Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10-producing regulatory T cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3-primed CD11c(-) DCs activated T cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.

Cell Differentiation↗

PubMed2001

Alteration of peripheral blood dendritic cells in patients with primary Sjögren's syndrome.

OBJECTIVE: We recently identified 3 fractions of human peripheral blood (PB) dendritic cells (DC), including the monocyte-associated fractions 1 and 2 (CD1a+,CD11c+ and CD1a-,CD11c+, respectively) and the lymphoid-associated fraction 3 (CD1a-,CD11c-). We attempted to determine whether these fractions were altered in Sjögren's syndrome (SS). METHODS: We examined 23 patients with primary SS and 22 normal control subjects. DC were purified from PB and analyzed by flow cytometry. Immunohistochemical staining of labial salivary glands of SS patients was performed with monoclonal antibodies against fascin, which is known to be specific for DC. RESULTS: The total numbers of PB DC and fraction 1 DC were decreased in SS. Immunohistochemical staining demonstrated that fascin+,CD11c+,HLA-DR+ mononuclear cells were present and scattered among numerous fascin-hyperfiltrating cells in SS patients. Interferon-gamma (IFNgamma)-producing Th1 cells were shown to be increased in both PB and salivary glands of patients, indicating the presence of general IFNgamma-producing Th1 polarization in SS. Furthermore, numbers of Thl cells were increased when naive T cells were cocultured with fraction 1 DC in vitro. CONCLUSION: These findings suggest selective trafficking of fraction 1 DC into focal sites of inflammation and subsequent promotion of Th1 balance, suggesting a novel pathogenesis of SS.

Adult↗

PubMed2001

A Hodgkin's disease cell line, KM-H2, shows biphenotypic features of dendritic cells and B cells.

The origin of Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin's disease, has long remained controversial. Dendritic cells (DCs) are highly specialized antigen-presenting cells that have the unique capacity to prime naive T cells, and they may be progenitors of RS cells in a population of Hodgkin's disease cells. In this study, the KM-H2 cell line, previously established from a patient with Hodgkin's disease of mixed cellularity, was reevaluated for its cellular derivation, particularly in terms of DCs. KM-H2 cells were demonstrated to carry the newly proposed DC-associated molecules fascin, CD83, and DEC-205, as well as costimulatory molecules such as CD40, CD80, and CD86. In addition, KM-H2 cells were shown to be able to potently stimulate peripheral blood T cells and to have the strong endocytotic activity of fluorescein isothiocyanate-dextran. On the other hand, KM-H2 cells were shown to have variable-diversity-joining recombination of the immunoglobulin H gene, although they did not express any subclasses of immunoglobulin and they were negative for CD79a and CD79b. In addition, KM-H2 cells produced the messenger RNA of the Pax-5 gene. These findings lead to a hypothesis that KM-H2 cells originated from the cells that had differentiated through the possible common DC-B-cell progenitors along the newly proposed pathway.

Adult↗

PubMed2001

CD3+CD4-CD8-TCR-alphabeta+ T-cell lymphoma with clinical features of primary effusion lymphoma: an autopsy case.

We report an unusual case of T-cell lymphoma presenting as ascites. A 72-year-old HIV-negative woman was admitted to our hospital for abdominal discomfort associated with increasing abdominal girth over the course of 1 month. Physical examination showed a tense and distended abdomen and edema of the lower extremities. There was no hepatosplenomegaly or lymphadenopathy. A computed tomographic scan of the abdomen and chest showed massive ascites and pleural effusions, but there was no evidence of tumor masses or lymph node enlargement. The cytospin prepared from the peritoneal fluid was hypercellular and composed of a population of monotonous, large cells containing fine chromatin. No herpesvirus-8 (HHV-8) DNA was detected by polymerase chain reaction in the cells. Immunohistochemistry showed the neoplastic cells to be CD3+, CD4, CD7+. CD8-, CD34-, CD56, and TCR-alphabeta+. Repeated cytogenetic studies showed common abnormalities of del(1) (p11p22), +i(7)(ql0), and t(11:14)(q23;q11). The morphologic and immunologic findings were suggestive of peripheral T-cell lymphoma (PTCL), unspecified. This case suggests that some PTCLs with clonal chromosomal aberrations can exhibit peculiar serosal spreading in the absence of HHV-8 infection.

