Biomedical subjects

Akio Yamazaki

Publications and source records attributed to Akio Yamazaki.

At least 19 recordsLinked to original sources

PubMed2006

The spread of metastatic lymph nodes to the mediastinum from left upper lobe cancer: results of superior mediastinal nodal dissection through a median sternotomy.

BACKGROUND: This study endeavored to clarify the location, frequency, and prognostic value of metastatic lymph nodes in the mediastinum among patients with left upper lung cancer who underwent complete dissection of the superior mediastinal lymph node through a median sternotomy. METHODS: Forty-four patients with left upper lobe cancer underwent extended radical mediastinal nodal dissection (ERD), all of whom were analyzed in this retrospective study. The group comprised 12 females and 32 males, with ages ranging from 28 to 70 years (median age, 60 years). Mediastinal nodal status was assessed according to the systems of Mountain/Dresler 7 and Naruke 8. The clinicopathological records of each patient were examined for prognostic factors, including age, sex, histology, tumor size, c-N number, preoperative serum CEA level, metastatic stations and distribution of metastatic nodes according to Naruke's system 8. The superior mediastinal lymph nodes which cannot be dissected through a left thoracotomy (bilateral #1 and #2, #3, right #3a, and right #4 according to Naruke's map 8 were defined as extra-superior mediastinal nodes for left lung cancer (ESMD). RESULTS: Fourteen patients had one or more metastases to mediastinal lymph nodes, among whom the most common metastatic station was the aortic nodes: 71.4% had metastasis to #5 or #6 (57.1% to #5 and 50% to #6). The next most common metastatic station was the left tracheobronchial nodes (42.8%). Metastasis to the ESMD occurred in 7 of the 44 study subjects (16%), representing a 50% rate of occurrence (7/14) among those with mediastinal nodal involvement. Univariate analysis found that CN factor and aortic nodal involvement (#5, #6) were significant predictive factors for ESMD metastasis. Multivariate analysis determined that only aortic nodal involvement was significant (p = 0.008). Furthermore, ESMD metastasis was rare (5.8%) in the absence of aortic node metastasis. The overall survival rate at 5 years was 50% among the patients without ESMD metastasis. However, the survival rate was 32% at 3 years and 0% at 5 years among the seven patients with ESMD metastasis. CONCLUSIONS: The aortic lymph node is the most common site of metastasis from left upper lobe cancer. Multivariate analysis demonstrated that aortic nodal involvement was a significant predictive factor for ESMD metastasis. Based upon the rates of metastasis and the post-operative prognosis in our study patients, dissection of aortic nodes and left tracheobronchial nodes may be important for patients with left upper lobe cancer. Whether ESMD dissection has a beneficial effect on prognosis remains controversial.

Adult↗

PubMed2006

Illuminated rhodopsin is required for strong activation of retinal guanylate cyclase by guanylate cyclase-activating proteins.

We have recently shown that activation of retinal guanylate cyclase (retGC) by GC-activating proteins (GCAPs) is much stronger than that previously reported and that preincubation of photoreceptor outer segment homogenates with ATP or its analogue, adenylyl imidodiphosphate (AMP-PNP), is required for the strong activation [Yamazaki, A., Yu, H., Yamazaki, M., Honkawa, H., Matsuura, I., Usukura, J., and Yamazaki, R. K. (2003) J. Biol. Chem. 278, 33150-33160]. Here we show that illuminated rhodopsin is essential for development of the AMP-PNP incubation effect. This was demonstrated by illumination of dark homogenates and treatments of illuminated homogenates with 11-cis-retinal and hydroxylamine prior to the AMP-PNP incubation and by measurement of the GCAP2 concentration required for 50% activation. We also found that the AMP-PNP incubation effect was not altered by addition of guanosine 5'-O-(3-thiotriphosphate), indicating that transducin activation is not required. It is concluded that illuminated rhodopsin is involved in retGC activation in two ways: to initiate the ATP incubation effect for preparation of retGC activation as shown here and to reduce the Ca2+ concentrations through cGMP phosphodiesterase activation as already known. These two signal pathways may be activated in a parallel and perhaps proportional manner and finally converge for strong activation of retGC by Ca2+-free GCAPs.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2006

Prognostic significance of metastasis to the highest mediastinal lymph node in nonsmall cell lung cancer.

