Differential IL-12 responsiveness of T cells but not of NK cells from tumor-bearing mice in IL-12-responsive versus -unresponsive tumor models

While IL-12 administration induces tumor regression through stimulating T cells in tumor-bearing mice, this IL-12 effect is observed in some but not all tumor models. The present study aimed to compare IL-12 responsiveness of T cells from tumor-bearing mice in IL-12-responsive (CSA1M and OV-HM) and -unresponsive (Meth A) tumor models. Tumor regression in IL-12-responsive tumor models required the participation of T cells, but not of NK1.1(+) cells. Because a NK1.1(+) cell population was the major producer of IFN-gamma, comparable levels of IFN-gamma production were induced in IL-12-responsive and -unresponsive tumor-bearing mice. This indicates that the amount of IFN-gamma produced in tumor-bearing individuals does not correlate with the anti-tumor efficacy of IL-12. In contrast, IL-12 responsiveness of T cells differed between the responsive and unresponsive models: purified T cells from CSA1M/OV-HM-bearing or Meth A-bearing mice exhibited high or low IL-12 responsiveness respectively, when evaluated by the amounts of IFN-gamma produced in response to IL-12. T cells from CSA1M- or OV-HM-bearing but not from Meth A-bearing mice exhibited enhanced levels of mRNA for the IL-12 receptor (IL-12R). These results indicate that a fundamental difference exists in IL-12 responsiveness of T cells between IL-12-responsive and -unresponsive tumor models, and that such a difference is associated with the expression of IL-12R on T cells.     

Large cell neuroendocrine carcinoma of the uterine cervix with cytogenetic analysis by comparative genomic hybridization: a case study

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a newly introduced category of the revised World Health Organization classification. We reported a case of cervical LCNEC with cytogenetic analysis by comparative genomic hybridization (CGH). The cervical tumor showed moderately increased mitotic activity (8-14 mitotic figures per 10 high-power fields) and focal necrosis, which made it problematic to differentiate from atypical carcinoid. CGH analysis failed to detect chromosome 11q loss that has been reported to be characteristic of pulmonary atypical carcinoids. Furthermore, chromosome 3q amplification, which has been detected frequently in pulmonary small cell carcinomas and LCNECs but not in pulmonary typical and atypical carcinoids, was the most remarkable chromosomal aberration. Although CGH reports are extremely rare in neuroendocrine tumors of the uterine cervix, specific chromosomal aberrations may be useful in their distinction.     

Behçet Disease and the HLA System

Seventy-three unrelated patients with Behçet disease together with 33 members of seven families with at least two patients per family were tissue typed for 26 antigens of the HLA system. The patients with the complete type of Behçet disease were found to have HLA-B5 more significanth than healthy individuals. Family studies suggest that the genes closely linked to HLA locus influence the degree of severity of Behçet disease.     

Adrenergic receptors in bovine retinal microvessels: presence of alpha 2- and beta- but not alpha 1-receptors

In bovine retinal microvessels, alpha 1, alpha 2- and beta-adrenergic receptors were characterized by binding assay, using [3H]prazosin, [3H]para-aminoclonidine and [125I]iodocyanopindolol as radioligands, respectively. The microvessels were purified from bovine eyes by differential centrifugation through a high concentration of bovine serum albumin followed by use of a glass bead filtration technique. In the preparation, specific binding sites for [3H]para-aminoclonidine and [125I]iodocyanopindolol were observed, whereas [3H]prazosin binding was not detected. The [3H]para-aminoclonidine binding sites localized to the microvessels were characterized by high affinity and saturability (KD: 173 +/- 9 pM; Bmax: 394 +/- 11 fmol/mg protein) as well as the [125I]iodocyanopindolol binding sites (KD: 20 +/- 3 pM; Bmax: 43 +/- 4 fmol/mg protein). Furthermore, the specificity of both binding sites was pharmacologically evaluated by measuring the inhibitory effects of various adrenergic reagents on binding. The existence of alpha 2- and beta-adrenergic receptors which were characterized by high affinity, saturability and stereospecificity, leads to the hypothesis that the retinal microcirculation is under neuronal control.     

Improvement of blood compatibility on cellulose hemodialysis membrane: IV. Phospholipid polymer bonded to the membrane surface

To improve the surface blood compatibility on a cellulose hemodialysis membrane, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with a phospholipid polar group were immobilized on the surface through covalent bonding. The MPC polymers had a carboxylic group, which can react with hydroxyl groups on the cellulose membrane, and were synthesized by conventional radical polymerization. The reaction between the MPC polymers and the cellulose membrane was carried out in a heterogeneous system using a condensation reagent. Surface analysis of the modified membrane by X-ray photoelectron spectroscopy revealed the immobilization of the MPC polymer on the surface. The mechanical strength and permeability for a solute of the membrane did not change even after the modification. The modified cellulose membrane was blood-compatible, as determined by the prevention of adhesion, deformation, and aggregation of platelets after contact with platelet-rich plasma. Based on these results, it is concluded that the MPC polymers may be a useful material for improving the blood compatibility of cellulose hemodialysis membranes.     

