Search

The purpose of this study was to clarify the current status of collaboration between nurses and community pharmacists as well as the requests and expectations that community pharmacists have of nurses in community-based comprehensive care systems. Questionnaires requiring open-ended responses were sent to 867 pharmacies throughout Fukushima prefecture (excluding four suspended pharmacies). We asked one pharmacist at each facility to answer the questions. We then analyzed the collected questionnaires using descriptive statistics, including the current status of nurse cooperation and the basic information about the pharmacies. Additionally, the open-ended descriptions of nurses' requests and expectations were analyzed quantitatively and qualitatively. The questionnaire collection rate was 32% (278 cases), and the breakdown of pharmacies that responded was 68.0% for facilities with 1 or 2 full-time pharmacists and 27.0% for facilities with 3 to 5 pharmacists. About 30% of respondents reported contact with the nursing profession at least once a week, while about 50% reported no contact at all or several times a year. The types of nurses collaborating with the pharmacies were clinic nurses (54.6%) and visiting nurses (43.4%). Some pharmacists had expected nurses to work cooperatively and rely on pharmacists. These results indicate that only about half of the pharmacists had opportunities to cooperate with nurses. For trust to be established between nurses and pharmacists, it is necessary for nurses to ask the pharmacists about medication and consult with them about patient medication management.

Rationale : Angiogenesis contributes to physiological and pathological conditions, including atherosclerosis. The Rap1 small G protein regulates vascular integrity and angiogenesis. However, little is known about the effectors of Rap1 involved in angiogenesis. It is not known whether afadin, an adherens junction protein that connects immunoglobulin-like adhesion molecule nectins to the actin cytoskeleton and binds activated Rap1, plays a role in angiogenesis. Objective : We investigated the role of endothelial afadin in angiogenesis and attempted to clarify the underlying molecular mechanism. Methods and Results : Treatment of human umbilical vein endothelial cells (HUVECs) with vascular endothelial growth factor (VEGF) and sphingosine 1-phosphate (S1P) induced the activation of Rap1. Activated Rap1 regulated intracellular localization of afadin. Knockdown of Rap1 or afadin by small interfering RNA inhibited the VEGF- and S1P-induced capillary-like network formation, migration, and proliferation, and increased the serum deprivation-induced apoptosis of HUVECs. Knockdown of Rap1 or afadin decreased the accumulation of adherens and tight junction proteins to the cell–cell contact sites. Rap1 regulated the interaction between afadin and phosphatidylinositol 3-kinase (PI3K), recruitment of the afadin–PI3K complex to the leading edge, and the activation of Akt, indicating the involvement of Rap1 and afadin in the PI3K–Akt signaling pathway. Binding of afadin to Rap1 regulated the activity of Rap1 in a positive-feedback manner. In vivo, conditional deletion of afadin in mouse vascular endothelium using a Cre-loxP system impaired the VEGF- and S1P-induced angiogenesis. Conclusions : These results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P-induced angiogenesis.

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.

Background/Aims Although mouse liver contains a large population of B cells, little is known about how hepatic B cells respond to bacterial lipopolysaccharide (LPS). Methods The cytokine and IgM productions of hepatic B cells were compared with those of splenic B cells. The effect of LPS-treated hepatic B cells on IFN-γ production from co-cultured NK1.1 + cells was also examined by irradiation and transwell experiments. Results Hepatic B cells stimulated with LPS produced substantial amounts of IFN-γ and IL-12 but a small amount of IgM, while splenic B cells did not produce any of these cytokines but produced a large amount of IgM. The hepatic B cells expressed surface markers similar to those on spleen B cells but expressed more C–X–C chemokine receptor 3 than spleen B cells. Notably, depletion of B220 + cells from liver MNCs (but not from spleen MNCs) greatly decreased LPS-induced IFN-γ production. Furthermore, LPS-treated hepatic B cells stimulated liver NK1.1 + cells to produce a remarkable amount of IFN-γ, not only through their soluble factors but also through direct cell–cell contact. Conclusions Liver B cells may play an important role in the defense against gram-negative bacterial infections by inducing IFN-γ production from liver NK cells.

