Functional CD4+T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus

Using two mAb, one specific to the alternative exon 6-dependentepitope of CD45 molecules(JH6.2) and one a natural thymocytotoxicautoantibody (NTA) with an unknown reactive epitope (NTA260),we subdivided splenic CD4⁺ T cells from 2-month-old BALB/c miceinto five phenotypically distinct subsets. CD45RC⁺NTA260^–(SI) cells were phenotypically analogous to CD4⁺ T cells predominatingin newborn mice and produced a significant amount of IL-2, butnot so IL-4, IL-10 or IFN- when stimulated with immobilizedanti-CD3 mAb in vitro. They appeared to consist mainly of naiveT_hP cells. The CD45RC⁺;NTA260⁺ (S II) subset also produced IL-2,but not other cytokines; however, the IL-2 levels produced weremuch higher than seen with the S I subset, thereby suggestingthe predominance of further maturated T_hP cells. The D45RC^–NTA260⁺(S III) subset mainly produced IL-4, IL-10, IFN- and less IL-2,and contained memory cells that helped the secondary antibodyresponse to a recall antigen, and hence contained T_h2 and probablya mixture of T_h0 and T_h1 cells. The CD45RC^–NTA260^–(S IV) subset was a poor responder to the immobilized anti-CD3mAb. The CD45RC^brightNTA260^dull(S V) subset consisted of a smallnumber of cells that were phenotypically analogous to activatedCD4⁺ T cells. While an age-associated decrease in the proportionof S I and less markedly in S II and in turn increase in S IIIsubsets of CD4⁺ T cells occurred in normal BALB/c mice, autoimmunedisease-prone (NZBxNZW)F₁ mice showed a marked age-associateddecrease in the proportion of not only S I, II but also IIIsubsets. As aged (NZBxNZW)F₁ mice carry CD4⁺ T helper cellsfor IgG anti-DNA antibody production, such age-associated polarizationto the S IV subset appears to be critical in the pathogeneslsof autoimmune disease in these mice.     

Free electron laser induces specific immobilization of heparin on polysulfone films

Covalent immobilization of heparin has been developed to reduce the amount of heparin administered systematically during long-term dialysis. Recently, it was doubted partially because of the complexion during immobilization process. In this study, we investigated a novel method for specific immobilization of heparin on polysulfone (PSF) via free electron laser (FEL) irradiation. Laser wavelengths of 6.18 or 6.31 microm, the typical absorption bands of carboxyl groups of heparin and aromatic rings in PSF, respectively, were chosen to irradiate the thin heparin membrane formed on PSF surfaces. The amount of heparin immobilized on PSF was measured by the toluidine blue method. The binding of heparin on PSF was analyzed by X-ray photoelectron spectroscopy (XPS). The immobilization of heparin resulted in a hydrophilic surface on which decreased platelet adhesion was observed. The efficiency differences, depending on laser wavelengths, were discussed from the point of view of structural and environmental differences of light-absorbing groups.     

Synthesis of polyetherurethanes containing L-serine dipeptide and their use as materials for biomedical films

Prepolymers, which were produced by the polyaddition reaction of polytetramethylene glycol (PTMG) or polyethylene glycol (PEG) and 4,4'-diphenylmethane diisocyanate (MDI) or hexamethylene diisocyanate (HMDI), were chain-extended with a linear dipeptide of L-serine (Z-Ser-Ser-OMe) or a cyclic dipeptide of L-serine [c-(Ser)2] to yield novel polyetherurethanes containing dipeptide segments. The relationship between the surface morphology and the biomedical properties of the film of the novel polyetherurethanes was investigated. The surface of PU(PTMG,Z-Ser-Ser-OMe,MDI) film was smooth, but fibrous structures were developed in the bulk of the film with increasing molecular weight of the PTMG segment. The antithrombogenicity of the film containing the low molecular weight PTMG segment was better than that of the usual polyetherurethane film without the dipeptide segments. The partial hydrolysis of the ester groups involved in the dipeptide segment improved the antithrombogenicity. In the surface and the bulk of PU[PTMG,c-(Ser)2,MDI] film, spherulite structures were developed when the molecular weight of the PTMG segment was high, while single crystals with a length of 3-4 microns were produced when the molecular weight of the PTMG segment was low. The antithrombogenicity of the film containing the high molecular weight PTMG segment was better than that of the usual polyetherurethane film without the dipeptide segments. PU(PTMG/PEG,Z-Ser-Ser-OMe,MDI) film and PU[PTMG/PEG,c-(Ser)2,MDI] film were permeated by uraemic toxins. The permeation was accelerated with increasing water content of the film and decreasing molecular weight of the solute. The oxygen permeability of the film of the polyetherurethane containing the linear or cyclic dipeptide segments was greater than that of polyetherurethane film which does not contain the dipeptide segments.     

Cross-correlation studies of movement-related cortical potentials during unilateral and bilateral muscle contractions in humans

A useful method of studying the degree of association between two signals of varying amplitude in the time domain is to use cross-correlation analysis. We applied this to the movement-related cortical potentials digitally filtered so as to eliminate the low frequency component before applying it during maximal unilateral left (UL L), unilateral right (UL R) and bilateral (BL) contractions in I I right-handed subjects. The recording electrode sites were over the right and left motor cortex areas (C3 and C4). The BL condition revealed higher cross-correlation levels of cortical activities between the two hemispheres than in UL L or UL R contraction [UL L, r = 0.68 (SEM 0.05); UL R, r = 0.73 (SEM 0.03); BL, r = 0.76 (SEM 0.02)]. The UL R revealed a positive phase difference [5 (SEM 2) ms] when the maximal cross-correlation coefficient was shown and UL L showed a negative phase difference [5 (SEM 3) ms]. However, BL revealed a smaller phase difference [2 (SEM 1) ms] than that for UL. It was concluded that during maximal BL contraction cortical cellular activities in both hemispheres was more synchronized in amplitude and time course compared with maximal UL contractions. Our data suggested that central common drive existed between the right and left motor areas during the maximal BL handgrip contractions and the amplitude of potentials of both hemispheres was modified by the interhemispheric inhibition mechanism as reported in other studies.     

