Genotoxicity testing of cigarette-smoke condensate in the SCE and HGPRT assays with V79 Chinese hamster cells

The genotoxicity of cigarette-smoke condensate (CSC) was investigated using V79 Chinese hamster fibroblasts in the sister-chromatid exchange (SCE) and HGPRT (hypoxanthine-guanine-phosphoribosyl-transferase) tests. CSC was negative in the SCE test both with and without metabolic activation (co-cultivation with chick-embryo primary hepatocytes). In the HGPRT test no direct mutagenicity of CSC was observed but after metabolic activation there was a considerable increase in the number of mutants. Comparison of different metabolizing systems showed that non-induced chick hepatocytes, liver homogenate from non-induced chick embryos and liver homogenate from rats pretreated with Aroclor 1254 generated similar numbers of mutants in cells treated with CSC. In addition the capacity of CSC to inhibit metabolic co-operation between V79 cells was studied. A dose-related increase in the inhibition of metabolic co-operation was observed.     

A comparative study of immunological and cytochemical profiles between adult and childhood acute lymphoblastic leukemias (ALLs): Heterogeneity in adult common ALL

To investigate the biological differences between adult and childhood acute lymphoblastic leukemia (ALL), leukemic blasts from 33 patients with ALL (22 adults and 11 children) and from 11 patients in the lymphoid crisis of chronic myeloid leukemia (CML) were studied using cytochemical and immunological markers and also by the outcome of their treatment. The cytochemical studies showed that blasts from seven of the adult ALL patients were dense-granular-positive (DG-positive) for β-glucuronidase, whereas the blasts from the children were negative except for one (with T-ALL). In the adults with common ALL (cALL), survival of patients DG-positive for this enzyme were significantly shorter than that of eight patients with a scattered granular pattern (p <0.05). The mean ratio between the percentage of blasts positive for cALL antigen (cALLA) to that of blasts positive for terminal deoxynucleotidyl transferase (TdT) in the adult group with CALL (0.6 ± 0.3) was significantly lower (p < 0.01) than in the group of children with cALL (1.1 ± 0.2) or in the lymphoid-crisis group (1.5 ± 1.0). These findings indicate that adult cALL consists of two distinct subpopulations, one with less differentiated phenotype (cALL^?/TdT⁺) and the other with more (cALL⁺/TdT⁺). In contrast, the blast cells in childhood cALL and some patients in lymphoid crisis had a relatively homogeneous population with the latter phenotypes. The results suggest that the clonotypic cells in adult ALL, particularly in cALL, appear to be more immature than those in childhood ALL. The β-glucuronidase patterns indicate a further heterogeneity in adult ALL.     

NEONATAL THYROTOXICOSIS

Abstract. Neonatal thyrotoxicosis is a transient hyperthyroidism in infants of mothers with current or previous thyrotoxicosis. The pathogenesis has been accepted to be placental transfer of maternal thyroid stimulating immunoglobulins. Of two siblings from a previous thyrotoxic mother the first had marked symptoms of thyrotoxicosis but during the second pregnancy antithyroid treatment was given to the mother and though the child had high levels of thyroid hormones for 6 weeks it had only minimal symptoms of thyrotoxicosis.     

Humoral immunodeficiency to bacterial antigens in patients with juvenile onset diabetes mellitus

Summary Humoral immunity to bacterial antigens was tested in 49 tissue typed patients with juvenile onset diabetes mellitus (JOD) and in 50 healthy controls. The number of patients with agglutinins to E. coli and staphyloccoci was significantly lower compared to controls (p<0.001, p<0.01 respectively). Missing antibody formation to pertussis and diphtheria toxoid could also be detected in a higher percentage of JOD patients than of controls (p < 0.05; p 0.05, respectively). By contrast heteroagglutinins to sheep and rabbit erythrocytes were found in similiar proportion in both groups and the values of immunoglobulin serum concentrations showed no difference between patients and controls. In addition no correlation between antibody formation and genes of the HLA complex was found. It is suggested that the severely reduced agglutinin formation to bacterial antigens might be partly responsible for susceptibility to bacterial infections in juvenile diabetics.National Blood Group Reference Laboratory (WHO), National Tissue Typing Reference Laboratory (Council of Europe).     

Characterization of malignant cell populations in MNU-induced leukaemia of mice.

A surface marker analysis was found to be of value in classifying leukaemias of poorly differentiated blasts induced by MNU. Thy-1+ve(T cell) lymphoma commonly arose in intact animals with the thymus frequently, though not invariably, enlarged. Thy-1?ve, Ig—ve leukaemias arose in a low percentage of intact mice and in $\text{8}\text{16}$ leukaemias of thymectomized mice that were tested. These “markerless” leukaemias remain uncharacterized. Of the remaining leukaemias that developed in thymectomized mice, $\text{4}\text{16}$ were Ig+ve (or B cell) lymphomas and $\text{4}\text{16}$ showed low-intensity staining for both Thy-1 and Ig. The mechanism of thymic involvement in MNU-leukaemogenesis is discussed. Leukaemias of intact and thymectomized mice do not appear to arise from a common target cell since Thy-1+ve leukaemias rarely arose in thymectomized mice given implants of neonatal thymus tissue shortly after MNU-treatment. In fact, MNU-induced thymic lymphoma arises from an intra-thymic target population.     