Aged↗

PubMed2001

High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells.

Interaction between leukocyte and endothelial cells (ECs) is essential for vascular homeostasis and competent immune-inflammatory responses in vivo. Platelet-derived microparticles (PMPs) are generated by high shear stress and may appear in diseased small arteries and arterioles in various clinical settings. In this study, we used flow cytometry and confocal laser scanning microscopy to investigate the effects of high-shear-induced platelet and microparticle activation in adhesion molecules of THP-1 and ECs. We also measured the production of some cytokines and studied cytokine mRNA from THP-1 and ECs after PMP stimulation. PMP stimulation of THP-1 cells increased CD11b, CD32, and CD33 but not CD29, CD31, and CD36. PMP stimulation of ECs increased CD54 and CD63 but not CD9, CD29, and CD31. PMPs induced interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) production by THP-1. PMPs also induced IL-8, IL-1 beta, and interleukin-6 (IL-6) production by ECs. Production was time-dependent. With RT-PCR, some cytokine mRNAs were detected in THP-1 and ECs after PMP stimulation. In relation to adhesiveness after PMP stimulation, we could clearly observe a shift in distribution not only of CD11b in THP-1 cells but also of CD54 in ECs. In addition, anti-P-selectin glycoprotein ligand-1 antibody reduced the expression of CD11b, CD32, and CD33 in THP-1 after PMP stimulation. These results suggest that high-shear-induced microparticles may contribute to the development of atherosclerosis and participate in vascular damage in inflammatory disorders.

Antigens, CD↗

PubMed2001

Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

Aged↗

PubMed2001

Health-related quality of life among dialysis patients in Seattle and Aichi.

We used the 36-item Short-Form Health Survey to compare health-related quality of life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in Aichi, JAPAN: Compared with Aichi patients, Seattle patients had lower scores on three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role-Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related to mental HRQOL were higher for Seattle patients compared with those of Aichi patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and Social Functioning did not differ significantly between the two groups. These differences persisted even after potential confounding factors were controlled for. However, after taking into account national norm data for the United States and Japan, differences in PF and VT disappeared, whereas differences in RP, RE, and MH persisted. These results suggest that the higher scores for PF and VT in Aichi patients were partly explained by the higher physical HRQOL of the Japanese general population. Although these data may not be representative of the total dialysis populations in the United States and Japan, they suggest potential differences in HRQOL between patients in the two countries. Additional research is needed to confirm these results and understand the factors associated with these differences. The findings suggest the need for further attention to the physical limitations of US dialysis patients and the mental health of Japanese dialysis patients.

Adult↗

PubMed2001

Protection of T cells from radiation-induced apoptosis by Cepharanthin.

Cepharanthin (CE) is a medicine that contains several biscoclaurine alkaloids. We examined the effects of CE on radiation-induced T cell apoptosis. Radiation induced apoptosis on T cells in a dose-dependent manner, while CE inhibited radiation-induced apoptosis. CE also attenuated the cytotoxic effects of radiation on the proliferative response of T cells. CE inhibited not only the loss of mitochondrial transmembrane potential but also the activation of caspase 3 in irradiated T cells. Radiation plus CE induced the up-regulation of Bax and the down-regulation of Bcl-2 in T cells in comparison with radiation alone. These results suggest that CE inhibits the signal transduction pathway of apoptosis induced by radiation, regardless of the expression of Bcl-2 or Bax.

Adult↗

PubMed2001

Translation, cultural adaptation, and initial reliability and multitrait testing of the Kidney Disease Quality of Life instrument for use in Japan.

