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T Shimbo

Publications and source records attributed to T Shimbo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial aneurysms and myocardial infarction in young children. Prominent thrombocytosis with increased megakaryocytes develops during the convalescent period. To clarify the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (TPO) and other thrombopoietic cytokines in 40 patients with KD (149 samples) and 106 age-matched controls using ELISA. TPO values in the controls were 1.94 +/- 0.69 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85 to 3.27 fmol/ml. In the first week of KD, platelet counts were normal but TPO values increased (approximately 15.5 fmol/ml). TPO levels peaked on day 6 +/- 2 at 5.94 +/- 2.64 fmol/ml and then fell gradually. When platelet counts peaked in the second to third weeks, TPO levels were still high or comparable with the controls. TPO levels in KD patients with normal platelet counts were significantly higher than control levels. Interleukin (IL)-6 levels in the first week rose, but neither IL-11 nor leukemia inhibitory factor was detectable. These results suggest that TPO contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production may be enhanced during the acute phase.

Child↗
PubMed1997

Effects and serum levels of thrombopoietin in a case of chronic thrombocytopenia with achondroplasia.

Thrombopoietin (TPO), produced mainly in the liver, is a major regulator of platelet production. Serum TPO levels are generally increased in thrombocytopenia. We report a case of a 12-year-old boy with chronic severe thrombocytopenia, achondroplasia and nephritis. Severe chronic thrombocytopenia was found at 9 months of age. It was resistant to any treatment. Studies on megakaryocytic colonies in vitro revealed that the marrow cells responded well to TPO and no plasma inhibitor was found. Although hepatic function test results were normal, serum TPO levels in the patient (0.94 fmol/ml) were consistent with those in age-matched children (0.49-1.75 fmol/ml). Chronic thrombocytopenia requires individual evaluation before clinical trials with TPO.

Achondroplasia↗
PubMed1997

The production of IL-8 in cerebrospinal fluid in aseptic meningitis of children.

Neutrophils accumulate initially in the cerebrospinal fluid (CSF) of aseptic meningitis, perhaps because of increased levels of granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein-1alpha (MIP-1alpha), and IL-8 in the subarachnoid space. We studied levels of these cytokines in children with aseptic meningitis using ELISA. When meningeal symptoms existed, IL-8 levels (1399 +/- 1600 ng/l, n = 32) in the CSF were significantly higher than those either after meningeal symptoms disappeared (61 +/- 56 ng/l, n = 18) or in controls (44 +/- 63 ng/l, n = 27) (P < 0.0001). High levels of IL-8 on admission dropped sequentially. Significant correlations were found between IL-8 levels and either neutrophil counts (r = 0.612), G-CSF levels (r = 0.873) or MIP-1alpha levels (r = 0.623) in the CSF of the affected patients (P < 0.0001). IL-8 values in serum were lower than in the corresponding CSF samples from all individuals with meningeal symptoms. The IL-8 mRNA was detectable by reverse-transcribed polymerase chain reaction (PCR)-assisted amplification in fresh leucocytes from the CSF, but not from the peripheral blood of a healthy volunteer. The culture of CSF mononuclear cells produced high levels of IL-8 (approximately 2750 ng/l). These data indicate that IL-8 levels rise transiently at the initial stage of aseptic meningitis, and that mononuclear cells that migrate into the CSF are a cellular source of this chemokine. We suppose that IL-8, in addition to G-CSF and MIP-1alpha, contribute to the localized neutrophil accumulation during the disease.

Adolescent↗
PubMed1997

The production of macrophage inflammatory protein-1alpha in the cerebrospinal fluid at the initial stage of meningitis in children.

