High frequencies of identical T-cell clonotypes accumulating in different areas of synovial lesions of rheumatoid arthritis patients.
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Arthritis, Rheumatoid↗
Biomedical subjects
Y Mizushima
Publications and source records attributed to Y Mizushima.
Accumulation of distinct T cell clonotypes in human solid tumors.
Tumor-infiltrating lymphocytes (TIL) have been described in a variety of human solid tumors. It is unknown whether such T cells are nonspecific inflammatory cells or a subset of specific host immune responses. To examine this question, we have analyzed the clonotypes of TCR beta-chain messages expressed in TIL, draining lymph nodes, and PBL of 10 patients with uterine or ovarian tumors. We report here that TIL bears distinct T cell clonotype accumulations only in patients without obvious metastasis. In contrast, accumulations of clonally expanded T cells were also found in lymph nodes and PBL of patients with metastatic cancer. The numbers and locations of the accumulated T cell clonotypes seemed to correlate with the stage of tumor invasion and the degree of metastasis. These data support the existence of Ag-driven immune responses to solid tumors in vivo.
Adenocarcinoma↗
Excessive function of peripheral blood neutrophils from patients with Behçet's disease and from HLA-B51 transgenic mice.
OBJECTIVE: To elucidate the role played by HLA-B51 in the neutrophil hyperfunction of Behçet's disease, we determined the superoxide production by purified peripheral blood neutrophils from Behçet's disease patients, from HLA-B51 positive healthy individuals, and from HLA-B51 transgenic mice. METHODS: Neutrophil function was evaluated by flow cytometric analysis, detecting the conversion of 2',7'-dichlorofluorescin diacetate into dichloroflurescein, induced by superoxide in the neutrophils. RESULTS: A significant correlation between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, was observed in humans. FMLP-stimulated neutrophils (without in vitro priming) from HLA-B51 transgenic mice, but not those from HLA-B35 transgenic mice or from nontransgenic mice, produced substantial amounts of superoxide. CONCLUSION: The HLA-B51 molecule itself may be responsible, at least in part, for neutrophil hyperfunction in Behçet's disease.
Animals↗
Streptococcus oralis previously identified as uncommon 'Streptococcus sanguis' in Behçet's disease.
The relation between the biochemical and serological properties of 'Streptococcus sanguis' was studied to characterize the strains isolated from dental plaque of patients with Behçet's disease and controls. Seven reference and 100 clinical strains preserved by the Behçet's Disease Research Committee of Japan were identified using established criteria and differentiated with antisera against Strep. oralis ATCC 10557, Strep. sanguis ATCC 10556 and 'Strep. sanguis' ST7, compatible with the criteria. Uncommon serovars (serotypes) KTH-1 (= ATCC 49298), KTH-2 (= ATCC 49296), KTH-3 (= ATCC KTH-4 (= ATCC 49297) and B220 (serovar KTH-1) with both IgA1 protease and neuraminidase (sialidase) were identified as Strep. oralis, whereas common serovars ST3 with IgA1 protease alone and ST7 without both enzymes were identified as Strep. sanguis and Strep. gordonii, respectively. Isolates previously ranked as uncommon serovars were identified as Strep. oralis, whereas the rest ranked as common serovars were identified as the same species as those of the grouping strains. A soft-agar technique was available for species identification except for Strep. oralis serovar KTH-1 reacting with the antiserum against Strep. gordonii ST7. The frequency of isolation of Strep. oralis was higher in Behçet's disease (52%) than in controls (38%), but no difference was observed between the properties of the two groups of isolates. Strep. oralis virulence factors may be involved in breach the mucosal barrier in patients with specific reactivity to these antigens and inducing Behçet's disease.
Behcet Syndrome↗
Induction of differentiation into monocyte/macrophage cell lineage of a human eosinophilic leukaemia cell line EoL-1 by simultaneous stimulation with tumour necrosis factor-alpha and interferon-gamma.
