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Biomedical subjects

Akio Hiraki

Publications and source records attributed to Akio Hiraki.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Diagnosis and treatment of tuberculous pleurisy--with special reference to the significance of measurement of pleural fluid cytokines].

Tuberculous pleurisy as well as malignant pleuritis is a representative disease presenting pleural effusion. The diagnosis of tuberculous pleurisy is made from examination of pleural effusion, but the sensitivity of smear or culture of Mycobacterium tuberculosis from pleural fluid is generally low. Although the pleural fluid concentration of adenosine deaminase (ADA) is useful in terms of sensitivity or specificity, the value could be high in empyema or rheumatoid pleuritis. Thoracoscopic biopsy of pleura is more sensitive rather than conventional percutaneous needle biopsy, but is more invasive. Tuberculous pleural effusion is caused by delayed allergy which macrophage and T-helper 1 cells mainly relate and the stimuli of bacterial body consecutively induces T-helper 1 cytokines. Pleural fluid interferon-gamma (INF-gamma) is important not only in pathogenesis but also in diagnosis. We demonstrated that INF-gamma is a more sensitive and specific indicator for tuberculous pleurisy than ADA using receiver operating characteristics (ROC) analysis. Cytometric bead array (CBA) is a tool to simultaneously measure abundance of various cytokines and is expected to be a very useful method to provide informations for understanding a feedback mechanism of cytokine network. It is needed to clear the immunity in pleural fluid and to establish the less invasive and more useful method to diagnose tuberculous pleurisy.

Adenosine Deaminase↗
PubMed2003

Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells.

We have shown previously that KIAA0223, a gene encoding a minor histocompatibility antigen, HA-1, whose expression was believed to be restricted to the hematopoietic cells, is aberrantly expressed in some solid tumor cell lines. However, its significance in tumor immunity needs to be determined. Cytotoxic activity of HA-1(H)-specific cytotoxic T lymphocytes (CTLs) was assessed against solid tumor cell lines expressing KIAA0223 using (51)Cr release assays. Five of seven cell lines were lysed when HLA-A*0201 was adequately expressed. One of the two CTL-resistant cell lines became susceptible after treatment with IFN-gamma and TNF-alpha, while the other was lysed only after pulsing with HA-1(H) peptide. In most cell lines tested, HA-1(H) peptide was properly generated and presented for recognition by the CTL. However, impaired antigen processing and presentation observed in this study may result in escape from CTL recognition in vivo, as well as in vitro, as observed in this study.

Gene Expression Regulation, Neoplastic↗
PubMed2003

Human herpes virus-8-negative primary effusion lymphoma in a patient with common variable immunodeficiency.

Primary effusion lymphoma (PEL) is a newly described high-grade B cell lymphoma developing in association with human herpes virus type 8 (HHV-8) in human immunodeficiency virus (HIV)-infecting individuals. Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by reduced serum immunoglobulin and heterogeneous clinical features. The risk of cancer in CVID patients is increased. Here, we describe a PEL that developed in the pleural and pericardial cavities of an HIV-negative and HHV-8-negative patient with CVID.

Common Variable Immunodeficiency↗
PubMed2003

Diagnostic significance of interferon-gamma in tuberculous pleural effusions.

STUDY OBJECTIVES: Tuberculosis (TB), the single most frequent infectious cause of death worldwide, also is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Differential diagnosis between TB and nontuberculous pleural effusion can be sometimes difficult, representing a critically important clinical problem. METHODS: We studied 46 patients presenting with pleural effusion to the National Sanyo Hospital between April 2000 and January 2001 (34 men and 12 women; mean age, 64 years). Ten patients (22%) had tuberculous pleurisy, 19 patients (41%) had malignant pleuritis, and 17 patients (37%) had pleural effusion due to an etiology other than tuberculosis or cancer. Pleural fluid concentrations of four suggested markers were measured using commercially available kits. RESULTS: The pleural fluid levels (mean +/- SE) of adenosine deaminase (83.3 +/- 18.2 U/L vs 25.8 +/- 20.4 U/L, p < 0.0001), interferon-gamma (137 +/- 230 IU/mL vs 0.41 +/- 0.05 IU/mL, p < 0.0001), immunosuppressive acidic protein (741 +/- 213 micro g/mL vs 445 +/- 180 micro g/mL, p < 0.001) and soluble interleukin 2 receptor (7,618 +/- 3,662 U/mL vs 2,222 +/- 1,027 U/mL, p < 0.0001) were significantly higher for tuberculous pleuritis than for other causes of effusion. Receiver operating characteristic analysis demonstrated that pleural fluid content INF-gamma was the best indicator of tuberculous pleurisy among four relevant biological markers. CONCLUSIONS: INF-gamma in pleural fluid is the most sensitive and specific among four biological markers for tuberculous pleuritis. Thus, our results suggest that determination of INF-gamma at the onset of pleural effusion is informative for the diagnosis of tuberculous pleuritis. Further studies including larger numbers of patients are needed to verify this result.

