Biomedical subjects

Mari Fukunaga

Publications and source records attributed to Mari Fukunaga.

16 recordsLinked to original sources

PubMed2005

Cilostazol attenuates gray and white matter damage in a rodent model of focal cerebral ischemia.

BACKGROUND AND PURPOSE: To evaluate whether delayed treatment with the antiplatelet agent cilostazol reduces the volume of infarction in the gray and white matter in a rodent model of permanent focal cerebral ischemia and to explore the mechanism of the neuroprotective effect in vivo. METHODS: Cilostazol (30 or 50 mg/kg) or vehicle was administered by gavage 30 minutes and 4 hours after the induction of cerebral ischemia by permanent occlusion of the left middle cerebral artery (MCA). Animals were euthanized 24 hours after MCA occlusion, and the volume of gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein immunohistochemistry. Dynamic susceptibility contrast MRI was used to assess regional cerebral blood volume (CBV) and cerebral blood flow (CBF). RESULTS: Treatment with the higher dose of cilostazol (50 mg/kg) significantly reduced the volume of gray matter damage and axonal damage in the cerebral hemisphere by 45.0% (P<0.02) and 42.4% (P<0.002), respectively, compared with the control group. Relative CBV in the peri-infarct area after MCA occlusion was significantly increased in the cilostazol-treated group (50 mg/kg) compared with the control group (P<0.05). Relative CBF tended to be higher in the cilostazol-treated group compared with the control group. CONCLUSIONS: Treatment with cilostazol significantly reduced the gray and white matter damage associated with permanent focal ischemia. Cilostazol improved CBV and CBF in the peri-infarct area. The major action of cilostazol is to increase perfusion in the ischemic penumbra.

Animals↗

PubMed2004

Amyloid tumor in the anterior mediastinum: report of a case.

A 33-year-old woman being treated for rheumatoid arthritis was referred to our hospital for investigation of a mediastinal mass. A chest computed tomography scan showed an anterior mediastinal mass, 8.5 x 7.0 cm in size, with a cystic lesion and calcification. These findings were suggestive of either a noninvasive thymoma or a mature teratoma. Therefore, we performed tumor resection and thymectomy. Histologically, the tumor consisted of diffuse deposits of massive eosinophilic amorphous material. The tumor was stained red-orange by Congo red, and the staining disappeared following potassium permanganate digestion. Based on these findings, a diagnosis of reactive amyloidosis of the amyloid A-protein-derived type was made. Amyloidosis in the mediastinum has rarely been described.

Adult↗

PubMed2004

Incidental partial anomalous pulmonary venous connection in left lung cancer.

We present the case of a 79-year-old woman with partial anomalous pulmonary venous connection (PAPVC), discovered incidentally during upper left division segmentectomy for primary lung cancer. The left superior pulmonary vein originated from the hilum of the upper left lobe and flowed into the left brachiocephalic vein. The left inferior pulmonary vein was connected normally, and neither atrial septal defect nor other anomalous condition was present. Upper left lobectomy with ligation of the anomalous connected vein was performed, as the lingual segment was anatomically difficult to retain. Although this type of PAPVC is extremely rare, it is advisable to exercise caution when performing lung resection with the potential for PAPVC in mind.

Aged↗

PubMed2004

Fixation of silicone stents in the subglottic trachea: preventing stent migration using a fixation apparatus.

Silicone stents are widely used to treat benign or malignant airway stenosis. However, since straight silicone stents placed into the subglottic trachea to treat stenosis display a high risk of migration, novel approaches are required. The present report outlines our method of external fixation for silicone stents in the subglottic trachea. This technique utilizes a fixation apparatus, is readily performed, and may help to overcome the hesitation seen in placing silicone stents for subglottic tracheal stenosis.

Bronchoscopy↗

PubMed2004

Continuous muscle stretch prevents disuse muscle atrophy and deterioration of its oxidative capacity in rat tail-suspension models.

OBJECTIVE: The purpose of this study was to evaluate the effect of continuous muscle stretch on disuse-atrophied muscles. DESIGN: Sprague-Dawley rats were used and divided into five groups: control group, hind limb suspended for 3 and 7 days, and hind-limb suspension plus strenuous continuous muscle stretch for 3 and 7 days. In the hind-limb suspension plus strenuous continuous muscle stretch groups, the gastrocnemius-plantaris-soleus muscles were stretched using a plastic plate that immobilized the ankle joint at the maximum dorsal flexed position during the hind-limb suspension period. The intracellular energy metabolism of the working muscle during electric stimulation was evaluated by phosphorus-31 magnetic resonance spectroscopy in vivo. Changes in phosphocreatine, inorganic phosphate, and the intracellular pH were monitored to evaluate intramuscular oxidative capacity. Maximum tension and muscle wet mass were also measured. RESULTS: The oxidative capacity, muscle wet weight, and maximum tension decreased after hind-limb suspension. The muscle oxidative capacity at control levels was maintained during the first 3 days in muscles subjected to continuous strenuous stretch. It was also effective to prevent the decrease in muscle mass and maximum twitch tension during the initial 3 days. However, the effects did not persist. CONCLUSION: Continuous strenuous stretch was effective to prevent disuse muscle atrophy and its functional deterioration; however, its effects did not last long.