BACKGROUND: We have tried to clarify the prognostic significance of metastasis to the highest mediastinal (HM) lymph node in patients with N2 lung cancer who underwent complete dissection of superior mediastinal (including HM) lymph nodes. METHODS: This study analyzed 53 patients with N2 nonsmall cell lung cancer who underwent surgical procedures such as lobectomy plus hilar and mediastinal node dissection (T4, neoadjuvant therapy cases were excluded). For patients whose cancer was in the left lung, we performed surgery through the median sternotomy in order to dissect superior mediastinal nodes. The clinicopathologic records of the patients were examined for prognostic factors such as age, sex, side, histology, tumor location, tumor size, clinical node (cN) number, preoperative serum carcinoembryonic antigen level, number of metastatic stations, and HM lymph node involvement. RESULTS: A univariate analysis showed that tumor size (T1/T2-3), cN factor (cN1-2/cN0), N2 level (multiple/single), and metastasis to the HM node were significant prognostic factors. In the multivariate analysis, metastasis to the HM lymph node remained a significant prognostic factor (p = 0.026). The 3-year survival rates were 52% in patients without metastasis to the HM lymph node and 21% in patients with metastasis to the HM lymph node (p < 0.001). Furthermore, when HM nodal involvement was absent, the 5-year survival rate was 33% even in patients with multilevel N2 status, 45% in patients with cN1-2 status, and 47% in patients with pT2-3 tumor status. CONCLUSIONS: Highest mediastinal lymph node involvement is prognostic of highly advanced N2 disease resulting in poor outcome. The results also suggest that patients with no involvement of the HM lymph node can experience acceptable postoperative outcomes even if they have multilevel N2 status, positive cN status, or T2-3 tumor status.

Adenocarcinoma↗

PubMed2006

An optimization methodology for neural network weights and architectures.

This paper introduces a methodology for neural network global optimization. The aim is the simultaneous optimization of multilayer perceptron (MLP) network weights and architectures, in order to generate topologies with few connections and high classification performance for any data sets. The approach combines the advantages of simulated annealing, tabu search and the backpropagation training algorithm in order to generate an automatic process for producing networks with high classification performance and low complexity. Experimental results obtained with four classification problems and one prediction problem has shown to be better than those obtained by the most commonly used optimization techniques.

Algorithms↗

PubMed2006

Cavernous hemangioma of the anterior mediastinum: case report and 50-year review of Japanese cases.

Hemangioma is a rare tumor of the mediastinum. We report a case of cavernous hemangioma of the anterior mediastinum that was incidentally detected by chest radiography during a routine health check. A mass lesion was seen in the anterior mediastinum on computed tomography and magnetic resonance imaging of the chest. Because a thymoma with cystic degeneration was suspected preoperatively, extended thymectomy was performed. The tumor was confined to the left lobe of the thymus without invasion into the adjacent structures. It measured 42x32x17 mm, and was completely resected without any major bleeding. Pathological examination led to the diagnosis of cavernous hemangioma. A total of 61 cases of mediastinal hemangioma, including our case, reported in Japan over the past 50 years are reviewed.

Adolescent↗

PubMed2006

A case of aspergilloma detected after surgery for pneumothorax.

We report a case of aspergilloma in an 80-year-old male patient who had no identifiable underlying disease before surgery for pneumothorax. He was hospitalized for left pneumothorax. A chest CT revealed a large bulla in the left lung apex with a nodule (diameter; 1.5 cm) at the edge of the bulla. After thoracodocesis, air leakage persisted and a large bulla and nodule were resected. Aspergillus was detected histopathologically in the nodule. Treatment with itraconazole 200 mg a day followed, and 4 months later he had no recurrent pneumothorax or Aspergillus infection.

Aged, 80 and over↗

PubMed2005

ATP binding is required for physiological activation of retinal guanylate cyclase.

ATP bound to retinal guanylate cyclase (retGC)/membranes prior to the assay (pre-binding effect) and during the assay (direct effect) further enhances retGC activity stimulated by GC-activating proteins (GCAPs). Here we investigate differences between these two effects. We found that the pre-binding effect, but not the direct effect, was absent in membranes pre-washed with Mg(2+)-free hypotonic buffers, that the pre-binding effect, but not the direct effect, was strictly limited to GCAP-stimulated retGC activity, and that these two effects were independent and additive rather than being synergistic. Pre-incubation with amiloride enhanced GCAP2-activated retGC activity in a manner similar to that by ATP pre-binding; however, amiloride did not directly stimulate the retGC activity. These results indicate that these two effects are mechanistically different. Levels of retGC activation by these effects and conditions required for these effects indicate that only the mechanism involving ATP pre-binding is physiologically relevant to retGC activation.

Adenosine Triphosphate↗

PubMed2005

Prognostic value of CD44 isoform expression in thymic epithelial neoplasms.