BACKGROUND: The Kidney Disease Quality of Life instrument (KDQOL) consists of 79 items: 36 asking about health-related quality of life (HRQOL) in general (the Medical Outcomes Study SF-36) and 43 asking about QOL as it is affected by kidney disease and by dialysis. AIM: Translation, cultural adaptation and initial reliability and multitrait testing of the KDQOL for use in Japan. METHODS: Translation and cultural adaptation began with two translations into Japanese, two backtranslations into English, and discussions among the translators, the project coordinators in Japan, and the developers of the original (US-English) version. Focus-group discussions and field testing were followed by analyses of test-retest reliability, internal consistency, and convergent and discriminant construct validity. RESULTS: All eight of the SF-36 scales met the criterion for internal consistency (Cronbach's alpha ranged from 0.73 to 0.92) and were reproducible (intraclass correlations between test and retest scores ranged from 0.60 to 0.82). Of the 10 kidney-disease-targeted scales, only two had alpha coefficients of less than 0.70: 'sleep' (0.61) and 'quality of social interaction' (0.35). One item on the 'quality of social interaction' scale had a very weak correlation with the remainder of that scale (r = 0.10). Eliminating that item from scoring increased the alpha coefficient of the scale from 0.35 to 0.64. All three items on the 'quality of social interaction' scale had very strong correlations with other scales. CONCLUSIONS: First, in Japanese patients receiving dialysis the SF-36 scales are internally consistent and their scores are reproducible. Second, with the possible exception of the 'quality of social interaction' scale, the Japanese version of the KDQOL, can provide psychometrically sound kidney-disease-targeted data on quality of life in such patients.

Adult↗

PubMed2001

An autopsy case of giant cell myocarditis probably due to a non-steroidal anti-inflammatory drug.

An autopsy case of giant cell myocarditis (GCM) in a 74-year-old woman is presented. She suffered from hepatic dysfunction, skin eruption and disseminated intravascular coagulation due to the side-effects of a non-steroidal anti-inflammatory drug. After admission, heart failure progressed rapidly, and the patient died suddenly. At autopsy, her heart was slightly enlarged and the heart muscle was thickened with many small whitish nodules. She was diagnosed with GCM because of the infiltration of multinuclear giant cells, histiocytes, eosinophils and lymphocytes into the heart. We did not find any similar lesions in any other organs. Giant cell myocarditis, the etiology of which is not defined, is a rare disease with unfavorable prognosis. This case suggests the possibility of drug-induced GCM.

Aged↗

PubMed2001

Dialysis patients' preferences regarding cardiopulmonary resuscitation and withdrawal of dialysis in Japan.

The aim of this study is to show the preferences of Japanese dialysis patients for receiving cardiopulmonary resuscitation (CPR) in their current health status, if they were severely demented, or if they had terminal cancer and to determine their desires about continuing dialysis if they were severely demented or had terminal cancer. A questionnaire survey including the three scenarios was administered to 450 dialysis patients in 15 hospitals in JAPAN: Three hundred ninety-eight patients completed the questionnaires for a response rate of 88%. The majority of responding patients were men and were undergoing hemodialysis. Only 5% of the patients had discussed their preferences regarding CPR with their physicians, and 29%, with their family members. Forty-two percent of the patients answered that they would want to receive CPR if they experienced cardiopulmonary arrest in their current health status, and 12% answered in the affirmative if they were seriously demented or had terminal cancer. Eighteen percent of the patients would want to continue dialysis if they were demented, and 45%, if they had terminal cancer. Statistical analysis showed that more patients who were working tended to want to continue dialysis if they had terminal cancer than those who were not (53% versus 37%; P < 0.014). Patients' age and preferences did not statistically correlate. Preferences of Japanese dialysis patients for CPR and dialysis vary according to differences in health status, and only a minority would want to receive CPR for cardiopulmonary arrest even in their current health status.

Adult↗

PubMed2001

Effects of Saiko-ka-ryukotsu-borei-to in patients with hyperlipidemia.