Background: CD16+CD14+monocytes dramatically increase in number in patients with severe infection. Hemoperfusion with PMX-F (direct hemoperfusion with polymyxin B immobilized fibers) has been reported to be a safe and effective treatment for patients with septic shock, although the molecular mechanism that accounts for its effectiveness is still unclear. The purpose of this study was to quantify the number of CD16+CD14+monocytes in patients with an intra-abdominal infection and to evaluate the effects of PMX-F treatment on clinical parameters and leukocyte surface antigen expression in these patients.Materials and Methods : Seventeen septic patients who had an intra-abdominal infection were enrolled in this study; 7 of these patients received PMX-F treatment. Peripheral blood samples were obtained immediately after admission, and were also collected from the above 7 patients before, during, and immediately after their PMX-F treatment. The expression of CD14, CD16, and Toll-like receptor (TLR)-4 on these patients' monocytes was evaluated using flow cytometry. In addition, lipopolysaccharide (LPS)-induced production of TNF-α and IL-1β by these cells was measured by ELISA.Results: Monocytic expression of CD16 and TLR-4 was significantly greater in septic patients than in healthy controls, and their proportion of CD16+CD14+monocytes was similarly elevated. LPSinduced production of TNF-α and IL-1β by peripheral blood mononuclear cells (PBMCs) of septic patients was significantly reduced compared to controls. Furthermore, there was a reduction in the proportion of CD 16+CD 14+monocytes during PMX-F treatment, and in the expression of TLR-4 on monocytes after PMX-F treatment.Conclusions: These results showed that the number of peripheral blood CD16+CD14+monocytes and monocytic TLR-4 expression were markedly increased, and the production of pro-inflammatory cytokines in response to LPS significantly reduced in patients with sepsis. PMX-F treatment was found to be effective in reducing the number of CD 16+CD 14+monocytes and in decreasing the monocytic expression of TLR-4 in patients with septic shock.

Background. The Japanese Gastric Cancer Association’s (JGCA’s) Gastric cancer treatment guidelines for doctors’ reference and the guidelines (GLs) for popular use were both published in 2001. The purpose of this study was to know whether or not it is useful for patients to read the GLs for popular use. Methods. We lent the GLs for popular use to patients with gastric cancer for several days and had them read the GLs before they were informed about their condition and the recommended treatment. Then they received questionnaires concerning the GLs. Results. Most of the patients, even the elderly, had read and understood the GLs. Nearly 70% of the patients answered that it was very useful for them to read the GLs. On the other hand, 34% of the patients suggested negative aspects, such that reading the GLs increased their anxiety about the disease or treatment. Only 9% of the patients expected treatment that followed the GLs, whereas 54% of the patients expected treatment based on the doctor’s own experience without adherence to the GLs. If the doctor were to suggest treatment that did not follow the GLs, 87% of the patients answered that they would follow the doctor’s suggestion, and it was only 8% who answered that they would seek a second opinion. These results did not differ when patients were requested to fill out questionnaires anonymously. Conclusion. Although the GLs for popular use are useful to provide patients with information concerning the disease and the treatment modalities, they may not have a great impact on patients’ decisions about their treatment.

Background. Acute lung injury is a frequent extraabdominal complication of bacterial peritonitis, and neutrophil plays an important role in this lung damage. Macrophage inflammatory protein 2 (MIP-2) serves the same chemotactic function as IL-8 which is a potent neutrophil chemotactic factor in humans, and we investigated the role of MIP-2 associated with neutrophil recruitment in the lung of murine peritonitis. Methods. Cecal ligation and puncture (CLP) were performed on mice. MIP-2 levels in blood and lung tissue, MIP-2 mRNA expression in lung tissue and bronchoalveolar lavage fluid (BALF), and CD11b expression on peripheral blood neutrophil and BALF cells were determined after CLP. In addition, we investigated the effect of anti-MIP-2 antibody on the lung injury associated with peritonitis. Results. MIP-2 mRNA expression was observed in lung tissue after CLP and numerous neutrophils were accumulated in the lung under those conditions. Anti-MIP-2 antibody contributed to the inhibition of the CD11b expression and chemotaxis of pulmonary neutrophils, lung edema, and thus the reduction in peritonitis-related mortality. Conclusions. MIP-2 plays a pivotal role in neutrophil recruitment in the lung following peritonitis, and control of neutrophil accumulation in the lung by neutralizing MIP-2 is recommended as a new therapeutic approach to the lung damage associated with peritonitis.