BACKGROUND: Many histologic classifications of thymic epithelial tumors have been reported to date, but to the authors' knowledge, none of them closely reflect the clinical behavior or prognosis of the tumor. Therefore, it is necessary to establish a biologic marker for thymic epithelial tumors. Variants of CD44 may be important in promoting tumor progression and metastasis. Accordingly, the expression of CD44 isoforms in thymic epithelial neoplasms was investigated using immunohistochemistry to assess their possible value as prognostic indicators. METHODS: Expression of CD44v6 in thymic epithelial tumors was investigated with immunohistochemistry using consecutive surgical specimens resected from 108 patients between 1983 and 2002 at Juntendo University Hospital in Tokyo, Japan. RESULTS: Among the 108 thymic epithelial tumors, 70 were negative for CD44v6, 20 were weakly positive, and 18 were strongly positive. The status of CD44v6 expression (negative vs. weakly plus strongly positive) was found to be correlated with the tumor stage according to the Masaoka staging system (noninvasive vs. invasive tumors) (P = 0.0214). When patients with tumors that were negative and weakly positive for CD44v6 expression were combined, the 5-year, 10-year, and 15-year recurrence-free survival rates were 98.2%, 95.9%, and 86.1%, respectively, whereas the corresponding rates for patients with strongly positive tumors were 73.5%, 73.5%, and 55.1%, respectively. Therefore, these two groups demonstrated a significant difference with regard to recurrence-free survival (P = 0.0172). CONCLUSIONS: CD44v6 expression in thymic epithelial neoplasms demonstrated a significant difference based on the World Health Organization classification, the Masaoka stage (invasive vs. noninvasive tumors), and recurrence, if an appropriate cutoff value was chosen in each case. This suggests that CD44v6 can be used as a marker that reflects the stage of thymic tumors.

Adult↗

PubMed2005

Multilocular thymic cyst associated with follicular hyperplasia: clinicopathologic study of 4 resected cases.

We report here 4 cases of multilocular thymic cysts (MTCs) with reactive lymphoid follicular hyperplasia. They were admitted to our hospital to examine anterior mediastinal masses demonstrated on chest computed tomographic scans. Three patients presented high-grade intermittent fever, and 2 patients were associated with Sjogren syndrome with elevated serum antinuclear antibody levels. All patients were subjected to extended thymectomy. Interestingly, their fever disappeared immediately after surgery. Histologically, the lesions were characterized by several cystic spaces separated by various thick walls with dense lymphoid tissue containing large reactive germinal centers. The inner cyst walls were lined by flattened cuboidal epithelia in some portions. Columnar epithelia with focal cilia were partially observed in 2 cases. These pathological findings led to a diagnosis of MTCs that were thought to result from cystic transformation of medullary duct derivatives by acquired inflammatory processes. The pathological findings, together with clinical courses of our cases, suggest that inflammation accompanied by autoimmune diseases may play, in part, an important role in the development of MTCs.

Adult↗

PubMed2005

Complete resection via medial sternotomy for non-small cell lung cancer in the right upper lobe.

BACKGROUND: Right upper lobectomy with right cervical and bilateral mediastinal lymph node dissection via a median approach was performed for non-small cell lung cancer. METHODS: From 1995 to 2003, 48 patients aged < or = 70 years underwent resection of cancer in the right upper lobe, including 26 with N0, four with N1 and 18 with N2 disease. RESULTS: Metastases to the right cervical, highest mediastinal, pretracheal and bilateral tracheobronchial lymph nodes were frequent. There were no operative or hospital deaths. Preoperative accuracy of N-factor diagnosis was only 35.4%. The overall 5-year survival rate was 58.8%. The rate for C-N2 disease (n = 18) was 42.6%, and the rate for p-N2 disease (n = 7) and p-N3 disease (n = 13) was 57.1% and 0%, respectively, using the Kaplan-Meier method. CONCLUSIONS: Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease.

Adenocarcinoma↗

PubMed2005

A case of diffuse pleural mesothelioma in which contralateral exploratory thoracoscopy assisted the selection of therapy.

Diffuse pleural mesothelioma is a rare condition with a poor prognosis. Recent reports have indicated that extensive surgery combined with chemotherapy and radiotherapy prolongs the survival of selected patients with early disease. Thoracoscopy allows complete visualization of the pleural cavity and provides high-quality biopsy samples. We present a case of successful diagnosis of bilateral pleural mesothelioma by thoracoscopy. It is important to observe the contralateral pleural cavity by thoracoscopy to confirm the presence or absence of a tumor before considering extrapleural pneumonectomy for mesothelioma.

Aged↗

PubMed2005

Clinical usefulness of the WHO histological classification of thymoma.