Neutrophils in the cerebrospinal fluid (CSF) increase during the initial stage of meningitis. Some cytokines induce the accumulation of such neutrophils, and we and other investigators have revealed transient increases in the levels of granulocyte-colony stimulating factor (G-csf) and IL-8 in the CSF of patients with meningitis. To explore the coordination of other cytokines with G-csf and IL-8 in the neutrophil accumulation in the CSF, we herein investigated macrophage inflammatory protein-1alpha (MIP-1alpha), which can induce the infiltration of neutrophils. The modulation of MIP-1alpha levels in the CSF in children with bacterial (n = 10) and aseptic (n = 22) meningitis was examined using an ELISA. MIP-1alpha levels in the CSF were detectable at the stage with symptoms of meningitis: 289.9 +/- 270.7 ng/L in the bacterial meningitis group and 16.1 +/- 12.5 ng/L in the aseptic meningitis group. These levels decreased with the improvement of symptoms. MIP-1alpha was not detectable (<6 ng/L) in all of the control patients without meningitis (n = 19). The MIP-1alpha levels in the CSF showed a significant correlation with the CSF neutrophil counts (r = 0.750, p < 0.0001; n = 80) of meningitis, and the values of MIP-1alpha (log ng/L)/neutrophil counts (log/L) ratio were calculated (1.003 +/- 0.576). The MIP-1alpha levels in the serum were significantly lower than those in the CSF (p = 0.0464). We found MIP-1alpha mRNA in the CSF cells by the reverse transcriptase-PCR method, and high levels of MIP-1alpha protein in the culture media from mononuclear cells in the CSF in vitro. In summary, The MIP-1alpha level increases in the CSF at the symptomatic stage of meningitis in children, and its cellular source is, in part, mononuclear cells which have infiltrated the CSF. We propose that MIP-1alpha, in addition to G-csf and IL-8, plays an important role in the accumulation of neutrophils in the CSF of patients with meningitis.

Adolescent↗
PubMed1997

[Serum levels and in vitro production of IL-5 in children with bronchial asthma].

IL-5 play important roles in inflammatory responses in bronchial asthma, but little is known about serum levels and in vitro production of IL-5 in childhood bronchial asthma. We further examined serum IL-5 levels in children with bronchial asthma and the controls. IL-5 in serum was detected in all of asthmatic and disease-free individuals. Its values during asthma exacerbation were significantly higher than during remission of asthma. Serum IL-5 values did not significantly differ among groups divided by asthma severity. We studied IL-5 production by peripheral blood mononuclear cells cultured with or without Dermatophagoides farinae (Df) in children with mite allergy. IL-5 concentrations in culture supernatant from after stimulation with Df were significantly higher than those from asthmatic patients without stimulation and from the control subjects. In contrast, IL-5 levels in culture media from the controls were not significantly different between with and without stimulation with Df. Our results suggest that IL-5 may play roles in the pathogenesis of bronchial asthma.

Asthma↗
PubMed1996

Measurement of endogenous plasma granulocyte colony-stimulating factor in patients with acquired aplastic anemia by a sensitive chemiluminescent immunoassay.

Endogenous plasma granulocyte colony-stimulating factor (G-CSF) concentrations were serially measured in 68 patients with acquired aplastic anemia (AA). A very sensitive chemiluminescent immunoassay (CLEIA) was used to measure the plasma G-CSF concentration. The minimum detection limit of this assay (0.5 pg/mL) was sufficient for the determination of G-CSF concentrations in patients and normal subjects. The plasma G-CSF concentrations were significantly higher in 51 AA patients without signs of infection as compared with healthy control subjects. In AA patients with signs of infection, the G-CSF concentrations appeared to increase during the acute phase. There was a significant negative correlation between plasma G-CSF concentrations and absolute neutrophil counts (ANC) in AA patients without signs of infection. Although a decrease in the plasma G-CSF concentration was observed in all patients who achieved self-sustaining hematopoiesis following bone marrow transplantation (BMT) or immunosuppressive (IS) therapy, it was lower in patients undergoing BMT as compared with those receiving IS therapy for any given degree of neutropenia. Plasma G-CSF concentrations were higher in patients responding to IS therapy than in nonresponders. This study demonstrated the negative feedback regulation of G-CSF that plasma G-CSF concentrations may be useful in predicting the clinical response to IS therapy.

Adolescent↗
PubMed1996

Reference intervals for serum granulocyte colony-stimulating factor levels in children.

OBJECTIVE: To determine age-adjusted reference intervals for children for serum granulocyte colony-stimulating factor (G-CSF) levels. DESIGN: We determined the serum G-CSF levels of 168 disease-free children who were term neonates to 15 years of age with a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: The lowest values (5 ng/L) exceeded the detectable limit (1 ng/L) of this assay technique. The G-CSF levels were highest on the day of birth (mean +/- SD 147 +/- 146 ng/L); thereafter values decreased to 46 +/- 33 ng/L in the early neonatal period and to 23 +/- 10 ng/L in the late neonatal period. The G-CSF levels both on the day of birth and in the early neonatal period were significantly higher than in all older age groups. No significant differences were found among any of the age groups after 4 weeks of age. The G-CSF values were correlated with both blood leukocyte counts (r = 0.496, p < 0.0001) and neutrophil counts (r = 0.547, p < 0.0001). In children older than 4 weeks of age (n = 128), the 95% reference interval for G-CSF values was 5 to 42 ng/L. CONCLUSIONS: Our study in disease-free children revealed that change in serum G-CSF levels are age dependent and are correlated with neutrophil counts. Determination of reference intervals for the neonatal period requires further study.