Animals↗

PubMed2004

Gene therapy eradicating distant disseminated micro-metastases by optimal cytokine expression in the primary lesion only: novel concepts for successful cytokine gene therapy.

The most serious problem in current gene therapy is that clinical applications have often led to unsatisfactory results. Here we show novel concepts and crucial factors that have been missing for successful cytokine gene therapy. A clinically-relevant mouse model of primary and micro-metastatic osteosarcoma was generated by subcutaneously and intravenously injecting murine osteosarcoma LM8 cells, in which adenoviral gene transduction efficiencies were extremely low; current therapies remain less effective for such disseminated micro-metastases. A single injection of adenoviral vector encoding interleukin-2 gene (Ad.IL-2) was given only into the established primary tumor. Notably, antitumoral immunity was successfully elicited by IL-2 secretion from connective tissues adjacent to the primary tumor, and this immunity not only suppressed primary tumor growth but also eradicated disseminated micro-metastases in distant organs. Most importantly, not only minimal side effects but also maximal therapeutic effects were exerted only in the case of injecting the optimal (i.e., not the highest) dose of Ad.IL-2, because spleen injuries caused by excessive levels of circulating IL-2 might diminish the therapeutic effect. Although the narrow range of the optimal therapeutic expression level of IL-2 may be crucial, it was feasibly determined by serum IL-2 levels. Thus, a crucial factor for successful cytokine gene therapy is not the high gene transduction efficiency in the tumor, which has been generally recommended, but the use of the optimal therapeutic expression level. In conclusion, just a single injection of Ad.IL-2 into a primary tumor lesion, which is feasible, not invasive and cost effective, is potently therapeutic for distant disseminated micro-metastases, as long as the optimal therapeutic level is monitored. These novel concepts, which contradict those of previous studies, warn researches about the possible problems with the ongoing clinical cytokine gene therapy.

Adenoviridae↗

PubMed2003

Cilostazol reduces brain lesion induced by focal cerebral ischemia in rats--an MRI study.

To investigate the effects of cilostazol on the hemispheric ischemic lesion, we monitored the apparent diffusion coefficient (ADC) and T2 images by MRI techniques in comparison with histology at the terminal of and after 24-h reperfusion following 2-h occlusion of middle cerebral artery (MCA). The ADC values of tissue water and T2-weighted images were quantified by high field magnetic resonance. No significant difference was observed by ADC image among vehicle and cilostazol treatment groups when measured during MCA occlusion. Oral treatment with cilostazol 30 mg/kg two times at 5 min and 4 h significantly suppressed the hemispheric lesion area and volumes when detected by ADC, T2 images and histology, but 3 and 10 mg/kg cilostazol were without effect. Cilostazol (30 mg/kg) significantly reduced the increased cerebral water content at the ischemic hemisphere compared with vehicle group. In line with these results, the neurological deteriorations were much improved in the cilostazol-treated group. Taken together, it is concluded that post-treatment with cilostazol exerts a potent protective effect against cerebral infarct size by reducing the cytotoxic edema.

Animals↗

PubMed2003

An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice.

The most serious problem in current gene therapy is discrepancies between experimental data and actual clinical outcomes, which may be due to insufficient analyses and/or inappropriate animal models. We have explored suicide gene therapy by using various clinically relevant animal models and doubt the clinical use of maximal suicide gene expression, which has been generally recommended. To explore this subject further, we studied what expression level of suicide gene and what promoter led to the maximal clinical benefit in the case of hepatic metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral vectors that express herpes simplex virus thymidine kinase (HSV-tk) under different promoters were scrupulously investigated in 2 mouse models of hepatic metastasis of gastric cancer that possess clinical characteristics. Surprisingly, increases in HSV-tk expression beyond a certain point, achieved by the Rous sarcoma virus long terminal repeat promoter, not only enhanced the adverse side effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but also failed to further increase therapeutic potential. Moreover, the carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential of which had been underestimated, was much more useful-even in the case of low CEA-producing cancer-than had been previously reported. In conclusion, the optimal therapeutic expression level of a suicide gene is a novel concept and a crucial factor for successful cancer gene therapy. The present results, which contradict those of previous studies, alert researchers about possible problems with ongoing and future clinical trials that lack this concept.

