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Biomedical subjects

M Gomibuchi

Publications and source records attributed to M Gomibuchi.

At least 19 recordsLinked to original sources

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non-fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription-polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor-bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

Adenocarcinoma↗

Aerogenous spread of primary lung adenocarcinoma induces ultrastructural remodeling of the alveolar capillary endothelium.

To determine whether pulmonary alveolar capillaries manifest ultrastructural remodeling at areas of neoplastic invasion of primary lung adenocarcinomas, we examined 17 well-differentiated adenocarcinomas of lung (2 bronchioloalveolar and 15 papillary adenocarcinomas) by electron microscopy. The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was demonstrated by immunohistochemical stainings. VEGF messenger RNA (mRNA) isoforms were detected by reverse-transcription polymerase chain reaction (RT-PCR) in alveolar walls microdissected from normal and tumor-associated tissues. Cytoplasm of neoplastic cells expressed VEGF protein in all patients. Endothelial cell nuclei of alveolar capillaries showed positive reaction for PCNA. Alveolar capillary lumina were distended like venules, and some intercellular junctions remained open. The cytoplasm of the capillary endothelial cells was enlarged and developed numerous organelles such as Weibel-Palade bodies and vesiculovacuolar organelles, in contrast to marked attenuation in their normal counterpart. Capillary sprouting occurred from proper alveolar capillaries in 2 patients. Cytoplasmic segments became extremely attenuated and developed diaphragm-like fenestrae in 65% of the patients. A relatively higher expression of diffusable isoforms of VEGF mRNA was seen in the tumor-bearing alveolar walls than in normal walls. Expression of KDR (one of the VEGF receptors) mRNA in tumor exceeded that in normal tissues. These results suggest that diffusable isoforms of VEGF mRNA released from the neoplastic cells are deeply involved in the induction of growth activity of alveolar capillary endothelial cells as much as in the characterization of tumor-associated microvessels in primary lung adenocarcinomas.

Adenocarcinoma, Bronchiolo-Alveolar↗

Investigation of coronary artery bypass grafting for a patient with myelodysplastic syndrome.

A 79-year-old male with unstable angina, who had myelodysplastic syndrome (MDS), was treated with coronary artery bypass grafting (CABG). MDS causes refractory anemia accompanied by various degrees of granulocytopenia and thrombocytopenia. Pancytopenia caused by MDS may complicate patients with major infections and bleeding during cardiac surgery. There were very few patients with MDS who had undergone open-heart surgery. Three case studies, including this study, had reported successful cases of CABG in patients with MDS and the analogous diseases of MDS. We used granulocyte colony-stimulating factor (G-CSF), red blood cells (RBCs) and platelets transfusions in peri-operative state. We did not need a large amount of transfusion of RBCs and platelets in intra-operative and postoperative states. We had prevented major bleeding and severe wound infections in the acute postoperative state.

Aged↗

Mosaic-like distribution of endothelial cell antigens in capillaries and juxta-alveolar microvessels in the normal human lung.

The distribution patterns of endothelial cell antigens, including thrombomodulin and von Willebrand factor (vWf), were studied in normal lung tissues obtained from distant areas of solitary nodules (seven adenocarcinomas and four hamartomas). By single immunoalkaline phosphatase and dual immunofluorescence stainings, the plasma membranes of alveolar capillary endothelium showed linear distribution of thrombomodulin, but their cytoplasm was rarely reactive for vWf (thrombomodulin-dominant pattern). Microvessels with a diameter larger than 10 microm located in the connective tissue zones demonstrated band-like reaction for vWf in their cytoplasm, and their plasma membranes often lacked reactivity for thrombomodulin (vWf-dominant pattern). The juxta-alveolar microvessels located along the borders between the alveolar- and connective-tissue zones showed mosaic-like pattern of distribution for these antigens. The pulmonary venules and peribronchial microvessels measuring up to 40 microm in diameter, demonstrated the expression of thrombomodulin along the plasma membrane, and that of vWf in the cytoplasm. Capillaries of the bronchial circulation were also characterized by mosaic-like pattern of distribution. Both antigens were often expressed in a single cytoplasmic segment. The heterogeneous distribution pattern of these antigens suggests topographic difference in endothelial cell function to maintain coagulatory and anticoagulatory balance in the normal human lung.

Adult↗

Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels.

Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones), including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring <10 microm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A- and C-zones, and measuring up to 40 microm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

Adult↗

[Multiple lungs tumors found 17 years after hysterectomy--a case of benign metastasizing leiomyoma].

