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Biomedical subjects

T Yoshio

Publications and source records attributed to T Yoshio.

At least 19 recordsLinked to original sources
PubMed2000

Nucleolin as the earliest target molecule of autoantibodies produced in MRL/lpr lupus-prone mice.

To elucidate the autoantigen against which autoantibodies are produced in the earliest phase of the disease process of systemic lupus erythematosus (SLE), serum samples were collected individually and serially from 10 NZB/NZW F1 and 10 MRL/lpr mice. Using immunoblots with mouse thymoma cell (EL-4) lysates as substrates, all mice were found to generate autoantibody against an either 150-kDa, 110-kDa, 75-kDa, or 55-kDa molecule in as early as 4 weeks. Anti-DNA antibodies occurred almost at the same time or after those against these four molecules. The number of antigens reactive with autoantibodies in immunoblots increased gradually with age. Antibodies against histone molecules were produced after 8 weeks of age. Among the four antigens, the 110-kDa molecule was identified as nucleolin, which is an abundant nucleolar phosphoprotein. Nucleolin binds DNA, RNA, and nucleic acid-binding proteins such as histone H1. Nucleolin is a target of granzyme A of cytotoxic T cells, and autoantibodies against it are found in sera from patients with SLE as well as from those with various viral infections. These results indicate that nucleolin is one of the immunodominant molecules that break down self-tolerance and initiate autoantibody-spreading in a mouse model of SLE.

Aging↗
PubMed2000

Subarachnoid hemorrhage and systemic lupus erythematosus.

The frequency, clinical profile, treatment and outcome of subarachnoid hemorrhage (SAH) in patients with systemic lupus erythematosus (SLE) were assessed retrospectively, based on the case records of SLE of the Jichi Medical School Hospital over a 20 year period. Clinically defined SAH was found in 10 (3.9%) out of 258 SLE patients, which represented a frequency higher than previously assumed. Five patients had active SLE and lacked an apparent cause of SAH, other than SLE. A high mortality rate (5/5), no visible aneurysm on angiogram (3/4), and an onset during intractable SLE or after discontinued or no steroid therapy because of medical noncompliance (4/5) were characteristic of patients with active SLE, and thus an earlier successful suppression of SLE, if possible, might have prevented their SAH. In contrast, in the 5 patients with inactive SLE, 2 out of 3 saccular aneurysms were successfully clipped and small bleeding of one patient without aneurysms remitted spontaneously without the need for additional steroid therapy. When one death, which occurred outside of medical care, was excluded, the survival ratio of the hospitalized SAH patients with inactive SLE was significantly better than that with active SLE (3/4 versus 0/5, P=0.0476). In conclusion, the relatively common occurrence of SAH in SLE patients, and a significantly different clinical impact of SAH in respect to active and inactive SLE, were suggested from the results.

Adult↗
PubMed2000

[Three patients with systemic sclerosis complicated by microangiopathic hemolytic anemia and thrombocytopenia].

Clinical profiles and the treatment process of three female patients with systemic sclerosis (cases 1, 2, and 3) complicated by thrombotic microangiopathic hemolytic anemia (TMHA) were described. Thrombocytopenia preceded renal damage and hypertension in cases 1 and 2, although the chronological relationship between these parameters were unknown in case 3. Plasma exchange therapy using fresh frozen plasma was beneficial in cases 1 and 2. Cases land 3 presented with delirium and fluctuating psychosis, respectively. Early detection of thrombocytopenia and insidious hemolysis might be essential for starting effective plasmapheresis treatment in a part of patients with scleroderma kidney who present with thrombotic thrombocytopenic purpura (TTP) like disorder.

Aged↗
PubMed2000

In vitro and in vivo inhibition of activation induced T cell apoptosis by bucillamine.

OBJECTIVE: To investigate the mechanism of autoimmune phenomena, occasionally seen in patients with rheumatoid arthritis treated with bucillamine (BUC) and D-penicillamine (D-Pen), by evaluating their effects on apoptosis of T cells induced by T cell receptor activation or dexamethasone. METHODS: In vitro apoptosis was induced in a T cell hybridoma (SSP3.7) and a B cell line (WEHI 231) by activation of respective receptors or dexamethasone, in the presence or absence of BUC or D-Pen. In vivo apoptosis was induced in BALB/c mice by staphylococcal enterotoxin B (SEB), with or without BUC or D-Pen, and thymocytes were examined for it by FACS. RESULTS: Stimulation with anti-CD3 and dexamethasone induced apoptosis in 72% and 71% of SSP3.7 cells, respectively. However, only 16% of SSP3.7 cells became apoptotic by anti-CD3 when BUC was added to the culture media. By contrast, 80% of SSP3.7 cells became apoptotic when stimulated by dexamethasone, even in the presence of BUC. BUC did not affect apoptosis of WEHI 231 cells induced by anti-IgM. Although SA981 (a metabolite of BUC) inhibited apoptosis of SSP3.7 cells induced by anti-CD3, D-Pen did not. BUC, SA981, or D-Pen did not significantly influence the level of interleukin 2 secretion stimulated by anti-CD3. In contrast, both BUC and D-Pen inhibited apoptosis of Vbeta8+ thymocytes induced in vivo by SEB superantigen. Neither BUC nor D-Pen significantly changed the number of CD4+CD8+ thymocytes in BALB/c mice injected with dexamethasone. CONCLUSION: BUC decreased, while D-Pen did not, the apoptosis of T cells stimulated by anti-CD3 in vitro, although they both inhibited the deletion of immature thymocytes reactive with SEB in vivo. This may explain autoimmune phenomena sometimes seen during the treatment of rheumatic patients with these drugs.