Adenosine Deaminase↗
PubMed2003

Relative abundance and patterns of correlation among six cytokines in pleural fluid measured by cytometric bead array.

Several cytokines play significant roles in the development and pathogenesis of pleural effusion. Little is known, however, about possible interactions between individual cytokines in terms of regulation of their relative abundance in the effusion. We studied 93 patients presenting with pleural effusion to the National Sanyo Hospital (68 men and 25 women; mean age, 64 years). Twenty-two patients had tuberculous pleurisy, 40 had malignant pleuritis, and 31 had effusions due to an etiology other than tuberculosis or cancer (miscellaneous). Pleural fluid concentrations of IL-2, IL-4, IL-5, IL-10, TNF-alpha, and INF-gamma were simultaneously measured by cytometric bead array (CBA). The ratios of IL-4/IL-5, IL-4/TNF-alpha, IL-2/TNF-alpha, and IL-10/TNF-alpha were lower in patients with tuberculosis pleurisy compared with other patients. In all three groups of patients significant correlation was seen between abundance of IL-2 vs. IL-4, IL-5, IL-10, or TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In malignant pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, TNF-alpha, or INF-gamma, between IL-4 vs. INF-gamma, and between TNF-alpha vs. INF-gamma. In tuberculosis pleural fluid patients, the significant correlation was between IL-2 vs. TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma. In miscellaneous pleural fluid patients, the significant correlation was between IL-2 vs. IL-4, IL-10, or TNF-alpha, between IL-4 vs. IL-10, TNF-alpha, and between IL-10 vs. TNF-alpha. No significant correlation was observed between other pairs of cytokines. Strong correlation in abundance between particular cytokines in pleural fluids suggests cross-talk between them, in terms that an altered level of one of them provides a feedback mechanism regulating synthesis and/or secretion of another one. Such interactions may play important roles in pathogenesis and severity of the effusion. The CBA methodology provides a convenient tool to investigate these interactions.

Adenosine Deaminase↗
PubMed2003

[Rifampicin-induced severe thrombocytopenia in a patient with miliary tuberculosis].

A 74-year-old female visited a local clinic complaining of fever on January 21, 2002. A chest X-ray and a chest computed tomography (CT) showed diffuse micronodules in all lung fields, which strongly suggested miliary tuberculosis. On January 23, she was referred to our hospital for further examinations. Though sputum was negative on smear, culture, and polymerase chain reaction (PCR) for M. tuberculosis, bone marrow aspirate examined on admission revealed epithelioid granuloma. Therefore we diagnosed her as a miliary tuberculosis, and she was treated with 300 mg of Isoniazid (INH), 450 mg of Rifampicin, and 750 mg of Streptomycin (SM) daily. Five days later, severe thrombocytopenia (platelet count 0.3 x 10(4)/microliter) was observed. We immediately discontinued all antituberculous drugs and administered concentrated platelets and immune globulin. Platelet-associated IgG was detected, and megakaryocytes were slightly increased in moderately hypocellular marrow on the bone marrow aspirate examined again after the appearance of thrombocytopenia. Eleven days after discontinuing all antituberculous drugs, platelet count recovered to 10.2 x 10(4)/microliter. INH, SM, Levofloxacin (LV) were administered afterward, and these drugs did not induce thrombocytopenia. Though challenge administration of RFP was not performed, we concluded that the thrombocytopenia was immunologically induced by RFP. We should keep in mind that RFP-induced thromobocytopenia could appear in the first week after the initiation of therapy.

Aged↗
PubMed2002

Enhanced induction of human WT1-specific cytotoxic T lymphocytes with a 9-mer WT1 peptide modified at HLA-A*2402-binding residues.