Interleukin-2 receptor gene expression in kidney transplant recipients treated with cyclosporin A.

We examined the effects of cyclosporin A (CsA) administered in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to express IL-2 receptor (IL-2R) gene at the level of mRNA after mitogen stimulation in vitro. There were no differences in the percentage of IL-2R+ cells among the groups of normal individuals, azathioprine-prednisolone treated, and CsA-prednisolone-treated recipients, using FITC-labelled monoclonal anti-IL-2R antibody (anti-alpha chain): 40.3 +/- 10.1% and 62.8 +/- 11.1% of normal PBMC (n = 18), 37.0 +/- 9.3% and 61.7 +/- 5.8% of PBMC from azathioprine-prednisolone-treated recipients (n = 20), and 37.7 +/- 9.6% and 60.7 +/- 12.7% of PBMC from CsA-prednisolone-treated recipients (n = 20) expressed IL-2R after 24 h and 48 h of phytohaemagglutinin stimulation, respectively. However, in a study of Northern blotting using cDNA for IL-2R (anti-alpha chain specific), both the 3500 and 1400 bp families of IL-2R mRNA were remarkably decreased in PBMC from CsA-prednisolone-treated recipients compared with azathioprine-prednisolone-treated recipients and normal individuals. These studies demonstrated that CsA could inhibit IL-2R gene expression at the level of mRNA at physiological concentration.     

The number of proliferating cell nuclear antigen positive cells in endometriotic lesions differs from that in the endometrium

Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) was studied in the endometrium and in endometriotic lesions during the menstrual cycle and in post-menopausal patients. During the menstrual cycle, in the basal layer of the endometrium, an increase in the number of positive indices (PI) of PCNA was observed in epithelial cells from the menstrual phase. It reached a maximum in the proliferative phase and decreased in the secretory phase. However, no change was observed in the stromal cells of the basal layer. In the functional layer of the endometrium, the PI of the epithelial cells showed a high peak in the late proliferative phase, decreased sharply in the secretory phase and remained unchanged thereafter. The PI of the stromal cells in the functional layer showed two peaks, one in the late proliferative and the other in the mid and late secretory phase. In the endometriotic lesions, except for the proliferative phase, the number of PI was significantly higher than that of the corresponding endometrium and no significant changes were observed during the menstrual cycle. In post-menopausal endometriotic lesions, the number of PI was also higher than that of the corresponding endometrium. Thus the numbers of PI differed between the endometrium and endometriotic lesions in the same patients. These results imply that the endometriotic lesions are constantly more proliferative than the endometrium irrespective of the hormonal milieu during both the menstrual cycle and in a post-menopausal environment.     

Expression profiles and functional implications of p53-like transcription factors in thymic epithelial cell subtypes

In this study, we investigated the localization and functional significance of p53 tumor suppressor-like molecules, p63 and p73, in human thymic epithelial cells (TECs). Immunohistochemical studies showed particular distribution profiles of p63 and p73 in thymic epithelium, in which cortical TECs preferentially expressed p63 in their nuclei whereas subcapsular and medullary TECs expressed both p63 and p73 in their nuclei. The wide distribution of p63 in TECs was further suggested by studies using TECs of primary culture. In vitro studies using two human TEC lines demonstrated that p63 was capable of up-regulating intercellular adhesion molecule-1 (ICAM-1) and enhancing the production of IL-6 and IL-8. Moreover, in vitro studies also indicated that p73, but not p63, had the capacity to induce granulocyte macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) in the TEC lines. These findings suggest that p63 would regulate the cell adhesive property through ICAM-1/LFA-1 interaction and the production of IL-6 and IL-8, probably in all TEC subtypes. p73 in subcapslar and medullary TECs was suggested to play a role in the regulation of the production of GM-CSF and G-CSF, which might stimulate other stromal cells such as dendritic cells, macrophages and endothelial cells around these regions.     

Glutathione metabolism in red cell aging

Normal human red cells were centrifugally separated according to age by discontinuous density gradient of Percoll. Reduced glutathione (GSH), GSH stability and glucose-6-phosphate dehydrogenase (G6PD) activity in fractionated red cells decreased with age, while oxidized glutathione (GSSG) and methemoglobin (MetHb) increased with age.     

Maximal isometric force and neural activity during bilateral and unilateral elbow flexion in humans

We investigated maximal isometric force and electromyographic (EMG) activity of the biceps brachii muscle during rapid bilateral (BL) and unilateral (UL) elbow flexion in 11 right-handed subjects. The BL exhibited a deficit in force for both arms and more so for the right than the left arm during the rising phase of force generation. The EMG of the left biceps brachii muscle was similar during UL and BL, but for the right arm EMG was lower during BL than during UL for the rising phase of force generation. The BL to UL ratio of mean power frequency of the EMG was lower for the right than for the left arm. The data would suggest that the relatively small BL strength was associated with a equally small EMG and a shift to a lower mean power frequency especially for the fast motor units of the dominant muscle.     

Competition and physician-induced demand in a healthcare market with regulated price: evidence from Ghana

International Journal of Health Economics and Management - Using panel data of administrative claims spanning 36 months (2017–2019) and an instrumental variable method, this study...