Human myeloid leukaemia cell lines have been shown to differentiate into distinct cell lineages in vitro in response to several differentiation-inducing agents. A human eosinophilic leukaemia cell line, EoL-1, has been shown to differentiate into mature eosinophilic granulocytes by treatment with the culture supernatant of a human T-cell line, HIL-3. In this study we have studied whether the EoL-1 cell line has potential to differentiate into cell lineage other than eosinophils. We found that EoL-1 cells cultured in the presence of tumour necrosis factor (TNF)-alpha (10 u/ml) and interferon (IFN)-gamma (1000 u/ml) for 2-4 d differentiated into macrophage-like cells in morphology, and expressed CD14 antigen on their cell surface. It is possible that the small subpopulation of EoL-1 cells which contains non-specific esterase (NSE) activity may be preferentially differentiated by TNF-alpha and IFN-gamma. To clarify this issue, we have cloned the EoL-1 cell line and obtained NSE negative and positive sublines. Both EoL-1 sublines differentiated into monocyte/macrophage-like cells, because: (a) EoL-1 sublines were induced to express CD14 antigen, and (b) they attached firmly to the plastic wells; (c) after differentiation they became strongly positive for NSE staining, and secreted TNF-alpha in response to the stimulation with lipopolysaccharide; and (d) they exhibited potent phagocytic activity. Therefore, we found that the EoL-1 cell line has the ability to differentiate not only into mature eosinophilic cells but also into monocyte/macrophage cell lineage, suggesting that EoL-1 cells represent immature cells with ability to differentiate into multiple cell lineages.
CD11 Antigens↗
Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE).
The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.
Adult↗
Recognition of a unique peptide epitope of the mycobacterial and human heat shock protein 65-60 antigen by T cells of patients with recurrent oral ulcers.
T cell epitopes of the 65-kD heat shock protein (hsp) were investigated in patients with recurrent oral ulcers (ROU). Peripheral blood mononuclear cells were stimulated with overlapping synthetic peptide (15ers), derived from the sequence of the 65-kD hsp of Mycobacterium tuberculosis. Specific lymphoproliferative responses were stimulated only with peptide 91-105 in ROU, compared with healthy or disease controls (P < 0.01). This was confirmed by studying 760 short term cell lines generated with the 65-kD hsp and then stimulated with the peptides. The frequency of short term cells lines responding to peptide 91-105 in ROU was significantly greater than in healthy (P < 0.0001) or disease controls (P < 0.01). A comparative investigation with the homologous human 60-kD hsp peptide 116-130 also showed significantly greater lymphoproliferative responses in ROU than in healthy (P < 0.01) or disease controls (P < 0.001). The potential involvement of the T cell epitope 91-105 in the pathogenesis of ROU is supported by finding a significant increase in the lymphoproliferative responses stimulated with peptide 91-105 during the stage of ulceration, compared with remission in 9/11 patients studied sequentially (P < 0.05). The results suggest that oral ulceration might be initiated by the microbial hsp peptide 91-105 stimulating the mucosal Langerhans cells, which may generate autoreactive T cell clones primed to the homologous peptide 116-130.
Adult↗
Periarticular osteopenia in adjuvant induced arthritis: role of interleukin-1 in decreased osteogenic and increased resorptive potential of bone marrow cells.
OBJECTIVE: To clarify the local osteogenic and bone resorptive potential of periarticular bone in adjuvant induced arthritis (AIA). METHODS: Formation of fibroblast colony forming units (FCFU; osteogenic precursor cells) and osteoclast-like cells in bone marrow culture was studied in AIA rats. Osteoclast-inducing activity in the AIA rat bone marrow was assayed by the addition of the marrow supernatant from rats with AIA to control cultures. Bone mineral density was determined by dual x ray absorptiometry. RESULTS: Marrow from AIA rats and that from animals receiving recombinant human interleukin-1 (IL-1) beta for seven days grew significantly fewer FCFU than control marrow. Formation of osteoclast-like cells was increased in bone marrow cultures from rats with AIA, especially when bone marrow cells were cultured in the presence of marrow supernatant. Formation of resorption lacunae on ivory slices was increased in the marrow cultures from rats with AIA, especially from the right (adjuvant inoculated) tibia. AIA rat marrow supernatant promoted osteoclast-like cell formation in control culture, and this was significantly suppressed by an anti-IL-1 antibody. Rats with AIA showed a significant decrease in the bone mineral density of the periarticular regions of the tibia and femur. CONCLUSION: An uncoupled state in bone resorption-formation linkage, possibly mediated through an increase of IL-1 in the bone marrow, may contribute to the development of periarticular osteopenia in inflammatory arthritis.
