Biomedical subjects

Akinori Iwasaki

Publications and source records attributed to Akinori Iwasaki.

At least 19 recordsLinked to original sources

PubMed2006

Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung.

OBJECTIVE: To analyze the prognostic value of hypoxia-inducible factor-1 (HIF-1) alpha expression and its correlation with clinicopathologic variables and the expression of vascular endothelial growth factor-A and -C in patients with lung adenocarcinomas of small size. METHODS: The expression of hypoxia-inducible factor-1 alpha was immunohistochemically determined in 78 cases of small-sized adenocarcinoma (maximum dimension < or = 2 cm) using antibody against a recombinant protein corresponding to amino acids 575-780 of hypoxia-inducible factor-1 alpha. Data regarding patient survival, clinicopathologic factors, and immunohistochemical studies of vascular endothelial growth factors were also collected. RESULTS: Strong expression of hypoxia-inducible factor-1 alpha was observed in 23 of 78 cases; absent or minimal expression was found in the localized bronchioloalveolar carcinomas. Strong expression of hypoxia-inducible factor-1 alpha was significantly higher in cases with vascular invasion, lymph node involvement, and vascular endothelial growth factor-A expression. The 5-year survival rate was 63.2% if expression of hypoxia-inducible factor-1 alpha was strong and 85.1% if expression was weak (p < 0.05). CONCLUSION: Immunohistochemical staining of HIF-1 alpha, along with examination of metastatic potential via vascular pathways, may be valid defining a subpopulation of patients with small-sized adenocarcinoma of the lung whose tumors have aggressive angiogenesis potential.

Adenocarcinoma↗

PubMed2006

In vivo EPR dosimetry to quantify exposures to clinically significant doses of ionising radiation.

As a result of terrorism, accident or war, populations potentially can be exposed to doses of ionising radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk can have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. It is extremely unlikely that adequate dosemeters will be worn by the potential victims, and it also will be unlikely that prompt and accurate dose reconstruction at the level of individuals will be possible. Therefore, there is a critical need for a method to measure the dose from radiation-induced effects that occur within the individual. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently to classify individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosemeter can provide estimates of absorbed dose of +/- 0.5 Gy in the range from 1 to >10 Gy. The lower limit and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. In its current state of development, the method is already sufficient for decision-making action for individuals with regard to acute effects from exposure to ionising radiation for most applications related to terrorism, accidents or nuclear warfare.

Body Burden↗

PubMed2006

A novel method for preserving human lungs using a super-cooling system.

PURPOSE: To ensure the suitable preservation of isolated lungs, a super-cooling system was used to cool water to temperatures as low as -5 degrees C without freezing. DESCRIPTION: After lung tissues were obtained from patients with lung cancer, they were kept at -5 degrees C or 4 degrees C for as many as 5 days, and then they were histologically and biochemically examined. To evaluate biochemical stability, tissues after storage were passively sensitized with immunoglobulin E and then incubated with anti-immunoglobulin-E antibody. EVALUATION: Although tissues preserved at -5 degrees C for 5 days had an almost normal appearance with intact cilia on bronchial epithelium and normal endothelium, tissues stored at 4 degrees C showed degradation of these structures. Single-stranded DNA, a sign of DNA cleavage, was frequently noted in tissues stored at 4 degrees C, but only rarely observed at -5 degrees C. A significant amount of cysteinyl-leukotrienes was generated from tissues stored at -5 degrees C for 3 days, but there was no response to antibody stimulation from tissues stored at 4 degrees C. CONCLUSIONS: Super-cooling systems may provide useful applications as a novel preserving method.

Aged↗

PubMed2006

Video-assisted thoracoscopic surgery lobectomy for c-T1N0M0 primary lung cancer: its impact on locoregional control.