The Wilms' tumor gene WT1 is overexpressed in most types of leukemias and various kinds of solid tumors, including lung and breast cancer, and participates in leukemogenesis and tumorigenesis. WT1 protein has been reported to be a promising tumor antigen in mouse and human. In the present study, a single amino-acid substitution, M-->Y, was introduced into the first anchor motif at position 2 of the natural immunogenic HLA-A*2402-restricted 9-mer WT1 peptide (CMTWNQMNL; a.a. 235-243). This substitution increased the binding affinity of the 9-mer WT1 peptide to HLA-A*2402 molecules from 1.82 x 10(-5) to 6.40 x 10(-7) M. As expected from the increased binding affinity, the modified 9-mer WT1 peptide (CYTWNQMNL) elicited WT1-specific cytotoxic T lymphocytes (CTL) more effectively than the natural 9-mer WT1 peptide from peripheral blood mononuclear cells (PBMC) of HLA-A*2402-positive healthy volunteers. CTL induced by the modified 9-mer WT1 peptide killed the natural 9-mer WT1 peptide-pulsed CIR-A*2402 cells, primary leukemia cells with endogenous WT1 expression and lung cancer cell lines in a WT1-specific HLA-A*2402-restricted manner. These results showed that this modified 9-mer WT1 peptide was more immunogenic for the induction of WT1-specific CTL than the natural 9-mer WT1 peptide, and that CTL induced by the modified 9-mer WT1 peptide could effectively recognize and kill tumor cells with endogenous WT1 expression. Therefore, cancer immunotherapy using this modified 9-mer WT1 peptide should provide efficacious treatment for HLA-A*2402-positive patients with leukemias and solid tumors.

HLA-A Antigens↗
PubMed2002

Parathyroid hormone-related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia.

BACKGROUND: Parathyroid hormone-related protein (PTH-rP) is a major cause of tumor-induced hypercalcemia (TIH) and frequently is found to be elevated in serum of patients with TIH. In the current study, the authors examined the usefulness of PTH-rP measurement at the time of first presentation in the follow-up of lung carcinoma patients with TIH. METHODS: The authors retrospectively studied 23 of 1149 lung carcinoma patients who were found to have TIH at the time of first presentation for the correlation between serum PTH-rP and the development of bone metastases and survival compared with lung carcinoma patients without TIH who were matched by gender, age, Eastern Cooperative Oncology Group performance status, histological type of tumor, and stage of the disease. RESULTS: Twenty-three lung carcinoma patients with TIH demonstrated significantly increased serum levels of PTH-rP (mean +/- standard error [SE], 84.1 +/- 16.5 pmol/L) compared with control patients without TIH (mean +/- SE, 36.2 +/- 2.0 pmol/L) at the time of first presentation, (P < 0.001). In these hypercalcemic patients, patients whose serum PTH-rP was > 150 pmol/L (n = 16) were found to have a significantly increased rate of bone metastases (71.4% vs. 12.5%; P = 0.01) and decreased survival (median survival of 1.4 months vs. 5.4 months; P < 0.015) compared with patients whose serum PTH-rP was < 150 pmol/L (n = 7). CONCLUSIONS: The data from the current study suggest that serum PTH-rP as determined at the time of first presentation is a useful indicator of not only hypercalcemia but also bone metastasis and eventual survival in patients with lung carcinoma.

Adult↗
PubMed2002

Expression of minor histocompatibility antigen, HA-1, in solid tumor cells.

BACKGROUND: Minor histocompatibility antigen (mHag) induces and mounts graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Among several mHags, HA-1 is one that acts alone and is the most studied. It is suggested that HA-1 may be one of the immunodominant antigens inducing not only graft-versus-host disease but also graft-versus-malignancy effects. There are some reports that mHag HA-1-specific cytotoxic T lymphocytes generated from an HA-1-negative donor can lyse HA-1-positive leukemic cells. However, the tissue distribution of HA-1 has been described as restricted to the cells of the hematopoietic lineage. METHODS: We examined the HA-1 expression in peripheral blood mononuclear cells (PBMNC), leukemia/lymphoma cell lines, solid tumor cell lines, and paired samples of tumor and normal tissues from individual cancer patients by quantitative reverse-transcription polymerase chain reaction. RESULTS: We found that mRNA of HA-1 is expressed in all leukemia/lymphoma cell lines and PBMNC. Most of the leukemia/lymphoma cell lines have the same levels of HA-1 expression as a leukemia/lymphoma cell line, Raji. The expression levels of human PBMNC were 14- to 19-fold higher than those of Raji. Among 32 solid tumor cell lines, 7 showed >50% expression levels compared with Raji. CONCLUSIONS: HA-1 expression in the mRNA level is higher in cells of hematopoietic origin, but this tissue distribution is not strictly restricted. Some solid tumor cells and tissues express HA-1 gene equal to hematopoietic cells.