We measured and compared levels of platelet-derived microparticles (PMPs), monocyte-derived microparticles (MMPs), CD62P on activated platelets, soluble E-selectin (sE-selectin), and anti-oxidized low density lipoprotein (LDL) antibody in hyperlipidemia patients and control subjects. Binding of anti-GPIIb/IIIa and anti-GPIb monoclonal antibodies to platelets was not significantly different between hyperlipidemia patients and controls. However, expression of CD62P on platelets and levels of PMPs were higher for hyperlipidemia patients than in controls, although the difference between groups in CD62P expression was not significant (PMPs: 534 +/- 63 vs. 388 +/- 47, p < 0.05; CD62P: 9.1% +/- 1.45 vs. 7.3% +/- 1.15, N.S.). Although there were no differences in expression of CD36 and CD40 by monocytes between the two groups, levels of MMPs were higher in hyperlipidemia patients than in controls (MMPs: 147 +/- 21 vs. 59 +/- 8, respectively, p < 0.01). Levels of anti-oxidized LDL antibody and sE-selectin were also higher in hyperlipidemia patients. We studied the effects of Saiko-ka-ryukotsu-borei-to on levels of these factors in patients with elevated triglyceride levels. After Saiko-ka-ryukotsu-borei-to treatment, levels of CD62P, PMPs, sE-selectin, and anti-oxidized LDL antibody were reduced significantly. Levels of triglycerides, total cholesterol and MMPs also decreased, but the changes were not significant. These findings suggest that Saiko-ka-ryukotsu-borei-to prevents the development of vascular complications in hyperlipidemia patients.

Aged↗

PubMed2001

Effect of bezafibrate on soluble adhesion molecules and platelet activation markers in patients with connective tissue diseases and secondary hyperlipidemia.

We evaluated the plasma concentrations of soluble adhesion molecules, platelet activation markers, and platelet-derived microparticles (PMPs) in patients with connective tissue diseases who had secondary hyperlipidemia caused by long-term steroid administration (n = 22) before and after treatment with bezafibrate. There were differences in levels of platelet activation markers both before and after treatment (platelet CD62p: 15.11+/-2.03 vs 10.38+/-8.53%, P < 0.05; platelet CD63: 12.12+/-9.17 vs 9.90+/-7.20%, P < 0.05). There were also differences in the levels of PMPs and soluble adhesion molecules both before and after treatment (PMP: 514+/-273 vs 401+/-201 /10(4) platelet. P < 0.05; soluble vascular cell adhesion molecule-1: 724+/-191 vs 666+/-157 ng/mL, P < 0.01). After 6 months of treatment, serum lipid concentrations were reduced by 9% for total cholesterol (TC) and 32% for triglyceride (TG). The level of PMPs, activated platelets, and soluble adhesion molecules were all significantly decreased after treatment with bezafibrate. These findings suggest that bezafibrate may be useful for inhibiting both PMP-dependent and -independent vascular damage in patients with connective tissue diseases complaining of secondary hyperlipidemia.

Bezafibrate↗

PubMed2001

Relationship between having a home doctor and outpatient utilization.

While universal insurance coverage should eliminate or substantially reduce financial and certain structural barriers to medical care, inequity in utilization of care may continue to exist. We conducted a questionnaire survey of a national random sample of 4500 Japanese age 16 or over in October, 1995. Separate analyses were conducted to predict the physician visit rates for the entire respondents (N=3395) and for those with chronic conditions (N=777). Forty-three percent of the total subjects reported an ambulatory physician visit within the past three months. About 17% of subjects with one chronic condition and 14% of those with two or more chronic conditions did not have any physician visits within recent three months. The regression model demonstrated that having a home doctor, as well as comorbidity and perceived health status, is significantly associated with outpatient visit both among all subjects (p < 0.0001) and among those with chronic conditions (p < 0.01). The Japanese health system still has unevenness in outpatient resource utilization. This mainly pertains to whether they have their own regular physician. The failure of some persons with chronic diseases to be seen requires further investigation.

Adolescent↗