BACKGROUND: The outcomes of a video-assisted thoracoscopic surgery lobectomy for lung cancer, with a special focus on its locoregional control, were compared with a conventional lobectomy. METHODS: We performed a retrospective review of 160 patients who had undergone a lobectomy either by means of thoracoscopic surgery (n = 81) or a standard thoracotomy (n = 79) for clinical T1N0M0 nonsmall-cell lung cancer. The overall, disease-free, and locoregional recurrence-free survival were compared. In a separate multivariate analysis, the ability of numerous clinical and surgical factors, including the surgical approach, to predict locoregional recurrence was investigated. RESULTS: The total recurrence of the primary disease occurred in 28 cases (12 locoregional and 14 distant). In the 12 documented local recurrences, 8 belonged to the thoracoscopic surgery group and 4 were in the standard thoracotomy group, without significant differences (p = 0.229). The overall 5-year survival rates associated with the thoracoscopic and standard procedure were 89.1% and 77.7%, respectively (p = 0.149). No significant differences in the disease-free or locoregional recurrence-free survivals were observed between the groups. The results of a multivariate analysis for the incidence of total and locoregional recurrence demonstrated that two covariates, lymph node metastasis and the surgical side (right or left lung), were significant factors for both total and locoregional recurrence. No significant relationship was found between thoracoscopic surgery or standard thoracotomy, and the incidence of locoregional recurrence. CONCLUSIONS: Our findings suggest that thoracoscopic surgery is not inferior regarding its ability to achieve locoregional control in comparison with the standard procedure.

Aged↗

PubMed2006

Lung cancer surgery in patients with liver cirrhosis.

BACKGROUND: Few reports have described surgery for lung cancer in patients with liver cirrhosis. The objective of this study was to clarify the efficacy of surgical treatment and evaluate its postoperative outcome. METHODS: We retrospectively reviewed the medical charts of 17 patients between 1985 and 2005 who were found to have nonsmall cell lung cancer (NSCLC) with liver cirrhosis. The grading of the severity of liver cirrhosis was made according to the Child-Pugh classification. RESULTS: Four patients were classified as Child-Pugh class A, whereas another 13 patients were classified as Child-Pugh class B. Of these 17 patients, 11 underwent lobectomies, 3 underwent pneumonectomies, and 3 underwent wedge resections. The only patient who experienced hospital death (5.9%) was a male patient with Child-Pugh class B cirrhosis. There were five respiratory-associated postoperative complications including pneumonia, bleeding from the staple line, and prolonged air leak. The morbidity rate was 29.5%. Median duration of chest tube insertion was 6.8 days, and mean volume of pleural effusion was 1,015.0 mL at 3 days total postoperatively. A total of 9 deaths occurred during follow-up (3 from cancer, 4 from hepatic failure, 1 from cardiac causes, and 1 unknown). The overall survival was 87.8%, 57.0%, and 45.6% at 1, 3, and 5 years, respectively. None of the patients experienced morbidity or mortality in Child-Pugh class A, but class B had 30.8% morbidity and 7.6% mortality. CONCLUSIONS: Surgical treatment may be an acceptable and valuable approach for NSCLC patients who also have low severity liver cirrhosis.

Adenocarcinoma↗

PubMed2006

Human pulmonary dirofilariasis: a case report and review of the recent Japanese literature.

Human pulmonary dirofilariasis is a rare zoonotic infection caused by the dog heartworm Dirofilaria immitis, which is transmitted via a vector/intermediate host, generally the mosquito. The authors present a case of histologically diagnosed human pulmonary dirofilariasis, in which the lesion was resected using video-assisted thoracic surgery (VATS). The authors also review 24 cases of such zoonosis reported in Japan from 1998 to 2004. Of these 24 patients with human pulmonary dirofilariasis, 12 (50%) were men (mean age 54 years, range 29-80 years) and 67% were asymptomatic. Most patients (83%) had a solitary lung nodule, 95% of the lesions were <30 mm and 13% had a pleural effusion. VATS was performed to obtain a histopathological diagnosis in the majority (61%) of patients whom the authors reviewed. VATS would appear to be the best method for diagnosing pulmonary dirofilariasis.

Aged↗

PubMed2006

[Pleomorphic carcinoma of the lung with high serum granulocyte colony stimulating factor, suggested of pulmonary abscess by preoperative radiology; report of a case].