Adolescent↗
PubMed1996

Production of interleukin-10 in the cerebrospinal fluid in aseptic meningitis of children.

IL-10 is a cytokine that has antiinflammatory properties. We investigated IL-10 using ELISA and a reverse-transcribed polymerase chain reaction in the cerebrospinal fluid (CSF) of children with or without aseptic meningitis. When the patients with aseptic meningitis had meningeal symptoms, IL-10 in the CSF was detectable in 14 of 22 patients (88 +/- 146 ng/L, n = 31). The IL-10 levels decreased as meningeal symptoms disappeared. In 20 of 21 control children without meningitis, CSF samples had no detectable levels of IL-10 (< 10 ng/L). Serum IL-10 levels were lower than the corresponding levels in the CSF from the same individuals with aseptic meningitis. Significant correlations were found between IL-10 levels and mononuclear cell counts in the CSF of the affected patients (r = 0.644, p < 0.001). The IL-10 mRNA was detected by reverse-transcribed polymerase chain reaction-assisted amplification in the CSF cells in four of seven patients with the disease. The culture of CSF mononuclear cells produced high levels of IL-10 (152-485 ng/L) in all of five patients. Cytokine kinetics in the CSF showed that mean IL-10 levels reached the peak on the 2nd to 3rd d of the illness, although all mean levels of IL-6, IL-8, and granulocyte colony-stimulating factor were the highest on the 1st d of the illness. In summary, IL-10 is produced in the CSF in aseptic meningitis, and may increase relatively late compared with the proinflammatory cytokines. IL-10 may play an immunoregulatory role in the meningeal inflammatory network.

Adolescent↗
PubMed1995

Expression of Id2 and Id3 mRNA in human lymphocytes.

Helix-loop-helix (HLH) transcription factors are involved in cellular growth and differentiation. The Id (inhibitor of DNA binding and differentiation) HLH proteins, in a dominantly negative fashion, regulate transcriptional activities of basic HLH proteins. We examined by northern hybridization the expression of Id2 and Id3 mRNA in human leukemia/lymphoma lines and patient samples, as well as resting and activated normal human lymphocytes from peripheral blood (PBL). The Id2 mRNA was abundantly expressed in 5/12 T-cell and 3/4 B-cell lines, and Id3 mRNA was detected in 4/12 T-cell and 3/4 B-cell lines. Interestingly, Id2, but not Id3, mRNA was strongly expressed in 4/5 T-cell lines infected with human T-cell leukemia virus type I (HTLV-I) (ATL-1k, MT-2, S-LB1) and type II (Mo). Another unexpected finding was that T-cell leukemias and T-cell lines often expressed either Id2 or Id3 mRNA. In addition, resting PBL constitutively expressed prominent levels of Id2 mRNA, but not Id3 mRNA. Upon PHA-stimulation, Id2 expression decreased and Id3 levels increased with biphasic kinetics. Taken together, our studies revealed three unexpected findings which require further analysis: (1) expression of Id2 mRNA is often associated with lymphocytic transformation by HTLV-I or -II; (2) T-cells usually express either Id2 or Id3 mRNA, but B-cells often express both simultaneously; (3) non-dividing, normal PBL express high levels of Id2 and no Id3 mRNA; and with the onset of cellular proliferation, levels of Id2 mRNA decrease while levels of Id3 mRNA increase, suggesting that regulation of expression of these closely related genes is disparate.

B-Lymphocytes↗
PubMed1995

Transient elevation of granulocyte colony-stimulating factor levels in cerebrospinal fluid at the initial stage of aseptic meningitis in children.