The level of serum CCL5, a C-C chemokine, is reportedly correlated with tumor progression in several cancers. We herein investigated the mechanisms by which CCL5 might contribute to tumor progression in gastric cancer. Serum CCL5 levels significantly correlated with tumor progression and prognosis in patients with gastric cancer. Immunohistochemistry showed that tumor-infiltrating lymphocytes expressed CCL5, while the tumor cells expressed the CCL5 receptors. Fluorescent double staining showed that tumor-infiltrating CD4+ cells rather than CD8+ cells preferentially expressed CCL5. Using gastric cancer cell lines (MKN45, KATO III), we examined CCL5 production by coculturing whole peripheral blood mononuclear cells (PBMCs), CD4+ cells, or CD8+ cells, with tumor cells. CD4+ cells cocultured with tumor cells remarkably enhanced CCL5 production in a direct cell-cell contact manner over other cocultured PBMCs, including CD8+ cells. Gastric cancer cell lines expressed CCL5 receptors and augmented their proliferation in response to CCL5 stimulation. Furthermore, we examined the effect of CCL5-treated cancer cells on the cocultured PBMCs, focusing on the CD4+/CD8+ proportion and apoptosis. Coculture of CCL5-treated gastric cancer cells with PBMCs resulted in a significant decrease in the proportion of CD8+ cells but not CD4+ cells, suggesting Fas-FasL-mediated apoptosis in CD8+ cells. In immunodeficient mice coinjected with KATO III and PBMCs, neutralization of CCL5 significantly suppressed tumor progression, resulting in a favorable outcome. In conclusion, gastric cancer cells might thus induce CD4+ T cells to secrete CCL5 and exploit it for their progression, as well as to aid in the prevention of CD8+ T cell-involved tumor elimination.

Background: Granulysin is a cytolytic molecule present in human cytotoxic T cells and natural killer cell granules, and plays a key role in the cell-mediated immunity against tumor and infection. However, few studies have estimated serum granulysin concentrations in patients with solid or hematological malignancies. Methods: Peripheral blood samples were taken from patients with gastric carcinoma preoperatively and from healthy volunteers. Serum and tumor tissue granulysin concentrations were measured using a granulysin-specific ELISA kit in order to assess its prognostic value. Results: Both serum and tumor tissue granulysin concentrations were higher in patients with stage II or III gastric cancer and lower in patients with stage IV disease as compared to healthy controls. The low preoperative granulysin levels were associated with more frequent hepatic and peritoneal metastases, and with a poor outcome of the curative gastrectomy. Conclusions: Preoperative serum granulysin levels reflect the status of cell-mediated immunity in patients with gastric carcinoma. It has significance as a prognostic determinant following a curative resection.

Backgrounds Toll-like receptor (TLR)-9 plays a critical role in the recognition of the CpG motifs, which is frequently observed in bacterial DNA. To date, there have not been any reports regarding the role of bacterial DNA in the systemic circulation on the development of sepsis. Methods We examined the expression of TLR-9 in the liver and spleen in a murine peritonitis model (CLP mice). We also measured the cytokine response of mononuclear cells (MNCs) from normal and CLP mice to CpG oligodeoxynucleotides (ODN) in vitro and in vivo . Results TLR-9 expression on F4/80 + and NK1.1 + CD3e + cells in the liver of CLP mice was elevated compared to sham-operated mice. With regard to cytokine production, we found that CpG ODN markedly stimulated the production of inflammatory cytokines by murine macrophages and liver MNCs. The intravenous injection of CpG ODN in mice that underwent CLP 12h earlier led to their increased cytokine production and their increased mortality. In addition, the depletion of NK/NKT cells contributed to improve their survival rate. Conclusions Our results suggest that, in patients with overwhelming bacterial infection, bacterial DNA may induce liver toxicity that is mediated by liver NKT cells and macrophages that express high levels of TLR-9.

In addition to natural killer (NK) cells, T cells expressing natural killer cell markers, CD56 or CD57 (NK type T cells), have been considered to play an important role in antitumor immunity. We examined the proportion of NK cell and NK type T cell subsets in the peripheral blood from patients with gastric cancer. The IFN-gamma production capacity and population of cytoplasmic perforin positive cells in peripheral blood mononuclear cells (PBMC) were evaluated. Peripheral blood samples were obtained from 56 patients with gastric cancer and 21 healthy volunteers. The proportion of CD56- CD57+ T cells (CD57+ T cells) was significantly higher in advanced gastric cancer patients than those in healthy volunteers and patients with early stage gastric cancer, whereas no correlation was observed between the proportion of CD56+ T cells or NK cells and tumor progression. Furthermore, a significant decrease of CD8+ CD57+ T cells was found in patients with advanced gastric cancer. The proportion of CD57+ T cells did not correlate with interferon-gamma (IFN-gamma) production from PBMC in gastric cancer patients, although a significant correlation was found between them in healthy volunteers. The proportion of perforin positive CD57+ T cells, especially CD8+ CD57+ T cells, in patients with gastric cancer was markedly lower than that in healthy volunteers. Collectively, although the proportion of CD57+ T cells in PBMC was found to increase with tumor progression, their function in antitumor immunity is impaired in patients with gastric cancer.