Base Sequence↗
PubMed2002

Interleukin-12 augments cytolytic activity of peripheral blood mononuclear cells against autologous lung cancer cells in combination with IL-2.

The majority of patients with advanced lung cancer die within a few years. Accordingly, new therapeutic modalities need to be developed. Interleukin (IL)-12 was previously known as natural killer (NK) cell stimulatory factor or cytotoxic lymphocyte maturation factor. By virtue of its effects on T cells and NK cells, IL-12 seems to be one of the key cytokines that regulates cell-mediated anti tumor immune responses. Recently, there has been a substantial interest in the potential applications of IL-12 in the treatment of lung cancer. However, there have been no reports about the effect of IL-12 on peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients in an autologous setting. In this study, we examined the cytotoxicity of PBMC activated by IL-2, IL-12 or both against K562 or autologous lung cancer cells. In contrast to the effect of IL-2 on NK activity, IL-12 alone augmented NK activity against K562 cells, but not against autologous lung cancer cells. IL-12 augmented the IL-2 mediated cytotoxicity of PBMC against both K562 and autologous lung cancer cells. In the absence of IL-2, IL-12 alone cannot induce an autologous anti-tumor effect in vivo. In summary, our results clearly demonstrated that IL-12 can augment the cytolytic activity of PBMC against K562 and autologous lung cancer cells when combined with IL-2, although, IL-12 alone was unable to induce a marked increase in the cytotoxicity against autologous lung cancer cells. These results suggest that an administration of IL-12 in combination with IL-2 may be a useful therapeutic option for solid tumors.

Aged↗
PubMed2002

Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy.

We established several in vitro drug-resistant cell lines after continuous, long-term exposure of each drug to elucidate mechanisms of drug resistance. Whether drug resistance in these in vitro resistant cell lines reflects clinical drug resistance still remains unanswered. In this study, a pair of lung cancer cell lines was established from one patient with squamous cell carcinoma of the lung, with one line being established before and one line after combination chemotherapy (cisplatin/ifosfamide/vindesine). Combination chemotherapy selected resistant EBC-2/R cells, which showed cross-resistance to 4-hydroxyifosfamide (3.2-fold), cisplatin (2.3-fold), and methotrexate (3.7-fold) and collateral sensitivity to vindesine (0.77-fold) compared with parent EBC-2 cells. EBC-2/R cells showed decrease in intracellular accumulation of cisplatin, increase in intracellular concentration of glutathione (GSH), and overexpression of multidrug resistance-associated protein (MRP) 3 when compared with EBC-2 cells. A single cycle of chemotherapy was not sufficient to select other mechanisms of drug resistance, such as multidrug resistance-1/P-glycoprotein, MRPs 1, 2, 4, and 5, lung resistance-related protein, metallothionein IIa, glutathione S-transferase pi, gamma-glutamylcysteine synthetase (light and heavy chain), and excision repair cross complementing 1. Sequentially we established two cell lines, which cell lines showed the differences of the cisplatin resistance, expression level of MRP3, intracellular GSH level and intracellular accumulation of cisplatin. A pair of cell lines will be useful to elucidate resistant mechanisms of cisplatin in heterogeneous lung cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Differentiation of monoblastic cell line UG3 into leukemic dendritic cells.

Dendritic cells (DCs) are known to be generated from leukemic clone from patients with acute and chronic leukemia when cultured in the presence of combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4. However, there have been few reports that showed DCs could be effectively differentiated from human leukemia cell lines. In this study, we have shown that a human monoblastic cell line, UG3, was inducible to differentiate into DCs in the presence of GM-CSF and TNF-alpha along monocyte-macrophage lineage. These DCs, consistently displayed dendritic morphology, phenotypes and allogeneic T-cell stimulating capacity. UG3 cells thus may represent a suitable model to further elucidate characteristics of DC differentiation.

Antigen Presentation↗
PubMed2002

Antilung cancer effect of WT1-specific cytotoxic T lymphocytes.