Adenoviridae↗

PubMed2003

Resection of synchronous lung and Vater's papilla cancer.

We present a case of a 78-year-old man with a synchronous double cancer of the lung and Vater's papilla. A pancreaticoduodenectomy was performed for Vater's papilla cancer and a partial lung resection for lung cancer. The pathological diagnosis of the tumors was a well differentiated tubular adenocarcinoma and well differentiated bronchioloalveolar carcinoma, respectively. Although most cases of synchronous double cancers involve lung and gastric cancers, a combination of lung and Vater's papilla is extremely rare. This patient is still alive with no recurrence for 5 years after the last operation.

Adenocarcinoma↗

PubMed2003

Rapid-growth lung cancer associated with a pulmonary giant bulla: a case report.

A giant bulla of the lung is suggested as a risk factor for lung cancer. Here we report a case with lung cancer in a giant bulla, which showed rapid progression. A 57-year-old man, who had a history of heavy smoking, was admitted to our hospital due to hemoptysis. A chest X-ray revealed a giant bulla with a ground glass shadow and a high fluid level in the right upper lung. Sputum cytology was negative for malignant cells. A chest X-ray a month later showed increases of the size of the radio-opaque shadow and of the air-fluid retention, suggesting pulmonary hemorrhage from the giant bulla. Limited resection or lobectomy was indicated, but pneumonectomy was performed due to the severe air-leak. Macroscopically, a multiple nodular tumor arose from the bulla wall, which might be related to blood flow and necrotic tissue. The postoperative pathological diagnosis was papillary adenocarcinoma. Unfortunately, the patient developed a recurrence of carcinoma in the pleuroperitoneal cavity and died at 2.5 months after the operation. Based on this report and review of other cases in the literature, we should keep in mind the rapid progression of lung cancer in association with an emphysematous bulla.

Adenocarcinoma, Papillary↗

PubMed2003

Electrical stimulation prevents deterioration of the oxidative capacity of disuse-atrophied muscles in rats.

INTRODUCTION: The purpose of this study was to evaluate the effects of electrical stimulation on disuse-atrophied muscles. METHODS: Sprague-Dawley rats were used and divided into three groups: control (C), hind-limb suspended for 7 d (HS), and HS plus transcutaneous electrical stimulation for 7 d (ES). In the ES group, transcutaneous electrical stimulation was induced at 1 Hz for 1 h every day to condition the gastrocnemius-plantaris-soleus muscles. Muscle oxidative capacity was evaluated by 31P-MRS in vivo. Maximum tension and muscle wet mass were also measured. RESULTS: Muscle oxidative capacity decreased within 1 wk in HS; however, it was maintained when electric stimulation was applied to the suspended limb. The maximum twitch tension in HS was significantly smaller than that in C (p < 0.05), while in ES it did not differ from that in C. The muscle mass was significantly smaller in the HS and ES groups compared to C (p < 0.05). CONCLUSION: These data indicated that twitch electrical stimulation was effective in preventing deterioration of muscle functions, such as maximum tension and oxidative capacity, induced by 1 wk of disuse.

Animals↗

PubMed2002

Outcome for malignant tracheobronchial stenoses in esophageal cancer.

OBJECTIVE: Optimal tracheobronchial stenosis treatment in esophageal cancer remains a clinical challenge. METHODS: Subjects were 26 patients with tracheobronchial stenosis due to esophageal cancer treated by modalities such as expandable metallic stent emplacement, laser therapy, radiotherapy, and/or chemotherapy. We assessed patient outcome and modality efficacy, and determined prognostic factors for survival using multivariate analysis. RESULTS: Of the 26, 16 (61%) had improved respiration after treatment. Average posttreatment survival was 140 days (10-1550 days). Multivariate analysis indicated that a Karnofsky performance score of > or = 70% was the most significant prognostic factor, with chemotherapy and laser therapy also significant factors. CONCLUSIONS: Although individual modalities were effective in ameliorating respiratory symptoms, patients with good performance status survived the longest. After a tracheobronchial stenosis diagnosis in esophageal cancer patients, chemotherapy and laser therapy are recommended if the patient is in good general condition.

Aged↗

PubMed2002

Vasoactive peptides in a pulmonary embolism model.