At the early stage of aseptic meningitis, there is a transient increase in neutrophil counts in the cerebrospinal fluid. Some factors in the cerebrospinal fluid might induce migration of neutrophils into the cerebrospinal fluid. Granulocyte colony-stimulating factor (G-CSF) plays an important role, not only as a hemopoietic factor but also as a regulating factor for a biologic defense system by neutrophils in the foci of infection. To analyze the role of G-CSF on accumulating neutrophils in the cerebrospinal fluid, we have measured G-CSF levels in the cerebrospinal fluid of children with aseptic meningitis, paying particular attention to the phasal transition. Within the first 2 d from the onset, G-CSF levels in the cerebrospinal fluid were 223 +/- 97 ng/L, significantly higher than those of the patients without meningitis (p < 0.01). Beyond the second day after the onset, the G-CSF levels rapidly decreased to below the detectable level, even though the patients manifested meningeal signs and symptoms. There was a direct relationship between G-CSF levels and neutrophil counts in the cerebrospinal fluid (r = 0.763, p < 0.01). During the first 2 d after the onset, the G-CSF level in the cerebrospinal fluid in each case was remarkably higher than that in the serum. This finding suggests that the G-CSF in the cerebrospinal fluid was produced in the spinal cavity. From our results, the transient elevation of G-CSF levels might lead to the transient increase in neutrophil counts in the cerebrospinal fluid by recruiting them from the peripheral blood at the initial stage of aseptic meningitis.

Adolescent↗
PubMed1994

Cost-effectiveness analysis of strategies for colorectal cancer screening in Japan.

To determine the cost-effectiveness of colorectal cancer screening strategies in Japan and to determine the influence of long-term compliance with screening programs on the selection of strategies, the natural history of a simulated cohort of 40-year-old Japanese of both genders was modeled with and without colorectal cancer screening until age 75 years. Survival, number of complications, and direct medical costs were compared among several combinations of screening examinations. In addition, the age of initiating screening was varied, as was the long-term compliance rate. Strategies using immunological fecal occult blood test were found to be the most cost-effective. Immunological fecal occult blood test followed by colonoscopy, if positive, would save 24.05 (5.88 discounted) days of life and cost 28,420 yen (US $210) per screened person, thus offering a cost-effectiveness ratio of 1.765 million yen (US $13,100) per year of life saved. If long-term compliance is 100%, initiating screening at age 40 years offers more years of life saved and a low incremental cost of screening. However, if more likely dropout rates are considered, initiation at age 40 years is dominated by later initiation of screening.

Adult↗
PubMed1993

Improvement of neutropenia and neutrophil dysfunction by granulocyte colony-stimulating factor in a patient with glycogen storage disease type Ib.

Patients with glycogen storage disease type Ib (GSD Ib) suffer from recurrent bacterial infections due to neutropenia and neutrophil dysfunction. To improve the quality of life in a 9-year-old boy with GSD Ib, we subcutaneously administered recombinant human granulocyte colony-stimulating factor (G-CSF). Daily injections of 100 micrograms/m2 of G-CSF significantly increased absolute neutrophil counts and augmented neutrophil mobility. The patient was then treated with 70 and 100 micrograms/m2 of G-CSF daily and twice-weekly. The treatment maintained absolute neutrophil counts at significantly higher levels than those without treatment for 22 months and markedly decreased the frequency of infections and the necessity for hospitalisation. Weekly injections of 70 micrograms/m2 of G-CSF were less efficient. No adverse effects were observed during treatment. These findings indicate that daily and twice-weekly treatment with G-CSF of long duration are safe and effective for patients with GSD Ib. G-CSF may be a useful therapeutic agent in patients with neutrophilic impairment as a consequence of a metabolic disorder.

Cell Movement↗
PubMed1992

[Elevated production of GM-CSF by peripheral blood mononuclear cells stimulated with mite antigens in children with bronchial asthma].

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine which can stimulate the proliferation and functions of eosinophils and neutrophils. We have studied whether peripheral blood mononuclear cells (PBMC), obtained from children with stable asthma, can produce GM-CSF through stimulation with crude Dermatophagoides farinae (Df) antigen in vitro. The patients had strongly positive RAST results for house dust mite Df. Levels of GM-CSF in PBMC culture supernatant were assayed by an enzyme immunoassay. When stimulated with Df antigen, patient's PBMC released significantly increased levels of GM-CSF compared with unstimulated ones. PBMC of non-allergic controls, however, did not. The addition of polymyxin B, an inactivator of endotoxin, did not suppress the Df-antigen-induced production of GM-CSF. Levels of GM-CSF produced by PBMC stimulated with Df antigens were significantly higher in the patients than in the controls. These results indicate that PBMC of children with Df-allergic asthma, unlike those of non-allergic children, can produce elevated levels of GM-CSF by stimulation with Df antigens.

Animals↗
PubMed1992

[Suppression of in vitro hemopoiesis by the monocytes in a patient with aplastic anemia associated with hepatitis].