Animals↗
Clinical characteristics of synchronous multiple lung cancer associated with idiopathic pulmonary fibrosis. A review of Japanese cases.
To define the clinical characteristics of multiple lung cancer (LC) associated with idiopathic pulmonary fibrosis (IPF), we reviewed 154 LC patients associated with IPF: 23 patients with synchronous multiple LC (IPF-multiple LC group) and 131 with single LC (IPF-single LC group), and these were compared with 4,931 patients with LC from 1975 to 1977 in Japan (whole LC group). In the IPF-single and IPF-multiple LC groups, most tumors were observed in male patients (91% and 96%), smokers (94% and 100%), and in peripheral regions of the lung (91% and 98%). The incidence of occurrence in the lower lobes, where a fibrotic shadow was prominent, was significantly higher in the IPF-LC groups (58% and 67%) than for the whole LC group (37%). The distribution of histologic types in the IPF-single LC group was similar to that of the whole LC group. However, the incidence of small cell carcinoma was significantly higher in the IPF-multiple LC group (33%) than for the IPF-single LC (14%) and whole LC (12%) groups. These results indicate that the features characteristic to synchronous multiple LC in patients with IPF are as follows: (1) male patients; (2) smokers; (3) small cell carcinoma histologic type; (4) lower lobes; and (5) peripheral type, all of which show a high rate of occurrence.
Aged↗
Relationship of haptoglobin polymorphism to malaria in the Solomon Islands.
Haptoglobin (Hp) polymorphism and its relationship to malaria infections was examined in Solomon Islanders under 25 years of age. The slide positive rate for malaria was 48% (53/111): Plasmodium vivax (Pv) 21 cases, Plasmodium falciparum (Pf) 16 cases and the remaining 16 were a mixture of Pv/Pf/P. malariae. Of 111 subjects examined, 17% (19 subjects) were ahaptoglobinemic (HpO). No association was observed between HpO and parasitemia, gender, anemia, serum insulin-like growth factor-1 (IGF-1) level, blood glucose level and enlargement of the spleen. These results suggest that malaria may not be the major cause of HpO in the people of the Solomon Islands.
Adolescent↗
[Drug induced obesity].
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Adrenal Cortex Hormones↗
[A case of slowly progressing interstitial pneumonia associated with idiopathic thrombocytopenic purpura].
A 72-year-old man had been taking 10 mg/day of prednisone since idiopathic thrombocytopenic purpura (ITP) was diagnosed when he was 60 years old. An interstitial lung shadow was observed on chest X-ray films when he was about 62 years old, and interstitial pneumonia (IP) (chronic-type), etiology unknown was diagnosed. With the progression of honey-comb shadows on the dorsal side of the lower lung fields, cystic changes on the anterior side of the upper lung fields also became more obvious. Slowly progressing IP associated with ITP is very rare. In addition, the chest CT findings of cystic changes on the dorsal side in the lower lung fields and on the anterior side in the upper lung fields are quite interesting.
Aged↗
Increased serum lipoprotein(a) levels in systemic lupus erythematosus with myocardial and cerebral infarctions.
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Adult↗
[A case of rheumatoid arthritis with a remarkable left-right difference in pulmonary lesions and acute exacerbation of pneumonia].
A 59-year-old woman had a four-year history of rheumatoid arthritis. Despite treatment with prednisolone for interstitial pneumonia, her chest X-ray films revealed gradual progression of reticular shadows, mainly in the left lung, and during the third hospitalization she died of respiratory failure due to acute exacerbation of pneumonia. At autopsy, there was a remarkable difference in lung weight: left 250 g, right 510 g. Microscopically, the pulmonary lesion was mild fibrosing interstitial pneumonia, with remarkable luminal organization and macrophages in parts. The features of unilateral interstitial pneumonia with bronchiolitis obliterans organizing pneumonia were clearer in the left lung. The cause of the acute exacerbation and of the difference in interstitial pneumonia between sides could not be identified.
Arthritis, Rheumatoid↗
Attitudes to death and dying in the UK, New Zealand, and Japan.
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Attitude to Death↗
[Modification of vancomycin nephrotoxicity by other antibiotics in rats].