Animals↗
PubMed2000

[Rapidly progressed secondary amyloidosis in a patient with Still's disease with gamma-allele in his SAA 1 gene].

A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non-steroidal anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastro-intestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of beta- and gamma-allele. The presence of gamma-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.

Adolescent↗
PubMed1999

Characterization of the 4C8 antigen involved in transendothelial migration of CD26(hi) T cells after tight adhesion to human umbilical vein endothelial cell monolayers.

In extravasation of T cells, little is known about the mechanisms of transendothelial migration subsequent to the T cells' tight adhesion to endothelium. To investigate these mechanisms, we developed a monoclonal antibody (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture system in which high CD26-expressing (CD26(hi)) T cells preferentially migrate through human umbilical vein endothelial cell (HUVEC) monolayers cultured on collagen gels. Anti-4C8 reacted with all CD3(+) T cells and monocytes but not neutrophils or HUVECs. The structure defined by this antibody was an 80-kD molecule. The mAb at 1 mug/ml inhibited 80-90% of migration of CD3(+) T cells through unstimulated and interferon gamma-stimulated HUVEC monolayers without interfering with adhesion and cell motility. When added to the cultures after the adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T cells. Phase-contrast and electron microscopy revealed that T cells are arrested at the intercellular junctions of HUVECs in the presence of anti-4C8. Anti-4C8 exhibited agonistic effects on resting T cells without other stimuli under culture conditions in which anti-4C8 can stimulate T cells. First, in the checkerboard assay using collagen gels, the antibody promoted chemokinetic migration of the cells in a dose-dependent manner from 0.1 to 10 mug/ml. The predominant population of T cells that migrated into collagen gels with impregnated anti-4C8 were CD26(hi). Second, solid-phase-immobilized anti-4C8 induced adhesion of T cells to the substrate, often with polarizations in cell shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti-4C8 augmented F-actin content preferentially in CD26(hi) T cells when added to T cells at a high dose of 10 mug/ml. Finally, both anti-4C8-induced chemokinetic migration and transendothelial migration were inhibited by pretreatment of T cells with pertussis toxin. These findings suggest that stimulation via the 4C8 antigen increases cell motility of CD26(hi) cells with profound cytoskeletal changes through signaling pathways including G proteins. The 4C8 antigen may be involved in preferential transmigration of CD26(hi) cells adherent to HUVECs.

Actins↗
PubMed1999

Localized scleroderma associated with progressing ischemic stroke.

We present a 73 year-old Japanese woman with localized scleroderma involving the right side of the scalp accompanied by continuous tingling pain, who developed insidiously progressive left hemiparesis. In magnetic resonance imaging of the brain, an infarct first appeared in the watershed region of the right middle cerebral artery territory and subsequently extended to deep white matter accompanied by scattered hemorrhages. Focal stenosis in the M2 portion of the right middle cerebral artery was revealed on magnetic resonance angiography, and the distal vessels were only shown faintly. A biopsy specimen from the sclerotic scalp lesion showed obvious thickening of vessel walls and mild mononuclear cell infiltration. We believe that the progressing ischemic stroke was caused by hemodynamic disturbances from localized sclerotic obstruction of the middle cerebral artery, with an autoimmune pathogenesis.

Aged↗
PubMed1999

Circulating myeloperoxidase and anti-myeloperoxidase antibody in patients with vasculitis.