PURPOSE: Rosai et al. published the World Health Organization (WHO) classification of thymic epithelial tumors in 1999, and its clinical usefulness seems to be established. It is our purpose to find the clinically relevant diagnostic points in the WHO Histological Classification of Thymoma. METHODS: Thymomas surgically removed from 100 consecutive patients at Juntendo University Hospital between October 1983 and February 2002 were classified according to the WHO histological classification. We assessed overall survival and recurrence-free rate calculated for each tumor type in the WHO classification compared with those of tumors classified by the Masaoka system. RESULTS: The thymic epithelial tumors in this series comprised 10 type A, 15 type AB, 18 type B1, 21 type B2, 33 type B3, and 3 type C tumors according to the WHO classification. Based on the Masaoka system, the disease was stage I in 53 patients, stage II in 30, stage III in 15, and stage IV in 2. The 15-year recurrence-free rate was 100% for type A, AB and B1, while the rates for types B2 and B3 were 66.7% and 54.5%, respectively. The 10-year recurrence-free rate was 66.7% for type C. The 15-year recurrence-free rate of the 64 patients with type A, AB, B1, and B2 thymomas was significantly higher from that of the 33 patients with type B3 thymoma (p=0.0026). CONCLUSION: When using the WHO classification, it is critical to distinguish type B3 thymoma from other tumor types.

Adult↗

PubMed2005

An early case of pulmonary lymphangioleiomyomatosis diagnosed by video-assisted thoracoscopic surgery.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare and progressive disease of young women that usually causes death from respiratory failure. Here we report an early case that was diagnosed by thoracoscopy. A 28-year-old woman presented to a local clinic with chest pain and her chest X-ray film showed left pneumothorax. After placement of a chest tube, the lung re-expanded fully. Following the recurrence of left pneumothorax, she was referred to our hospital and underwent video-assisted thoracoscopic surgery (VATS). However, left pneumothorax recurred again one month later. She underwent a second thoracoscopic operation, during which a bulla was recognized in the lingular segment of the left lung and was resected. On histological examination of the surgical specimen findings consistent with LAM were obtained. Taking the preoperative imaging findings and the thoracoscopic findings into consideration, a diagnosis of early lymphangioleiomyomatosis was made. Thoracoscopic management of pneumothorax in young women can facilitate the early diagnosis of this condition.

Adult↗

PubMed2004

Enhanced induction of apoptosis in lung adenocarcinoma after preoperative chemotherapy with tegafur and uracil (UFT).

PURPOSE: To determine if the preoperative administration of tegafur and uracil (UFT) to patients with lung adenocarcinoma could induce apoptosis. METHODS: We conducted a randomized prospective study on 30 patients with lung adenocarcinoma, divided into two groups of 15 patients each. One group received UFT 600 mg/day preoperatively for 7 consecutive days and a control group received no chemotherapy or radiotherapy. The apoptotic index (AI) was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) method. Expression of Ki-67 was examined by immunohistochemical staining. The concentration of 5-fluorouracil (5-FU) in tumor tissue was measured by chemical assay. RESULTS: The AI of lung adenocarcinoma cells increased significantly in the UFT-treated group but not in the control group. A significant positive correlation was seen between the AI and the 5-FU concentrations in the tumor tissue. CONCLUSIONS: The continuous oral administration of UFT for 7 days preoperatively resulted in enhanced apoptosis and a significant positive correlation between the AI and 5-FU concentrations in lung adenocarcinoma. Therefore, it may be possible to evaluate the effects of adjuvant chemotherapy based on the AI.

Adenocarcinoma↗

PubMed2003

A critical role for ATP in the stimulation of retinal guanylyl cyclase by guanylyl cyclase-activating proteins.

It has been believed that retinal guanylyl cyclase (retGC), a key enzyme in the cGMP recovery to the dark state, is solely activated by guanylyl cyclase-activating proteins (GCAPs) in a Ca2+-sensitive manner. However, a question has arisen as to whether the observed GCAP stimulation of retGC is sufficient to account for the cGMP recovery because the stimulated activity measured in vitro is less than the light/GTP-activated cGMP phosphodiesterase activity. Here we report that the retGC activation by GCAPs is larger than previously reported and that a preincubation with adenine nucleotide is essential for the large activation. Under certain conditions, ATP is two times more effective than adenylyl imidodiphosphate (AMP-PNP), a hydrolysis-resistant ATP analog; however, this study mainly used AMP-PNP to focus on the role of adenine nucleotide binding to retGC. When photoreceptor outer segment homogenates are preincubated with AMP-PNP (EC50 = 0.65 +/- 0.20 mM), GCAP2 enhanced the retGC activity 10-13 times over the control rate. Without AMP-PNP, GCAP2 stimulated the control activity only 3-4-fold as in previous reports. The large activation is due to a GCAP2-dependent increase in Vmax without an alteration of retGC affinity for GCAP2 (EC50 = 47.9 +/- 2.7 nM). GCAP1 stimulated retGC activity in a similar fashion but with lower affinity (EC50 = 308 nM). In the AMP-PNP preincubation, low Ca2+ concentrations are not required, and retGC exists as a monomeric form. This large activation is accomplished through enhanced action of GCAPs as shown by Ca2+ inhibition of the activity (IC50 = 178 nM). We propose that retGC is activated by a two-step mechanism: a conformational change by ATP binding to its kinase homology domain under high Ca2+ concentrations that allows large enhancement of GCAP activation under low Ca2+ concentrations.