PURPOSE: To investigate changes in atrial natriuretic peptide (ANP) and angiotensin II (AT-II) levels in a canine model of pulmonary embolism (PE), created by embolizing the left posterior pulmonary artery with gelatin powder. METHODS: Pulmonary arterial pressure (PAP) was measured before, immediately after, and 1 day after pulmonary artery embolization. Plasma ANP and AT-II levels were measured by radioimmunoassay (RIA) before and 1, 3, 7, 14, 21, and 28 days after embolization. ANP and AT-II levels were also measured by RIA in both embolized and nonembolized lung tissue 28 days after embolization. RESULTS: No changes in plasma ANP or AT-II were seen within 28 days after embolization. Although the ANP level in the nonembolized lung tissue was significantly increased, the level in the embolized lung tissue was significantly decreased compared with that of sham-operated control lung tissue. The AT-II level in the nonembolized lung tissue was significantly decreased compared with that of the control lung tissue, but the level in the embolized lung tissue did not change. CONCLUSION: Both ANP and AT-II in the nonembolized lung tissue reacted to compensate for vasoconstriction caused by the PE in this model.

Angiotensin II↗

PubMed2002

Adenoviral herpes simplex virus thymidine kinase gene therapy in an orthotopic lung cancer model.

BACKGROUND: Although adenovirus-mediated herpes simplex virus thymidine kinase (HSVtk) gene therapy is a potential candidate for a novel effective therapy for lung cancer, previous studies have been performed only in a subcutaneous tumor model employing nude mice. We studied therapeutic potentials in correlation with accurate adenoviral gene transduction efficiency in a more clinically relevant orthotopic lung cancer model employing immunocompetent mice. METHODS: To analyze the cytotoxicity of adenoviral HSVtk gene transduction and ganciclovir, a cell proliferation assay was performed in vitro. A survival study was carried out in immunocompetent mice with orthotopic lung cancer, which was generated by intrapulmonary inoculation with syngeneic murine lung cancer cells that had been infected beforehand with each adenoviral vector at the predetermined gene transduction efficiencies. RESULTS: Tumor cells were efficiently killed by infection with adenovirus carrying the HSVtk gene with the addition of ganciclovir in vitro. In the in vivo experiment all control mice died of rapid growth of the primary lung cancer and of metastases to mediastinal lymph nodes within 26 days after tumor inoculation. In contrast 50% and 100% of mice survived more than 40 days after inoculation with adenovirally HSVtk-transfected tumor cells that moderately and highly expressed HSVtk, respectively, when followed by ganciclovir administration. Gene transduction efficiencies were 67%. CONCLUSIONS: Adenovirus-mediated HSVtk gene therapy may be therapeutic for lung cancer when gene transduction efficiencies and sufficient expression levels of HSVtk can be achieved. Moreover, the present findings underscore the importance of the mouse orthotopic lung cancer model for studies of gene therapy.

Adenocarcinoma↗

PubMed2002

Minute lung carcinoma associated with focal honeycombed lesion.

We report a case of minute lung carcinoma that developed in a focal honeycombed lesion in the right lung. A 70-year-old man presented hemosputum, and a cytological examination result was at class IV. A right lower lobectomy of the lung was performed. Microscopically, the thickened alveolar wall revealed tumor cells indicating a minute carcinoma, and showed squamous hyperplasia, metaplasia, and dysplasia, with the carcinoma in the distal airway epithelium. This peripheral lung carcinoma in a focal honeycombed lesion demonstrated the various stages of multistep carcinogenesis, which is recognized in hilar type squamous cell carcinoma. To date, the association between a honeycombed lesion and lung cancer has been poorly described. Here we have presented clear evidence of the association of this carcinoma with the honeycombed lesion.

Aged↗

PubMed2002

The UPAO test in preoperative evaluation for major pulmonary resection: an operative case with markedly improved ventilatory function after radical pulmonary resection for lung cancer associated with pulmonary emphysema.

A 65-year-old man was admitted to our hospital for treatment of a squamous cell carcinoma in his right lung. Respiratory function testing showed an extremely reduced forced expiratory volume in 1 second (FEV1) of 1.0 l (29.9% of predicted), and a reduced FEV1/FVC ratio of 24.1%. Arterial blood gases on room air showed a pH of 7.41, a PaCO(2) of 36.7 mmHg, and a PaO(2) of 79.3 mmHg. To assess the predictive postoperative cardiopulmonary function, unilateral pulmonary artery occlusion (UPAO) testing was performed. In the condition of right main PA occlusion, the mean pulmonary artery pressure (mPAP), cardiac index (CI) and total pulmonary vessel resistance index (TPVRI) was 18 mmHg, 3.2 l/min/m(2) and 443.37 dyne.sec.cm(-5)/m(2), respectively. He underwent a middle lobectomy with combined partial resection of both the upper and lower lobes. He also underwent simultaneous resection of a giant bulla arising from the right upper lobe as lung volume reduction surgery. At 80 days after the operation, his FEV1 rose to 1.88 l, and the PaO(2) on room air was improved to 88.9 mmHg. UPAO testing was suggested to be more useful than routine pulmonary function test to determine the accurate predictive postoperative cardiopulmonary function and to decide indication for a radical operation.

Aged↗