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T cells expressing CD57 (a natural killer cell marker) with interferon-gamma (IFN-gamma) producing capacity increase under various conditions. CD57+ T cells are also present in the bronchoalveolar lavage fluid (BALF) of sarcoidosis, and several phenotypical and functional analyses of these cells have been reported. In the present study, BALF T cells obtained from 52 patients with sarcoidosis were classified further into CD4+CD57+ T cells, CD4+CD57- T cells, CD8+CD57+ T cells and CD8+CD57- T cells and their phenotypes and functional characteristics were assessed. Substantial proportions of these T cell subsets expressed natural killer cell markers CD161 and CD122. The biased expansion of Vbeta2 T cells was observed in both CD4+CD57+ T cells and CD4+CD57- T cells in BALF from most patients, while the expansion of other Vbeta T cells was also observed in some patients. Unexpectedly, the biased expansion of certain Vbeta T cells was also seen in either CD8+CD57+ T cells or CD8+CD57- T cells, while the expanded Vbeta T cells in CD8+ T cells differed substantially among individuals. BALF T cells showed a remarkably lower T cell receptor (TCR) intensity than that of peripheral blood T cells. Both CD8+ T cell subsets in BALF of sarcoidosis expressed the intracellular perforin/granzyme B, while all four subsets expressed intracellular IFN-gamma after in vitro activation, and CD4+ T cells, especially CD4+CD57+ T cells, expressed tumour necrosis factor-alpha. These findings indicate that CD57+ T cells as well as CD57- T cells in the BALF are phenotypically and functionally different from peripheral blood T cells and may play an important role in the Th1 dominant state and inflammation in pulmonary sarcoidosis.

Interleukin (IL)-4, IL-10, and IL-13 affect monocyte/macrophage functions including regulation of cytokine production. We analyzed the regulatory effects of these cytokines on cytokine production using a human monoblastic cell line, UG3. It is interesting that IL-10 up-regulated, whereas IL-4 and IL-13 down-regulated monocyte chemoattractant protein-1 (MCP-1) production by unstimulated UG3 cells. IL-10-induced expression of MCP-1 mRNA occurred without de novo protein synthesis at transcriptional and post-transcriptional levels. The enhancement of binding activity of nuclear factor Sp1 (Sp-1) and signal transducer and activators of transcription (STAT)1 and 3 but not nuclear factor kappaB (NF-kappaB) was associated with this IL-10-induced MCP-1 expression. Furthermore, IL-10 suppressed lipopolysaccharide (LPS)-induced NF-kappaB binding but not Sp-1. The present results suggest IL-10 has two contrasting actions on the MCP-1 production of monocytes/macrophages, between the resting and activated conditions. The combination of activated Sp-1 and STATs is important for IL-10-induced MCP-1 expression in resting monocytes/macrophages, and the inhibition of LPS-induced NF-kappaB binding is crucial for down-regulation of MCP-1 by IL-10 in stimulated monocytes/macrophages.

A retrospective case study of 33 Guillain-Barré syndrome (GBS) patients with the antibody to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a) was made to investigate the clinical features of GBS with this antibody. Patients were classified into three groups: (i) 25 with IgG antibody (group G, titre >/= 1 : 40); (ii) 16 with high-titre IgG antibody (group G-high, titre >/=1:320; selected from group G patients), and (iii) eight with IgM antibody but without elevation of IgG (group M, normal range <1:40 for both IgM and IgG). The control group consisted of 72 GBS patients without anti-GalNAc-GD1a antibody. Compared with the control group, the G-high and G group patients were characterized as having had antecedent gastrointestinal infection (87% and 72% versus 31%, both P < 0.001), uncommon cranial nerve involvement (19% and 36% versus 54%, P = 0.02 and 0.2, respectively), distal-dominant weakness (94% and 68% versus 36%, P < 0.001 and P = 0.01, respectively) and no sensory signs (81% and 60% versus 25%, P < 0.001 and P = 0.003, respectively). Electrophysiological findings indicative of axonal dysfunction were significantly more common in the G-high and G group patients (63% and 52% versus 14%, both P < 0.001). The pure motor variant that showed neither sensory signs nor abnormalities in sensory conduction studies was also more frequent in these groups (44% and 32% versus 9%, both P < 0.001). IgG anti-GalNAc-GD1a antibody may be a marker of the pure motor and the axonal variants of GBS, and therefore it, as well as anti-GM1 antibody, must be investigated in these forms in order to diagnose and understand the variants. By contrast, mild weakness, frequent facial palsy (75%) and a high incidence of IgM anti-GM2 antibody reactivity (88%) were characteristic of group M, indicating that the GBS in that group resulted from a different immune mechanism from that in the G group.

Osteoclastogenesis inhibitory factor (OCIF), also termed as osteoprotegerin (OPG), is a soluble member of the tumor necrosis factor receptor family. Although OCIF/OPG is shown to inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo, its effect on serum calcium level remains to be determined. In this study we examined the acute effect of OCIF on thyroparathyroidectomized rats whose serum calcium concentrations were raised either by exogenous PTH or 1,25-(OH)2D3. When OCIF was administered at the start of PTH infusion, it attenuated the initial rise in serum calcium. When OCIF was administered into rats with established hypercalcemia, it decreased serum calcium rapidly (within 2 hr) and dramatically. OCIF did not increase urinary calcium excretion. These findings, especially the rapid onset of its hypocalcemic effect, suggest that OCIF not only inhibits the formation of osteoclasts but also affects the function and/or survival of mature osteoclasts at doses used in this study.