We and other groups have recently reported that CTLs that specifically recognize a peptide derived from WT1 lyse leukemia cells in a HLA class I-restricted manner. Because WT1 is expressed in various solid tumors as well as in leukemic cells, we investigated whether WT1-specific CTLs can also inhibit the growth of lung cancer by examining their cytotoxic activity against lung cancer cell lines in vitro and their inhibitory effect on the growth of human lung cancer cells engrafted into nude mice. The WT1 transcript was detected in most of the lung cancer cell lines examined. A WT1-specific, HLA-A24-restricted CTL clone (designated TAK-1) exhibited cytotoxicity against lung cancer cell lines bearing HLA-A24 but did not lyse cells lacking this HLA. This suggests that the target antigen for TAK-1 on HLA-A24-positive lung cancer cells is the naturally processed WT1 peptide. Adoptive transfer of TAK-1 into nude mice that had been engrafted with a HLA-A24-positive lung cancer cell line resulted in inhibition of cancer cell growth and prolonged survival. These findings strongly suggest that WT1 is a universal tumor-associated antigen and that WT1-targeting immunotherapy offers a potentially effective treatment option for lung cancer as well as leukemia.

Animals↗
PubMedDate not supplied

Thrombocytosis as a useful prognostic indicator in patients with lung cancer.

BACKGROUND: Thrombocytosis can accompany various cancers including lung cancer. This finding has recently been suggested to indicate poor prognosis. OBJECTIVES AND METHODS: We retrospectively examined the clinical records of 611 patients with lung cancer to investigate whether there is a correlation between thrombocytosis, other clinicopathologic factors, and survival. RESULTS: Ninety-eight of the patients (16%) manifested thrombocytosis at the time of their first evaluation at our hospital. Thrombocytosis and age (p = 0.0006) and thrombocytosis and performance status (p = 0.0002) are significantly correlated, but thrombocytosis is not related to gender, tumor histology, clinical stage, or serum lactate dehydrogenase concentrations. Survival is significantly shorter in patients with thrombocytosis: [median survival time (MST) 7.5 months; n = 98] than without thrombocytosis (MST 10.1 months; n = 513; p = 0.0029). Multivariate analysis of prognostic factors using the Cox proportional hazards model indicated that thrombocytosis had independent prognostic significance. CONCLUSION: Thrombocytosis at the first patient evaluation is an independent prognostic factor in lung cancer.

Adult↗
PubMedDate not supplied

Gingival metastasis in lung cancer.

Gingival metastasis is an extremely rare manifestation of lung cancer, and exhibits rapid growth with various clinical symptoms. Physicians must appropriately manage patients with lung cancer who develop gingival metastasis. Clinical records of patients with lung cancer treated at the Department of Internal Medicine II, Okayama University Hospital, between 1976 and 1998 were retrospectively reviewed. The medical literature was searched by Medline to identify reports of gingival metastasis from lung cancer. Three of 729 (0.41%) lung cancer patients developed gingival metastasis in our hospital between 1976 and 1998, and 9 additional cases of this type of metastasis were found in the literature. All were male, and median age was 57.5 years (range, 47 to 70). There were no clear correlations between development of gingival metastasis and either histologic type or location of the primary lesion. Chemotherapy or radiotherapy was effective for treatment of gingival metastasis, and the quality of life was improved. However, survival after development of gingival metastasis was very short, with median survival of only 4 months.

Aged↗
PubMedDate not supplied

Primary signet-ring cell carcinoma of the lung with histochemical characterization.

Signet-ring cell carcinoma (SRCC) is a unique sub-type of mucin-producing adenocarcinoma characterized by abundant intracellular mucin accumulation. Although SRCC has been found in various organs, to the best of our knowledge there have only been a few reports of primary SRCC of the lung. Furthermore, most of the reports describe the coexistence of SRCC with differentiated components, while only one case has been reported as pure SRCC. We report here on a patient with primary SRCC of the lung with histochemical characterization. In our case, the tumor cells were mostly composed of signet-ring cells. Although the patient achieved only a minor response after systemic chemotherapy, he has been doing well, without any further treatment, for 33 months after diagnosis.

Carcinoma, Signet Ring Cell↗
PubMedDate not supplied

Gastric perforation due to metastasis from adenocarcinoma of the lung.

We report a rare case of the development of gastric perforation at the site of metastasis from adenocarcinoma of the lung during systemic chemotherapy. We speculated that the chemotherapy-induced necrosis of the metastatic tumor might have led to the gastric perforation. To the best of our knowledge, this is the first case of chemotherapy-induced gastric perforation as a complication of lung cancer treatment.

Adenocarcinoma↗