Changes in Cell Characteristics Due to Culture Conditions in Cell Lines From Human Small Cell Lung Cancer

Eight cultured cell lines were established from human smallcell lung cancers. Every cell line showed the morphologicaland biochemical characteristics of small cell cancer. Changesin cell characteristics were observed in many of these celllines when culture conditions were changed: "oat cell type"changed to "intermediate cell type" and vice versa when serum-freemedium was changed to serum-supplemented medium; a deficiencyof vitamin A in the medium caused a change to squamous cellsand vice versa; and a tumor promoter (teleocidin B) enhancedthe adherence of these cells to the surface of plastic culturedishes. These findings provide evidence that many small celllung cancer cell lines can change their morphology with changesin the environment of the cells.     

RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF CYP2E1 AND ALDH2, AND POSSIBLE SUSCEPTIBILITY TO ALCOHOLISM

In 45 healthy Japanese volunteers, it was found that personsheterozygous for ALDH2 (ALDH2^*1/ALDH2^*2), and also either heterozygousor mutant homozygous for CYP2E1 (C₂/C₂ or C₁/C₂ can drink muchmore alcohol, even with (slight) flushing, than persons heterozygousfor ALDH2 (ALDH2^*1/ALDH2^*2) and normal homozygous for CYP2E1(C₁/C₁)     

Immunogenic Properties of Structurally Modified Human Tissue Plasminogen Activators in Chimpanzees and Mice

Immunogenic properties of second generation human tissue plasminogenactivator (tPA) derivatives were examined in chimpanzee andmouse systems. Five species of modified tPAs (mtPAs) (designated2660, 2663, 2810, 8000, and 9200), recombinant native tPA orbovine serum albumin (BSA) as a positive control were subcutaneouslyinjected nine times at suitable intervals into chimpanzees,genetically the closest species to man. These animals were testedfor antigen(Ag)-specific antibodies to the corresponding proteinsby means of enzyme-linked immunosorbent assay and Western blotanalysis. Neither 9200, one of the five mtPAs tested, nor tPAwas immunogenic, although BSA and the other four mtPAs wereimmunogenic under these conditions. Thus, an antigenic determinant was not exposed by the modification on 9200 and thismodified tPA is expected not to be immunogenic in humans. Inthe mouse studies, mice were immunized with mtPAs. Serum sam-piesfrom these animals were tested for antibodies to the mtPAs whichdid not concomitantly recognize native tPA by immune ad sorptionof the antibodies to tPA. The amount of such antibodies alterthe elimination of native tPA-reactive antibodies was littleor none when the serum samples from 9200 and from the othermtPAs, except 8000, were tested. Taking into consideration theresults of the chimpanzee studies, it can be concluded thatAg-specific antibodies are dominantly produced to unchangedepitopes present in modified proteins in the mouse system, inwhich the native protein is immunogenic. These results suggestthat the chimpanzee model should be useful to predict immunogenicityof second generation recombinant proteins in man, while themouse system adopted by us, which determines the newly generatedepitopes of the modified proteins, is not sufficient.     

Reflex sympathetic dystrophy in childhood: A case report

A case report is presented of a 15-year-old girl with reflex sympathetic dystrophy (RSD). She was referred to hospital because of left upper limb pain. Her left upper limb was cold, edematous and blue with a limited active range of movement. The serum concentration of noradrenaline was lower on the painful side than on the healthy side, and neurotropin, which has an antinociceptive effect to hyperalgesia, was clearly effective. Early diagnosis and management is essential in the treatment of RSD and administration of neurotropin is a useful and non-invasive treatment without severe adverse effects.     

A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders

A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) has been established to estimate serum thrombopoietin (TPO) concentrations in healthy volunteers and patients with haemopoietic disorders. The ELISA uses a mouse monoclonal antibody (Ab) as the capture Ab and a biotinylated rabbit polyclonal Ab as the detector. The ELISA was reproducible, highly sensitive and specific for human TPO. The coefficients of intra- and inter-assay variation were from 3.0% to 4.9% and from 5.9% to 6.1%, respectively. The quantitative limit of the ELISA was 0.09 fmol/ml in serum. The quantitative limit was lower than the normal level. The dose–response curves of serum samples from healthy volunteers and patients with haemopoietic disorders were parallel to the standard curves. The ELISA did not cross-react with a variety of blood components and cytokines to produce false-positive results.
The serum TPO concentrations from 29 normal males and 21 females were 0.79 ± 0.35 and 0.70 ± 0.26 fmol/ml, respectively. Serum TPO levels in patients with aplastic anaemia (AA), acute lymphocytic leukaemia (ALL) and essential thrombocythaemia (ET) were measured using the ELISA. The serum TPO levels in the patients with ET ( n  = 6, 2.80 ± 1.55 fmol/ml) were higher than the normal level. The patients with AA ( n  = 7, 18.53 ± 12.37 fmol/ml) and ALL ( n  = 5, 10.36 ± 5.57 fmol/ml) had significantly higher serum TPO levels than normal individuals. These results indicate that the ELISA specific to TPO should prove useful in measuring the TPO concentration in serum samples.     

Infectious mononucleosis in Japan: Comparison with acute viral hepatitis type A

In order to clarify the characteristics of infectious mononucleosis hepatitis (IMH) in Japan, 20 cases with IMH treated at Kamo Hospital during the past 6 years (Group I) were analysed in comparison with cases of acute viral hepatitis, especially type A. The test for heterophil antibody was positive in only two cases. During the same period 209 cases were treated for acute viral hepatitis (type A: 77 cases = Group A; type B: 61 cases; type non-A, non-B: 71 cases). In Group I the common clinical symptoms and signs were headache, sore throat and lymph node swelling; jaundice was not as common as in Group A. GOT and GPT activities increased moderately in the acute stage, but they were significantly lower than those in Group A. LDH, AP, GGT and LAP activities were disproportionately higher to GPT activity in Group I. Liver biopsy in the convalescent stage showed that lipofuscin deposition and sinusoidal mononuclear cell infiltration were more prominent in Group I, while sinusoidal neutrocyte infiltration and focal necrosis at periportal areas were more common in Group A. Differential diagnosis of the two diseases could be made using these clinical features and histological findings. However, immunological differentiation is required for specific diagnosis because some features such as fever, prolonged elevation of thymol turbidity test, atypical lymphocytes in peripheral blod and predilection for young people were observed in both groups. Furthermore, the present study indicated that IMH is no longer rare and most cases do not demonstrate heterophil antibody in Japan.