Adenine↗

PubMed2003

Fibrin glue and bioabsorbable felt patch for intraoperative intractable air leaks.

OBJECTIVE: We worked to devise a new way to prevent postoperative persistent air leaks in high-risk pulmonary surgery patients. METHODS: From November 1993 to June 2002, 60 patients with difficult to control intraoperative pulmonary air leakage were treated using bioabsorbable polyglycolide felt patches soaked in fibrin glue to cover the leakage site. RESULTS: After application, the felt patch adhered tightly to the lung surface without peeling off, enabling good leakage closure with only 2 ml of fibrin glue used. Air leakage was controlled successfully in 52 (86.7%) of the 60. Four of the 8 patients in whom this method failed to stop air leakage also developed mild pyothorax, with 2 requiring a second operation by video-assisted thoracic surgery. Leakage was eventually controlled in all patients, with no postoperative deaths relating to air leakage. CONCLUSIONS: Fibrin-glue-soaked bioabsorbable felt patches effectively seal intraoperative intractable air leaks. Felt patch use may increase the risk of postoperative infection. It should be considered for use on patients with fistulas that cannot be controlled by direct closure or otherwise intraoperatively and who may potentially develop uncontrollable air leakage postoperatively.

Absorbable Implants↗

PubMed2003

Neural network training with global optimization techniques.

This paper presents an approach of using Simulated Annealing and Tabu Search for the simultaneous optimization of neural network architectures and weights. The problem considered is the odor recognition in an artificial nose. Both methods have produced networks with high classification performance and low complexity. Generalization has been improved by using the backpropagation algorithm for fine tuning. The combination of simple and traditional search methods has shown to be very suitable for generating compact and efficient networks.

Algorithms↗

PubMed2002

Binding of cGMP to GAF domains in amphibian rod photoreceptor cGMP phosphodiesterase (PDE). Identification of GAF domains in PDE alphabeta subunits and distinct domains in the PDE gamma subunit involved in stimulation of cGMP binding to GAF domains.

Retinal cGMP phosphodiesterase (PDE6) is a key enzyme in vertebrate phototransduction. Rod PDE contains two homologous catalytic subunits (Palphabeta) and two identical regulatory subunits (Pgamma). Biochemical studies have shown that amphibian Palphabeta has high affinity, cGMP-specific, non-catalytic binding sites and that Pgamma stimulates cGMP binding to these sites. Here we show by molecular cloning that each catalytic subunit in amphibian PDE, as in its mammalian counterpart, contains two homologous tandem GAF domains in its N-terminal region. In Pgamma-depleted membrane-bound PDE (20-40% Pgamma still present), a single type of cGMP-binding site with a relatively low affinity (K(d) approximately 100 nm) was observed, and addition of Pgamma increased both the affinity for cGMP and the level of cGMP binding. We also show that mutations of amino acid residues in four different sites in Pgamma reduced its ability to stimulate cGMP binding. Among these, the site involved in Pgamma phosphorylation by Cdk5 (positions 20-23) had the largest effect on cGMP binding. However, except for the C terminus, these sites were not involved in Pgamma inhibition of the cGMP hydrolytic activity of Palphabeta. In addition, the Pgamma concentration required for 50% stimulation of cGMP binding was much greater than that required for 50% inhibition of cGMP hydrolysis. These results suggest that the Palphabeta heterodimer contains two spatially and functionally distinct types of Pgamma-binding sites: one for inhibition of cGMP hydrolytic activity and the second for activation of cGMP binding to GAF domains. We propose a model for the Palphabeta-Pgamma interaction in which Pgamma, by binding to one of the two sites in Palphabeta, may preferentially act either as an inhibitor of catalytic activity or as an activator of cGMP binding to GAF domains in frog PDE.

Amino Acid Sequence↗