To evaluate a role of myeloperoxidase (MPO) and antibody to myeloperoxidase (anti-MPO) in vasculitis, MPO and anti-MPO were determined by enzyme-linked immunosorbent assays in sera from 43 patients with vasculitis, 40 with rheumatoid arthritis, 36 with systemic lupus erythematosus (SLE), 23 with mixed connective tissue disease, 13 with systemic sclerosis, 22 with polymyositis/dermatomyositis, 18 with Sjögren's syndrome, and 30 normal controls. Kidney and lung sections from patients with vasculitis were stained for MPO. Anti-MPO titers were significantly higher (p<0.005) in the patients with vasculitis (mean+/- SD absorbance at 405 nm: 0.53 +/- 0.37) than in any other groups (0.15 +/- 0.04 to approximately 0.21 +/- 0.11). MPO levels in patients with vasculitis were comparable with those in patients with other diseases except SLE. In two patients with vasculitis, anti-MPO decreased sharply with simultaneous increases in MPO 1-2 weeks after they developed pulmonary hemorrhage. Numerous cells positive for MPO infiltrated the Bowman's spaces. These results indicate that MPO may contribute to the pathogenesis of vasculitis and a sudden fall in anti-MPO may predict a poor prognosis in some cases.

Animals↗
PubMed1998

Acute acalculous cholecystitis in systemic lupus erythematosus: a case report and review of the literature.

A 27-year-old woman with systemic lupus erythematosus (SLE) was found to have acute acalculous cholecystitis. At the time of admission, the patient was not under corticosteroid or immunosuppressive therapy. Computed tomography (CT) and ultrasonography revealed findings in the gall bladder consistent with acute acalculous cholecystitis. Her abdominal pain completely disappeared following corticosteroid therapy, with dramatic improvement in the images of CT and ultrasonography. Six similar cases of SLE complicated with acute acalculous cholecystitis have been reported in the literature and they were all treated surgically by cholecystectomy or cholecystostomy. This is the first case report in which acute acalculous cholecystitis accompanying SLE was treated successfully by corticosteroid without surgical intervention.

Acute Disease↗
PubMed1998

A close temporal relationship of liver disease to antiribosomal P0 protein antibodies and central nervous system disease in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether there is a close temporal relationship of liver disease to serum IgG and/or IgM antiribosomal P0 protein antibodies (anti-P0) and central nervous system (CNS) lupus in patients with systemic lupus erythematosus (SLE). METHODS: The study included 70 patients with active SLE. Of these, 30 had IgG and/or IgM anti-P0 and 14 had CNS lupus other than psychiatric disease (nonpsychiatric CNS lupus). Of these 14 patients, 11 had anti-P0. Laboratory manifestations of liver disease were retrospectively analyzed. RESULTS: Liver disease not attributed to any cause other than SLE (SLE liver disease) was present in 8 of the 11 patients with anti-P0 with nonpsychiatric CNS lupus (72.7%), in none of the 19 patients with anti-P0 without nonpsychiatric CNS lupus (0%), and in one of the 40 patients without anti-P0 (2.5%). The prevalence of SLE liver disease was significantly greater in patients with anti-P0 with nonpsychiatric CNS lupus than in the other 2 groups (p < 0.0001). Mean levels of liver enzymes (lactate dehydrogenase, glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, gammaglutamyl transpeptidase) were significantly higher in patients with anti-P0 with nonpsychiatric CNS lupus than in the other 2 groups. Serial studies in 3 patients showed that the appearance of anti-P0 and liver dysfunction slightly preceded the onset of nonpsychiatric CNS lupus. CONCLUSION: Anti-P0 may be related to the pathogenesis of CNS lupus and SLE liver disease found simultaneously in SLE. The appearance of anti-P0 and liver dysfunction may predict onset of CNS lupus.

Adolescent↗
PubMed1997

Preferential binding with Escherichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoid arthritis.

One hundred thirty-two patients with various connective tissue disorders, including 60 with rheumatoid arthritis (RA), had antibodies against human as well as Escherichia coli hsp60 in titers significantly higher than those of normal controls. There was a correlation between titers of antibody to human hsp60 and those to E. coli hsp60. Levels of antibodies against human and E. coli hsp60 were lower in joint fluids than in sera, indicating little production of antibodies in the joint. Antibodies affinity-purified with E. coli hsp60 bound strongly with the homologous hsp60, but weakly with human hsp60. However, antibodies affinity-purified with human hsp60 bound comparably with both E. coli hsp60 and human hsp60. Antibodies affinity-purified with Mycobacterium tuberculosis hsp65 bound to human hsp60 with a reactivity similar to the reactivity of those affinity-purified with human hsp60. The reactivity to the three hsp60 species was lost when sera were absorbed with E. coli hsp60, while the reactivity to E. coli hsp60 remained after extensive absorption with M. tuberculosis hsp65 or human hsp60. These results indicate that anti-hsp60 antibodies in patients with RA and other connective tissue disorders are raised by infection with intestinal microorganisms such as E. coli. They may represent another example of autoimmune responses triggered by antigenic mimicry of host proteins to microbes and suggest that the reactivity of antibodies from RA patients with M. tuberculosis hsp65 might have been a cross-reaction with the E. coli homologue.

Antibodies↗
PubMed1997

Undectable expression of hMLH1 protein in sporadic colorectal cancer with replication error phenotype.