Although the peritoneal cavity (PC) is the most common site of metastasis in gastric carcinoma, its immune status in patients with advanced cancer remains largely unknown. We investigated the relationship between clinical parameters and cytokine levels in the PC and also evaluated IFN-y production by peritoneal exudate cells (PEC), obtained during surgery from patients with stage III-IV gastric carcinoma. Although the IFN-gamma and IL-12 levels in the PC did not differ between stage III and stage IV cancer patients, the latter had higher levels of IL-10 and IL-18. Those patients with higher IFN-gamma levels experienced a significantly better survival-rate than those with lower IFN-gamma levels, whereas IL-18 (but not IL-10) levels were inversely-correlated with survivaL IFN-gamma levels increased in parallel with IL-18 levels in patients who survived more than two years, but this correlation did not apply to patients who died of disease within two years. In addition, anti-CD3-Ab or cytokine- stimulated PEC from patients with low IL-10 levels in their PC produced a significantly greater amount of IFN-gamma than PEC from patients with high PC IL-10 levels. In conclusion, a high level of IFN-y in the PC is an indicator of favorable outcome. Both IL-10 and IL-18 levels in the PC increased with tumor progression. Although the number of PEC capable of producing IFN-gamma increases with tumor progression, their ability to secrete IFN-gamma in response to IL-18 may be influenced by local IL-10 levels in the PC.

The aim of this study was to determine whether the cytologic features of cancer cells in the peritoneal lavage fluid from patients undergoing surgery for gastric cancer affect prognosis. A total of 141 patients with stage III-IV gastric cancer were enrolled in this study. Among 111 patients without peritoneal metastasis (P0), 43 were noted to have positive peritoneal cytology (P0/CY1). These patients were subclassified into two groups according to the cluster formation of cancer cells in the cytology specimen, namely, 17 with cluster formation and 26 without cluster formation. The clinicopathologic parameters and survival rates were compared between these two groups. Among the P0/CY1 patients, no significant difference in clinicopathologic features existed between patients with or without the cluster formation of cancer cells. However, the survival rate of patients without cluster formation was significantly higher than that of those with cluster formation. Furthermore, the survival curves of patients without cluster formation was similar to that of the P0/ CY0 patients with stage IV cancer. Subclassification according to the presence or absence of the cluster formation of cancer cells may be useful for predicting the outcome of patients with positive cytology after surgery for advanced gastric cancer.

BACKGROUND Interleukin-18 (IL-18), a recently described cytokine produced mainly by macrophages, stimulates interferon-γ (IFN-γ) production by natural killer cells and T cells. Although it has been reported that serum IL-18 levels are higher in patients with advanced tuberculosis and acute graft-versus-host disease compared with normal controls, the authors found no reports regarding serum IL-18 levels in patients with malignant solid tumors. The purpose of this study was to determine serum IL-18 levels and their clinical significance in patients with gastric carcinoma. METHODS Peripheral blood samples were obtained from 94 patients with gastric carcinoma who underwent curative surgery and from 50 healthy volunteers. The serum IL-18 level, the IFN-γ, level, and the Helicobacter pylori (HP) serology status were determined in each sample with an enzyme-linked immunosorbent assay. RESULTS The mean serum IL-18 level for all patients was significantly higher compared with the mean level in healthy volunteers (P < 0.01). IFN-γ titers were below the level of detection in all samples tested. When the patients were subdivided into groups, it was found that the serum IL-18 level in patients with Stage II and III disease was significantly higher compared with the level found in healthy volunteers (P < 0.01). The serum IL-18 level decreased after patients underwent surgical resection. However, there was no significant difference in the serum IL-18 level between healthy controls and patients with Stage I or IV disease. Patients with IL-18 levels ≥ 310 pg/mL (i.e., equal to or greater than the mean levels ± 1 standard deviation in the healthy volunteers) experienced a significantly lower survival rate compared with patients who had IL-18 levels < 310 pg/mL after undergoing surgery (P < 0.05) despite a lack of any discernible difference in clinicopathologic factors between the two groups. The serum IL-18 level was identified as an independent postoperative prognostic factor in multivariate survival analysis using a Cox proportional hazards model (hazard ratio, 4.89; P = 0.01). There was no significant correlation between HP serology status and serum IL-18 levels. CONCLUSIONS The preoperative serum IL-18 level may represent a significant postoperative prognostic determinant in patients with gastric carcinoma. Its function in the host immune system remains to be elucidated. Cancer 2001;92:2050–5. © 2001 American Cancer Society.