Preparation of nanoparticles composed with bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer

The poly(L-lactic acid) nanoparticles immobilized with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, which has excellent blood compatibility, were prepared by a solvent evaporation technique using the water-soluble amphiphilic MPC polymer as an emulsifier and a surface modifier. The diameter and zeta-potential of the obtained nanoparticles strongly depended on the concentration of the MPC polymer. When the nanoparticles were prepared in 1.0 mg/ml of an MPC polymer aqueous solution, the diameter was 221 nm which was determined by atomic force microscopy and dynamic light scattering measurements. The X-ray photoelectron spectroscopic analysis indicated that the phosphorylcholine groups of the MPC unit were located at the surface of the nanoparticles, that is, the MPC polymer was immobilized on the PLA particles and the surface zeta-potential was -2.5 mV. Various hydrophobic fluorescence probes could permeate through the MPC polymer layer and adsorb on the PLA surface. The amount of bovine serum albumin adsorbed on the nanoparticles was significantly smaller compared with that on the conventional polystyrene nanoparticles. It is suggested that the nanoparticles immobilized with the MPC polymer have the potential for use as both a novel drug carrier and diagnostic reagent which can come in contact with blood components.     

Angiosarcoma arising from skeletal haemangiomatosis in an atomic bomb survivor

The authors report a unique case in which an angiosarcoma arose from skeletal haemangiomatosis in a 72 year old man. This patient had a history of atomic bomb irradiation more than 50 years ago. Radiographically, the patient had multiple sclerotic foci of benign haemangiomas in the pelvis, the sacrum, and the left femur. The patient developed a high grade angiosarcoma in the left pubic bone. It is thought that atomic bomb irradiation played an important role in the development of the malignant lesion.     

Studies on complement-potentiated neutralizing antibodies (C'-PNAb) induced in rabbits inoculated with japanese encephalitis virus (JEV). I. The nature of C'-PNAb

The C'-PNAb induced by JEV grown in porcine kidney stable (PS) cells [JEV(PS)] inactivate not only the corresponding virus, hut also Western equine encephalitis (WEE), Eastern equine encephalitis (EEE), vesicular stomatitis (VS) and Sindbis viruses grown in PS cells or primary hamster kidney (HK) cell cultures in the presence of complement. The degree of complement-potentiated neutralizing (C'-PN) ability varies for each virus. The C'-PNAb do not, inactivate these viruses grown in mouse brain, even JEV. The C'-PN activity against viruses other than JEV(PS) is completely removed by absorption with the microsomal fraction of PS or HK cells, but not of mouse brain. The antibodies in fraction IgM induced by the microsomal fraction of PS or HK cells inactivate the viruses grown in PS cells to a different degree in the presence of complement, but not viruses grown in mouse brain. The activity of C'-PNAb against JEV(PS) is reduced to 2% of the original activity by absorption with sheep red cells. After absorption, the remaining C'-PNAb are not further reduced by absorption with the microsomal fraction of PS cells, nor do they inactivate the other viruses grown on PS cells. The early rabbit hemagglutination-inhibition (HI) antibodies in fraction IgM induced by JEV(PS) could not only inhibit hemagglutination with JE, WEE, EEE, and Sindbis viruses grown on PS cells in the absence of complement, but could also facilitate HI in the presence of complement. However, they could not inhibit hemagglutination with these viruses grown in mouse brain, in the presence or absence of complement. This activity of HI could also be removed by absorption with the microsomal fraction of PS cells. These findings suggest that C'-PNAb are induced by host cell components associated with the virus, and that the early HI antibodies in fraction IgM are the same entities as C'-PNAb.     

Clinical significance of IgG4 antibody determination in children against egg white, milk, soybean and Dermatophagoides farinae]

The measurement of IgE and IgG4 antibodies against egg white, milk, soybean and Dermatophagoides farinae was performed by FAST (fluorescence allergosorbent test) using 21 serum samples obtained from non-allergic children and 160 serum samples from atopic children with bronchial asthma and/or atopic dermatitis. Their antibody levels were evaluated for any association with disease severity and for clinical significance in establishing diagnosis. It was found that children with bronchial asthma showed lower levels of IgE antibodies against egg white, milk and soybean and higher levels of IgE antibodies against Dermatophagoides farinae compared with those of children with atopic dermatitis, while both groups showed higher levels of egg white and milk-specific IgG4 antibodies compared with non-allergic children. These IgE and IgG4 antibody levels revealed a tendency to correlate with disease severity in patients with atopic dermatitis, while this was not observed in patients with bronchial asthma. The contribution percentages of IgG4 antibody determination, together with IgE antibody determination, in retrieving causal allergens were 71% for egg white, 70% for milk and 48% for soybean allergy, implying their diagnostic value in establishing clinical diagnosis.