The cause of aplastic anemia associated with hepatitis (AAH) is as yet still unknown. There is a supposed relation to the immune mechanisms, however few reports have shown the effects of monocytes on the pathogenesis in the patients with AAH. We have reported a case of a 12-year-old boy with AAH related to cytomegaloviruses, and studied the hemopoietic progenitors. He showed pancytopenia and hypoplasia of the bone marrow on admission to our hospital. The culture studies showed that mononuclear cells (MNC) of the bone marrow produced few hemopoietic colonies in all cell lineages. However, the depletion of adherent cells from the MNC increased numbers of erythroid, neutrophil-macrophage and megakaryocyte colonies. Furthermore, the addition of adherent cells of the peripheral blood suppressed the colony formation in the aforementioned cell lineages by marrow MNC from which adherent cells, phagocytic cells and T-cells were abrogated. The results way suggest that monocytes play some soles in the pathogenesis of aplasia through inhibitor of hemopoiesis.

Anemia, Aplastic↗
PubMed1991

Induction of granulocyte and granulocyte-macrophage colony-stimulating factors from human monocytes stimulated by Fc fragments of human IgG.

The effect of human IgG on human haemopoiesis has been studied in vitro. Dialysed purified IgG stimulated haemopoietic colony growth by bone marrow mononuclear cells (MNC) but not by monocyte-depleted MNC. Culture media, conditioned by IgG-stimulated peripheral blood MNC, augmented formation of neutrophil-macrophage, eosinophil, and megakaryocyte colonies by monocyte-depleted marrow MNC. Serum-free IgG-conditioned media also contained colony-stimulating activity (CSA). IgG Fc fragments and heat-aggregated IgG promoted the secretion of CSA, but F(ab')2 fragments, Fab fragments or ultracentrifuged IgG did not. In the cell-selection studies, CSA was produced by highly enriched monocytes following stimulation with Fc fragments. The antiserum against human granulocyte colony-stimulating factor (G-CSF) and/or granulocyte-macrophage CSF (GM-CSF) neutralized the CSA produced by Fc fragment-activated monocytes. Enzyme immunoassays showed G-CSF and GM-CSF in media conditioned by monocytes stimulated with the Fc fragments, heat-aggregated IgG and anti-D-sensitized red blood cells (RBC). Northern hybridization analysis showed mRNA encoding G-CSF and GM-CSF in RNA extracted from MNC and monocytes cultured with the Fc fragments, but not in the RNA from unstimulated cells or monocyte-depleted MNC. These results indicate that IgG Fc fragments, aggregated IgG and antigen-antibody complexes induce monocytes to produce G-CSF and GM-CSF in vitro. The CSFs release induced by IgG may be involved in the in vivo regulatory network in haemopoiesis.

Cell Division↗
PubMed1989

[Relapse of acute monocytic leukemia present with skin and tracheal involvement].

A 34 year-old female was admitted because of anemia and leukopenia. Her bone marrow contained abundant blastic cells, which were histochemically positive for peroxidase and alpha-naphthyl butyrate esterase, but negative for ASD chloroacetate esterase. She was diagnosed as acute monocytic leukemia (FAB, M5a). Complete remission was achieved after the administration of BHAC, daunorubicin, 6MP and prednisolone, and she was discharged after consolidation therapies. But shortly later, she noticed hoarseness and erythematous nodules on her breast and abdomen. Though the examinations of peripheral blood and bone marrow did not show any abnormality, hoarseness rapidly worsened and she complained of dyspnea. X-ray and CT scan demonstrated narrowing of the trachea under the cricoid cartilage, and trans-tracheal biopsy revealed leukemic involvement. In addition, erythematous skin lesion showed the infiltration of leukemic cells by biopsy. Although radiation and chemotherapy was initiated, she died of pneumonia. We tried to discuss the laryngo-tracheal and skin involvement of acute monocytic leukemia as early symptoms of relapse.

Adult↗
PubMed1989

[Spinal cord compression by primary epidural non-Hodgkin lymphoma].

A 63-year-old man was admitted because of sudden paraparesis. Myelography revealed a complete block at the level of T-3. The spinal epidural tumor was histologically diagnosed as malignant lymphoma, diffuse large cell type and immunohistochemically B-cell type. A thorough work-up for metastasis including MRI was negative. He was postoperatively treated with combination chemotherapies (VEPA), followed by irradiation to the region. The residual tumor disappeared on chest-CT and the patient's neurological status rapidly improved. He is still in remission for 18 months and has full performance status. This case is a very rare lymphoma originated from spinal-epidural space.

B-Lymphocytes↗