A 52-year-old man with a history of heavy smoking was hospitalized for evaluation of fever. Pulmonary abscess was initially suspected by computed tomography (CT) showing an ovoid, well-demarcated nodule of 61 mm in diameter with coarse calcification in S2a of the right lung. The patient was treated with antibiotics, but no improvement was seen in inflammatory reactions or lesion size. Marked leukocytosis and high level of granulocyte colony stimulating factor (G-CSF) was shown by laboratory examination. To improve patient condition and ensure correct diagnosis, right upper lobectomy of the lung was performed. Pleomorphic carcinoma of the lung was subsequently diagnosed. G-CSF producing tumor was suspected, since the normalization of serum G-CSF level followed by the improvement of both fever and inflammatory reaction was observed postoperatively. We also present herein a review of 22 Japanese cases of pleomorphic carcinoma producing G-CSF of the lung, characterized by leukocytosis.

Carcinoma↗

PubMed2005

Identification of a ring chromosome with spectral karyotyping in a pleural synovial sarcoma.

The origin of a ring chromosome in a monophasic synovial sarcoma of the diaphragmatic pleura of an 18-year-old man was investigated using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis revealed the following clonal karyotypic abnormalities: 47,Y,t(X;18)(p11.2;q11.2),t(11;19)(q12;q13.4),+12,-13,+r[6]. The SYT-SSX1 fusion transcript was detected with reverse transcriptase-polymerase chain reaction analysis. SKY analysis suggested that the ring chromosome was composed of material from chromosome 8. Subsequent FISH analysis with a whole-chromosome 8 paint probe confirmed the SKY results. This study demonstrates the usefulness of SKY as an adjunct for determining the chromosomal composition of ring chromosomes.

Adolescent↗

PubMed2005

Inflammatory myofibroblastic tumor of the posterior mediastinum: an older adult case with anaplastic lymphoma kinase abnormalities determined using immunohistochemistry and fluorescence in situ hybridization.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that usually occurs in children and young adults. Anaplastic lymphoma kinase (ALK) abnormalities in IMT, determined using immunohistochemistry and/or molecular genetic studies, including fluorescence in situ hybridization (FISH), have almost been limited to children and young adults. In elderly cases of IMT, these ALK abnormalities are very rare. We report on a case of IMT arising in the posterior mediastinum of a 59-year-old Japanese man that showed ALK abnormalities determined using immunohistochemistry and FISH, suggesting the neoplastic nature of a subset of IMTs in older patients similar to those in younger ones and the presence of an additional mechanism(s) that allows them to start to grow late.

Anaplastic Lymphoma Kinase↗

PubMed2005

Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ.

There are plausible circumstances in which populations potentially have been exposed to doses of ionizing radiation that could cause direct clinical effects within days or weeks, but there is no clear knowledge as to the magnitude of the exposure to individuals. In vivo EPR is a method, perhaps the only such method that can differentiate among doses sufficiently to classify individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. Individuals with significant risk then can have appropriate procedures initiated immediately, while those without a significant probability of acute effects could be reassured and removed from the need for further medical treatment. In its current state, the in vivo EPR dosimeter can provide estimates of absorbed dose of +/-25 cGy in the range of 100-->1000 cGy. This is expected to improve, with improvements in the resonator, the algorithm for calculating dose, and the uniformity of the magnetic field. In its current state of development, it probably is sufficient for most applications related to terrorism or nuclear warfare, for decision-making for action for individuals in regard to acute effects from exposure to ionizing radiation.

Algorithms↗

PubMed2005

Differentiation of the observed low frequency (1200MHz) EPR signals in whole human teeth.