Background and Objectives: Immune status in the peritoneal cavity of patients with gastric cancer remains largely unknown. To clarify the clinical significance of the host immune response within the peritoneal cavity, we examined the levels of interferon-gamma (IFN-γ), a type 1 cytokine, and interleukin-10 (IL-10), a type 2 cytokine, in peritoneal washings obtained from patients with gastric cancer. Methods: Both the concentrations of IFN-γ and of IL-10 in peritoneal washings obtained during surgery from 56 patients with gastric cancer were determined by an enzyme-linked immunosorbent assay. Results: The IFN-γ level was not correlated with the IL-10 level. The IL-10 level increased in a stage-dependent manner. The high IL-10 level correlated with an unfavorable outcome, whereas there was no relationship between the IFN-γ level and survival rate. However, among the stage III–IV cancer patients, the high IFN-γ level correlated with a favorable outcome, while there was no relationship between the IL-10 level and survival rate. Conclusion: Although the IL-10 level increases with tumor progression, the outcome of patients with advanced gastric cancer may be affected by the IFN-γ level, but not by the IL-10 level, in the peritoneal cavity. J. Surg. Oncol. 2001;78:124–130. © 2001 Wiley-Liss, Inc.

Fas ligand (FasL), which induces apoptosis against Fas-expressing cells, has been found to be expressed on various cell types including cancer cells. Membrane-bound FasL is cleaved to release soluble FasL (sFasL). Although serum or plasma sFasL concentration has been reported to increase in various diseases, sFasL concentration in healthy normal persons has not been fully studied. There have been few reports on sFasL concentrations in patients with carcinomas. We measured plasma sFasL concentrations using an enzyme-linked immunosorbent assay in 155 healthy volunteers (70 males and 85 females with an average age of 41.5+/-15.4) and 112 patients with gastric carcinoma (76 males and 36 females with an average age of 62.3+/-11.5). A significant negative correlation existed between age and plasma sFasL concentration in healthy volunteers. sFasL concentrations in males were significantly lower than those in females. Plasma sFasL levels were significantly higher in patients with gastric carcinoma than in healthy volunteers when male subjects aged 50 or older were analyzed, although no significant difference existed between the groups in the age bracket of 35 to 49. Male patients aged 50 or older with stage 1B or 2 tumors showed significantly higher plasma sFasL concentrations than those with stage 1A tumors or those with stage 3 or 4 tumors. In conclusion, age- and gender-matched controls should be used when plasma sFasL concentration is investigated. The origin and physiological or clinical significance of plasma sFasL in healthy volunteers and gastric cancer patients remain to be clarified.

Tissue specimens from patients with the scirrhous type of gastric carcinoma were stained using the peroxidase-antiperoxidase (PAP) method. Nine out of thirty-seven specimens (24 per cent) showed positive estrogen staining, and here tissues from male or older patients were usually stained. Cumulative survival rate in patients whose tissue showed a positive estrogen staining was higher than that in case of a negative estrogen staining. Four out of thirty-one specimens (13 per cent) stained positively for progesterone, all four patients being male. These results suggest that estrogen and progesterone may relate to the growth of the scirrhous type of gastric cancer.

In this study, the clinical significance of the tumor markers, tissue polypeptide antigen (TPA) and lipid-bound sialic acid (LBSA) in conjunction with carcinoembryonic antigen CEA, was tested in 52 gastric cancer patients. The incidence of elevated serum levels of these 3 markers was as follows: 63% (33/52) for TPA; 40% (21/52) for LBSA; 21% (11/52) for CEA. In a combination assay using all three tumor markers, 37 out of 52 gastric cancer patients (71%) showed a positive combination assay, while 5 out of 20 normal subjects (25%) showed a positive combination assay. In a discriminant analysis of the resulting data, 18 out of 52 gastric cancer patients (35%) were classified correctly based on an analysis of CEA alone. Furthermore, 25 out of 52 gastric cancer patients (48%) and all 20 normal subjects (100%) were classified correctly based on an analysis of all three variables. Our data suggest that TPA and LBSA are more sensitive than CEA as markers of gastric cancer, and that the simultaneous measurement of TPA and LBSA in conjunction with CEA is more useful in cancer detection than the measurement of CEA alone.

This report describes an adrenal myelolipoma occurring in a 39-year-old man first noted incidentally by computed tomography (CT). The radiographic findings of this neoplasm are briefly discussed and magnetic resonance (MR) imaging of myelolipoma is also described. Myelolipomas can be distinguished from nonfunctioning adenomas by differences in signal intensity on T2-weighted images.