Role of carnitine in promoting the effect of antidiabetic biguanides on hepatic ketogenesis.

Effects of biguanides on carnitine content of rat and guinea pig liver and on capacity of rat liver slices for ketogenesis were studied. In acute experiments, fed. 24-hour and 48-hour fasted male rats were given a single dose ofbuformin and the carnitine and acetylearnitine level in the tissues were determined 1 or 3 hr afterwards. The same was performed on fed guinea pigs. In all the 1-hr groups we found an increase ranging from 30 to 50 per cent in hepatic carnitine level. In chronic experiments rats were treated with buformin or metformin for 6 days. The carnitine content, carnitine acetyltransferase and carnitine palmitoyltransferase activities were determined. The respective carnitine levels in the buformin- and metformin-treated groups were 4 times and 2.5 times the control value expressed on a per gram basis. In addition, carnitine acetyltransferase activity, given as mU/mg mitochondrial protein, increased 2-fold in the buformin-treated group. The increase in carnitine content strongly suggests that liver has enhanced capacity for oxidation of fatty acids and consequently for production of ketone bodies. The latter has been verified in the chronic experiments by the following observations: (1) The buformin administration increased the total ketone body content of the freeze-clamped liver specimens to 210 per cent of the control value. The calculated mitochondrial NAD⁺/NADH ratio was reduced from 10.6 to 5.96 in the same specimens. (2) the liver slices from treated animals formed 30–40 per cent more ketone bodies than those from control ones during the 30-min and 60-min incubations. (3) The ketone body associated radioactivity deriving from Na-[1¹⁴-C] palmitate accounted for 90.5 per cent of water soluble radioactivity in slices from treated animals, whereas it accounted for 66.8 per cent in slices from control ones.     

Characterization of circulating immune complexes by nephelometry in acute leukaemia

Summary Circulating immune complexes were isolated from 15 patients with acute leukaemia and 13 healthy blood donors by PEG precipitation. These were analysed according to their IgG, IgM and C4 content by optical rate nephelometry. Immune complexes of leukaemic patients contained higher amounts of IgM as compared to those from normal subjects. The clinical relevance of IgM containing immune complexes in leukaemia is discussed.     

Surface Immunoglobulin of Human Lymphocytes

Using ferritin as surface marker, the localization of the surface immunoglobulin (Ig) was studied on peripheral lymphocytes from normal human individuals and patients with macroglobulinaemia Waldenström by scanning immunoelectron microscopy. Normal IgG-, IgM-lymphocytes and pathological IgM-lymphocytes were then compared with regard to their topographical differences. In all cells examined, IgG- and IgM-conjugated ferritin particles were detected all over the cell surface, but the distribution of the former on the normal IgG-lymphocytes was slightly more diffuse than that of the latter on the normal and pathological IgM-lymphocytes. Furthermore, in the pathological IgM-lymphocytes, the clustered IgM-conjugated ferritin particles were found in great number on the microvilli. Normal IgG-lymphocytes were almost always characterized by short rod-like microvilli standing densely and vertically on the cell surface. Some of normal IgM-lymphocytes had a similar appearance to those of normal IgG-lymphocytes (type A) but others (type B) had tilted rod-like microvilli or wide plate-like processes on their surface. As for IgM-lymphocytes of macroglobulinaemia, most lymphocytes had tilted rod-like microvilli and wide plate-like processes similar to type B, whereas a minor population of the pathological lymphocytes carried long, thin rod-like microvilli standing vertically on the surface.     

Determination of antibodies and non-specific immunoglobulins produced by single cells

To determine whether one cell simultaneously produces antibodies and non-specific immunoglobulins (nIg), spleen cells from mice immunized twice with SRBC were cultivated on membrane filters, firstly on the layer of native SRBC in agarose and then on the layer of SRBC sensitized with anti-mouse IgG antibodies. A specific immunoadsorbent, eliminating all anti-SRBC antibodies, was placed between the filters with spleen cells and sensitized SRBC. By comparing the location of indirect and reverse plaques (i.e. the location of cells producing antibodies to SRBC and nIg) it was shown that antibody-forming cells do not synthesize nIg.     

有关小儿癫痫免疫问题的临床研究

研究目的 探讨小儿癫痫与免疫的关系以及免疫制剂对小儿癫痫的治疗效果。 研究方法 59例癫痫患儿,男37例,女22例。采用单向免疫扩散法检测血中IgG、IgM、IgA和补体C_3、C_4。用人丙种球蛋白肌注治疗小儿癫痫。 研究结果 71.19％的患儿IgA<1.40g/L,30.15％的患者 IgG<8.og/L,部分患儿存在着低补体血症。采用人丙种球蛋白治疗小儿癫痫,总有效率达81.36％。 研究结论 小儿癫痛患者存在着免疫异常,免疫异常可能是小儿癫痫发病的重要原因之一。用人丙种球蛋白治疗小儿癫痫有效。