Vancomycin (VCM) was intravenously administered to rats for 14 days at doses of 150 mg/kg/day and 250 mg/kg/day alone or in combination with 1,000 mg/kg/day of latamoxef (LMOX), flomoxef (FMOX) or cefpirome (CPR) or 250 mg/kg/day of fosfomycin (FOM), and the influences of combined antibiotics on the VCM-induced renal damage were studied. The renal impairment caused by VCM alone was, morphologically, demonstrated mainly as regeneration of tubular epithelium: slight regeneration was observed in a half of rats administered 150 mg/kg/day and slight to extensive regeneration in all the rats administered 250 mg/kg/day. Clinical examinations found apparent increases in urinary LDH and MDH activities in rats administered 250 mg/kg/day, thus showing a good correlation with renal pathological changes. In addition, increase in kidney weight and increase in urinary NAG activity were noted, while changes in plasma urea-N and creatinine were mild, and gamma-GTP activity and protein in urine could not be used as a parameter of the renal impairment. The slight renal impairment as noted in rats administered VCM 150 mg/kg/day alone was not observed at all when LMOX or FMOX was administered concomitantly, and less pronounced even when FOM was administered concomitantly. When CPR was administered concomitantly, the changes were the same as those observed with VCM alone. The renal impairment in rats administered VCM 250 mg/kg/day was apparently less severe when combined with LMOX, FMOX and FOM than that in rats administered VCM alone, and this was supported by apparent reduction of clinical examination values as the parameter of VCM-induced nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[A case of eosinophilic pneumonia presenting as hemoptysis, with epithelioid cell granuloma on lung biopsy].
A 60-year-old woman was admitted because of hemoptysis and dyspnea on exertion, which began one month before admission and gradually increased. Chest X-ray film taken on admission showed an infiltrative shadow in and around the left posterior basal segment. Chest CT disclosed peripheral and patchy consolidation with some air bronchograms and interstitial thickening in the left basal segments. Bronchoalveolar lavage fluid contained many red blood cells and abnormally high numbers of eosinophils and lymphocytes. The specimen obtained by CT-guided lung biopsy revealed epithelioid cell granulomas, hemosiderin-laden macrophages, diffuse infiltration of small round cells with a few eosinophils and monocytes in the alveolar septa, and many eosinophils in the intraalveolar exudates. No pathogens of pulmonary eosinophilia were identified and there was no secondary pulmonary eosinophilia. Therefore, we diagnosed eosinophilic pneumonia with no obvious cause. Hemoptysis may have been due to alveolar hemorrhage of eosinophilic pneumonia. The hemoptysis and chest infiltrative shadow disappeared rapidly after the start of treatment with oral prednisolone.
Biopsy↗
Anti-human immunodeficiency virus type 1 activity of phosphorothioate analogs of oligodeoxynucleotides: penetration and localization of oligodeoxynucleotides in HIV-1-infected MOLT-4 cells.
Phosphorothioate antisense oligodeoxynucleotide against HIV-1 rev (S-ODN-rev) inhibits virus-induced cytopathic effects (CPE) in acute infection and inhibits the expression of HIV-1 core protein, p24, in chronically infected cells in vitro. HIV-1 reverse transcriptase activity was not affected by S-ODN-rev at the high concentrations of 5-25 microM, which were 250-1250 times higher than the concentration required to achieve 100% HIV-1-induced CPE inhibition. [32P]-labeled S-ODN-rev was rapidly uptaken by MOLT-4 cells, whereas [32P]-SO-ODN-rev and [32P]-O-ODN-rev were not. In the observation of FITC-S-ODN-rev-treated MOLT-4 cells by a confocal laser scanning microscope, diffuse fluorescence was apparently observed in the cytoplasm. Interestingly, fluorescence signals were accumulated in the nuclear region of chronically infected MOLT-4/HIV-1 cells 60 min after incubation. FITC-labeled homooligomer, FITC-S-dC20 and FIT-C-S-dT20, also accumulated in the nucleus of MOLT-4/HIV-1 cells, but weak fluorescence was observed on the cell membrane and in the cytoplasm of the FITC-S-random treated MOLT-4/HIV-1 and MOLT-4 cells.
Cell Line, Transformed↗