We have determined the properties of the various signals that are observed in vivo so this information can be used to develop procedures for data acquisition and data analysis that will enable the accurate determination of radiation-induced dose with a resolution of 50cGy. Using the 1200MHz in vivo EPR spectrometer and isolated human teeth, we found four types of signals whose properties overlap, but also have some distinct properties that can be exploited to resolve them. The intrinsic background signal in human teeth differs modestly from the radiation-induced signal in g-factor, shape, and power saturation. Random noise from instrumental conditions can be reduced with signal averaging. The microphonic signal varies with the particular experimental setup and has some properties similar to real EPR signals, but is constant if the conditions are not changed. It can be suppressed by improvements in hardware and software, or subtracted.

Algorithms↗

PubMed2005

In vivo measurements of EPR signals in whole human teeth.

Low-frequency EPR has the potential advantage of making accurate and sensitive measurements of absorbed radiation dose in teeth in situ. We report here on measurements within the human mouth in volunteers using 1200 MHz EPR, with an irradiated tooth in a special holder. We obtained a signal/noise ratio within 50% of that seen when the same sample was measured extraorally. The intraoral signal/noise can be improved and can be reduced further with optimization of conditions and use of more specifically designed and optimized resonators that fit within the mouth, probing 1-4 teeth, and can make the measurements in molars or incisors. The presence of amalgam fillings did not significantly impact the accuracy of measurements in those teeth or in adjacent teeth. These initial results make us optimistic that intra-oral measurements of the teeth will be feasible for accurate determination of exposures over the whole range in which acute clinical effects are possible.

Body Burden↗

PubMed2005

Clinical evaluation of systemic inflammatory response syndrome (SIRS) in advanced lung cancer (T3 and T4) with surgical resection.

OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is well known to occur in patients who have suffered organ damage or trauma, or undergone surgery. SIRS provides useful information in patients with morbidity after surgery. To date, there has been no report of SIRS after surgery in patients with lung cancer. Therefore, based on this new concept of the syndrome, we review here a series of T3 and T4 NSCLC patients who underwent extended resection at our hospital, and attempt to identify the value and correlation of SIRS in predicting the morbidity of such patients. METHODS: We retrospectively reviewed the patients with NSCLC treated at our hospital between January 1994 and August 2003. Among these 720 patients, a curative approach was attempted in 144 with advanced stage (T3, 100; T4, 44) cancer. The patients were consequently divided into three groups (G1, negative or less than 3 days in SIRS following surgery; G2, less than 7 days; G3, continued over 7 days). Pre- or peri-operative factors were evaluated, and the 5-year survival rates were analyzed. Post-operative morbidity was also compared between the three groups in association with SIRS. RESULTS: Pre-operative counts of WBC were 8848.28+/-3879.21/microl in G3 compared with 7383.33+/-3132.98/microl in G2 and 6778.31+/-3184.89/microl in G1. Values in G3 were significantly higher than those in the other groups (P<0.001). Predicted %FEV1 in G3 was significantly lower than those in the other groups. Duration of SIRS after lung surgery was associated with high levels in WBC and low %FEV1. Post-operative morbidity such as bronchial fistula or ARDS were more frequent in the G3 and G2 groups than in G1. The 1-year survival was as follows; G1, 75.4%; G2, 47.9%; G3, 38.1%. Overall 5-year survival rate for NSCLC with T3 and T4 was 32.2%, and the difference between G3 and the other groups in terms of survival was statistically significant (P<0.0001). CONCLUSIONS: The concept of SIRS have been associated with post-operative complications and survival in NSCLC. Surgical candidates should be carefully according to the predicting factor of SIRS.

Adenocarcinoma↗

PubMed2005

Prevention of acute lung allograft rejection in rat by the janus kinase 3 inhibitor, tyrphostin AG490.