PURPOSE: Four DNA mismatch repair genes have been identified as being susceptible genes for hereditary nonpolyposis colorectal cancer. Deficiency of one of the mismatch repair genes causes the replication error phenotype in more than 80 percent of patients with hereditary nonpolyposis colorectal cancer and in 10 to 30 percent of patients with sporadic colorectal cancer. To determine which mismatch repair gene is lacking the function in patients with replication error-positive colorectal cancer, several approaches have been used at the nucleic acid and protein levels. We studied replication error in 40 samples of randomly selected colorectal cancers and expression of hMSH2 and hMLH1 proteins analyzed by immunoblot in the tumor and normal tissues of the replication error-positive and replication error-negative samples. MATERIALS AND METHODS: Frozen tumor and normal tissues were obtained from 40 Japanese patients who had colorectal cancer. According to the Amsterdam criteria, those patients were classified as having 39 sporadic and 1 unknown colorectal cancers. Genomic DNA was extracted from tumor and normal tissues for determining replication error with eight microsatellite markers. Expression of hMSH2 and hMLH1 proteins in cell lysates of tumor and normal tissues of 16 patients was analyzed by immunoblot. RESULTS: The replication error phenotype was found in 6 (15 percent) of the 39 sporadic cases. hMLH1 protein was not detected in two of the six replication error-positive tumor tissues and not in the normal tissues, indicating that the tumor cells of the two patients had severe mutations in both alleles of the hMLH1 gene. Another four replication error-positive and ten replication error-negative tumors and normal tissues expressed hMLH1 protein. hMSH2 protein was detected in all samples. CONCLUSION: hMLH1 protein was undetectable in the two tumor tissues of the six replication error-positive samples of sporadic colorectal cancer. The detection procedure used here may have potential use for determining a dysfunctional mismatch repair gene product.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Association of interleukin 6 release from endothelial cells and pulmonary hypertension in SLE.

OBJECTIVE: To investigate how sera from 37 patients with systemic lupus erythematosus (SLE) stimulate interleukin (IL) 6 release from IL-1beta pretreated endothelial cells and compare these effects to those of sera from 16 normal controls. METHODS: Endothelial cells pretreated 18 h with IL-1beta (5 U/ml) were incubated 2 h with sera diluted 10-fold with phosphate buffered saline (PBS). IL-6 concentrations in endothelial culture supernatants collected after incubation were measured by ELISA. RESULTS: Compared with PBS, sera from controls and 24 patients with SLE suppressed IL-6 release from IL-1beta pretreated cells. However, sera from 13 patients with SLE augmented IL-6 release. Of note, sera from 5 patients with pulmonary hypertension induced the highest level of IL-6 release. IgG from control sera suppressed IL-6 release, whereas F(ab')2 did not. Both IgG and F(ab')2 from the sera of patients with SLE with pulmonary hypertension augmented IL-6 release from IL-1beta pretreated cells. CONCLUSION: IgG antiendothelial cell antibodies from patients with SLE may be associated with the pathogenesis of SLE and pulmonary hypertension.

Adolescent↗
PubMed1997

Detection of large macrophage colony forming cells in the peripheral blood of patients with rheumatoid arthritis.

OBJECTIVE: To test for the presence of colony forming cells, that form large macrophage colonies (> 2.5 mm in diameter, > 10,000 cells), in the peripheral blood of patients with rheumatoid arthritis (RA) and to determine its association with the clinical and laboratory features of RA. METHODS: Peripheral blood mononuclear cells (PBMC) from 96 patients with RA and 20 healthy controls were assayed for in vitro colony formation. In addition, PBMC from 38 patients with other rheumatic diseases including systemic lupus erythematosus (SLE), progressive systemic sclerosis (SSc), and polymyositis/dermatomyositis (PM/DM); 23 patients with infectious inflammatory diseases were also assayed. RESULTS: Large macrophage colony forming cells were detected in the peripheral blood of 19% of patients with RA (18/96), but not in that of healthy controls. In addition, these cells were detected in the peripheral blood of 11 of the 38 patients with other rheumatic disease (7/13 SSc and 4/11 PM/DM), but not in the 23 patients with infectious diseases. In the patients with RA, interstitial lung disease was significantly more frequently observed among patients in whom colony forming cells were found than among those in whom they were not found (p < 0.001). CONCLUSION: Based on the size of the colonies they formed, the macrophage colony forming cells detected in patients with RA probably corresponded to primitive hematopoietic progenitor cells, defined as high proliferative potential colony forming cells (HPP-CFC). Our observations provide preliminary evidence of the appearance of HPP-CFC in the circulation during inflammation of RA, and during that in other rheumatic diseases such as SSc and PM/DM, and of the association of HPP-CFC with interstitial lung disease in patients with RA.

Adult↗