 20--60 years and in 43 aged 60--100 years. In the higher age group, in about 25% of cases, low percentages of blasts in cultures stimulated with PHA and PWM were observed. In 101 subjects aged 65--100 years, the mean level of IgA in serum was significantly higher compared with the 20--40-year age group. In some cases, levels of two or three immunoglobulin classes were raised. The unexplained changes in the reaction of lymphocytes to PHA and PWM and in levels of serum IgG were attributed to the old age of the subjects.