BACKGROUND: Tyrphostin AG490 (AG490) potently and selectively inhibits gammac/Janus kinase 3-dependent signaling pathways, including downstream Stat5a/b activation and subsequent T cell proliferation by alloantigen stimulation. We evaluated the effects of AG490 on acute rat lung allograft rejection. METHODS: A 7-day course of an intraperitoneal (IP) injection with 10 mg/kg, 15 mg/kg, or 20 mg/kg AG490 was administered to inhibit the rejection of orthotopically transplanted Brown Norway (RT1n) rat lung allografts in Fischer 344 (RT1(1vl)) rat recipients. The progression of allograft rejection was evaluated by X-ray with a semi-quantitative scoring system and was evaluated histologically with a semi-quantitative rejection scoring system for acute lung allograft rejection. Moreover, to determine whether AG490 regulates CD4+ T cell differentiation during acute rejection, flow cytometry was used to investigate Th1 (interferon-gamma) and Th2 (interleukin [IL]-4, IL-10) intracellular cytokine profiles and the CD4+CD25+ T cell population in recipient splenocytes. RESULTS: Results of radiology and histology confirmed that treatment with AG490 significantly suppressed acute lung allograft rejection. Furthermore, the splenocytes of the AG490-treated recipients had significantly lower production of interferon-gamma and relatively higher production of IL-10, implying that a Th2 shift was induced by AG490. In addition, AG490-treated recipients had a significantly increased population of CD4+CD25+ T cells in their splenocytes on Day 6 after transplantation. CONCLUSION: These findings suggest that treatment with AG490 prevents acute lung allograft rejection in rats. The effects of AG490 may contribute to development of CD4+CD25+ T cells and a Th2 shift of CD4+ T cells.

Acute Disease↗

PubMed2005

Contribution of anaphylatoxins to allergic inflammation in human lungs.

The contribution of complement activation to allergic asthma remains controversial. In order to elucidate the role played by the complement split products, anaphylatoxins C3a and C5a, we evaluated their effects on production of cysteinyl-leukotrienes (cysLTs) by human lung fragments following an anaphylactic reaction. The lung tissues obtained from two patients with lung cancer showed C5aR-, C5L2R-, and C3aR-mRNA expression. When the chopped lung fragments passively sensitized with human IgE were incubated with anti-human IgE antibody, a significant amount of cysLTs was generated in comparison with the control (without anti-IgE antibody). The co-addition of human C5a at doses of 0.1 to 10 ng/ml to the anti-IgE antibody potentiated cysLT production. The response was bell-shaped in distribution, significant, and peaked at a C5a concentration of 1 ng/ml. The co-addition of human C3a up to 1,000 ng/ml seemed to increase cysLT production, but not to any significant extent. A novel C5a receptor complementary peptide, acetylated peptide A, dose-dependently inhibited cysLT production by the human lung fragments following the anaphylactic reaction in the presence of 1 ng/ml C5a. However, this peptide did not inhibit cysLT production in the presence of 100 ng/ml C3a. It is suggested that the anaphylatoxin C5a potentiates cysLT production in human lung tissues and contributes to allergic inflammation in disorders such as asthma, thus acetylated peptide A may be useful for suppressing allergic inflammation in the lungs.

Anaphylatoxins↗

PubMed2005

Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern.

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E-cadherin-mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E-cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non-micropapillary, area. The adhesive function of E-cadherin depends on the integrity of the entire cadherin-catenin-actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.

Adenocarcinoma↗

PubMed2005

[Review and evaluation of limited resection for early lung cancer].

Limited resection for early lung cancer has been associated with significantly higher local recurrence rates based on previous reports such as those from lung cancer study groups. On the other hand, a few groups demonstrated that patients with small peripheral cancer who undergo limited resection have comparable survival rates with those who undergo lobectomy. Recent advances in radiologic investigation and pathologic analysis have broadened the indications for limited resection. Since the introduction of the adenocarcinoma classification by Noguchi surgery for localized bronchioloalveolar carcinoma has focused on limited resection. Caution is necessary when performing wedge resection even if 10 mm or less in diameter and in compromised segmentectomy for early lung cancer. Although limited resection is still controversial intentional segmentectomy for localized bronchioloalveolar carcinoma or less than 20 mm or less in diameter may be recommended without evidence-based medicine. It is important to accumulate further evidence clarifying the survival and function benefits of limited resection. New therapeutic modalities for limited surgery for small-sized lung cancer may increase patient life expectancy.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2004

Clinical applications of EPR: overview and perspectives.

The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.

Animals↗