A 48-year-old patient was admitted to our hospital for leukocytosis. The blast cells were positive for peroxidase and he was tentatively diagnosed as acute myeloid leukemia according to the French-American-British criteria. By flow cytometry, the bone marrow cells were positive for CD10, CD13, CD33 and HLA-DR, but two-color analysis revealed that most of the CD13- and CD33-positive cells did not express CD10. The marrow cells had Philadelphia chromosome with no additional abnormalities. Major bcr-abl fusion gene was observed by the reverse transcriptase-polymerase chain reaction method. Southern blot analysis disclosed rearrangement of both immunoglobulin heavy chain and T-cell receptor beta chain genes. He received combined chemotherapy for myeloid lineage and lymphoid lineage, but the response was quite poor. He died 64 days after admission due to pulmonary bleeding. Although the association of Ph1 with multilineage differentiation is unclear, our case has significant implication for further investigation of the relationship between Ph1-positive cells and lineage selection.

The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2- release were investigated in neutrophils from 14 patients with myelodysplastic syndromes (MDS). The O2(-)-releasing capacity in MDS neutrophils varied from patient to patient. As compared with normal neutrophils, the O2(-)-releasing capacity in MDS neutrophils was increased in 9/14 patients, normal in three patients and decreased in two patients. There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The priming of neutrophils by rhG-CSF was not observed in five patients, whereas rhGM-CSF primed neutrophils from all patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in each patient. The intravenous administration of rhG-CSF (300 micrograms/body) to two MDS patients showed an increase in the peripheral blood neutrophil count and enhancement of neutrophil O2- release. These findings demonstrate that the neutrophil O2(-)-releasing capacity in MDS varies from patient to patient and is not always impaired, and that rhGM-CSF is able to prime neutrophils which never respond to rhG-CSF.

Three concentrations of tetradecane and liquid paraffin were applied daily for 4 weeks to the external ear skin of rabbits, and the average diameter of the follicular lesions was measured under the Leitz MZ surface microscope. These observations showed that the increase in the size of follicular lesions with tetradecane was dose-dependent and the maximum diameter was reached on the 14th day. Serial biopsies were also taken for routine histology, and undiluted tetradecane was shown to produce follicular hyperkeratosis, microcomedones, closed comedones and open comedones. A good correlation was obtained between the surface observations and the histological findings. The surface microscope provides a simple and convenient in vivo method for evaluating comedo formation.

In the preceding papers, we showed that one of the two complementar factors of polypeptide chain elongation factor 1 (EF-1) from pig liver, EF-1alpha, functionally corresponds to bacterial EF-Tu (Nagata, S., Iwasaki, K., and Kaziro, Y. (1976) Arch. Biochem. Biophys. 172, 168), while the other, EF-1betagamma, as well as one of its subunits, EF-1beta, corresponds to bacterial EF-Ts (Motoyoshi, K. and Iwasaki, K. (1977) J. Biochem. 82, 703). Therefore, the interaction between EF-1alpha and EF-1 betagamma or EF-1beta was was examined and the following results were obtained. i) EF-1betagamma catalytically promoted the exchange of [14C]GDP bound to EF-1alpha with exogenous [3H]GDP. ii). In the absence of the exogenous guanine nucleotide, EF-1betagamma as well as EF-1beta could displace GDP bound to EF-1alpha to form an EF-1alpha.EF-1betagamma as well as an EF-1alpha.EF-1beta complex. iii) The occurrence of EF-1alpha.EF-1betagamma and EF-1alpha.EF-1beta complexes was demonstrated by gel filtration on Sephadex G-150. These results strongly indicate that the mechanism of the action of EF-1betagamma or EF-1beta in converting EF-1alpha.GDP into EF-1alpha.GTP is analogous to bacterial EF-Ts, and the reaction is accomplished by the following reactions; EF-1alpha.GDP + EF-1betagamma (or EF-1beta) in equilibrium EF-1alpha.EF-1betagamma (or EF-1beta) + GDP; EF-1alpha.EF-1beta (or EF-1beta) + GTP IN EQUILIBRIUM EF-1alpha.GTP + EF-1betagamma (or EF-1beta).

The comedogenicity of UVA-irradiated and non-irradiated substances (squalene, oleic acid, tetradecane, isopropyl myristate, squalane and liquid paraffin) was evaluated by surface microscopy and histological examination after treating the ventral skin of rabbit ears with these substances. The lipid peroxide levels of these substances were also measured. Squalene itself was scarcely comedogenic but squalene peroxides were highly comedogenic. Both oleic acid and its peroxides were able to induce fairly large comedones and there was a good correlation between the lipid peroxide levels and the size of the comedones. The specimens biopsied from these comedones showed marked hyperplasia and hyperkeratosis of the epithelium in the follicular infundibulum and marked proliferation of the sebaceous glands. Although free fatty acids might play a role in the pathogenesis of acne, it is proposed that squalene and free fatty acids in sebum may be less comedogenic than their peroxides.