The patient is a 50-year-old female who presented with cough. A chest X-ray showed bilateral multiple modular shadows. Even though a diagnosis of metastatic lung tumors was strongly suspected no primary lesion could be detected on close examination. Therefore, an exploratory thoracotomy, and histopathological examination of a specimen obtained from a resected tumor were carried out. The resected tumor revealed pathological proliferation of spindle cells without high cellularity or mitosis with nuclear atypism. The patient had a history of surgery for uterine leiomyoma at the age of 33. The histopathological characteristics of the resected lung tumors were remarkably similar to those of the previously resected uterine leiomyoma. In addition, the serum levels of sex hormones, including LH, measured after lung surgery, were within normal range suggesting the possibility of the lung tumors being metastatic. The residual lung tumors did not show any increase in size 26 months after surgery. Therefore, these lung tumors could be considered as lung metastases from a low grade malignant uterine leiomyoma (benign metastasizing leiomyoma).

Female↗

[Ethanol injection therapy to the lung cancer].

Ethanol injection was tried in patients who underwent exploratory thoracotomy. There were 4 males and 1 female, adenocarcinoma in 3 cases, large cell carcinoma in 1 case, and metastatic lung cancer in 1 case. We grasped the lung included the tumor, and injected ethanol directly into the tumor. Maximum dose of injected ethanol was within 10 ml. There were no any complications postoperatively in all patients. Postoperative course was followed by means of chest CT. Three patients whose preoperative cancer stage was early stage gained good results in local control, two patients whose preoperative cancer stage was stage III B in one patient and metastatic cancer rapidly growing in other patient had no effects. Ethanol injection into the lung tumor was easy to perform and safety, and has direct effect in local control of the tumor in especially small sized.

Adenocarcinoma↗

[Mediastinal lymph-node carcinoma with no apparent primary lesion].

To determine the clinical characteristics of cases of hilar or mediastinal lymph-node cancer in which the primary lesion was not found; reports of 36 such cases were identified. The patients in those cases comprised 29 men and 7 women, whose average age was 58.4 years. The malignancies were found in hilar lymph nodes in 15 patients, mediastinal lymph nodes in 16, and both hilar and mediastinal lymph nodes in 4; 14 were adenocarcinomas, 4 were squamous-cell carcinomas, and 4 were small-cell carcinomas. The average length of cancer-free survival after surgery was 28.9 months, and the maximum was 9 years. After the affected hilar and mediastinal lymph nodes had been resected the clinical appearance of these patients was the same as if the primary tumor had been removed. We therefore believe that many patients given a diagnosis of cancer with metastases to hilar or mediastinaly lymph nodes and in whom the primary tumor cannot be located in fact have primary cancer of the lymph nodes, and that this condition should be called "primary mediastinal lymph-node carcinoma".

Adult↗

[Four cases of adrenal tumor discovered through examination before surgery for lung cancer].

Preoperative CT and Ultrasonography (US) showed adrenal tumors in four patients with lung cancer. Although metastasis of the cancer to the adrenal gland was suspected, a definitive diagnosis could not be made by CT and US alone. MRI is as ineffective as CT and US. Needle biopsy is useful if tumor cells are detected, but not unless they are discovered. Surgery, therefore, is necessary to establish the final diagnosis. (Adrenalectomy was performed on all cases, one of which had metastasis). No particular complications occurred after adrenalectomy. Adrenalectomy was considered unavoidable to determine stage and treatment policies in patients suspected of metastasis in imaging diagnosis.

Adenocarcinoma↗

[Evaluation of the prognosis of patients with stage I non-small cell lung cancer with respect to predicted postoperative lung function].

One hundred and forty patients underwent absolute curative resction for stage I non-small lung cancer from 1982 to 1993 at our department. For these, prognosis and changes in quality of life (QOL) were evaluated retrospectively with respect to the predicted postoperative lung function. The average age of the patients was 62 years (range 31 to 84 years), and 103 males and 37 females were included. Seventy-five of the patients had adenocarcinoma, 61 squamous cell carcinoma, and 4 large cell carcinoma. These 140 patients were classified into two groups, H and N, according to the predicted postoperative %FEV1.0 and %VC. Group H patients (n = 39) had a predicted %FEV1.0 and/or %VC of 55% or less for postoperative respiratory disease. Group N patients (n = 101) had a predicted %FEV1.0 and %VC of 56% or more for expected normal respiratory conditions postoperatively. Group N patients showed a 98% one-year survival rate, and 72% five-year survival rate and good QOL postoperatively. On the other hand, group H patients showed 86% and 45% one- and five-year survival rates respectively, the same as those predicted for patients with stage II non-small cell lung cancer. Furthermore, group H patients more than 70 years old showed 80% and 17% one- and five-year survival rates, the same as those predicted for patients with stage IIIA non-small cell lung cancer, and poor prognosis in comparison with that of the group N patients more than 70 years old. Then, QOL was investigated one year postoperatively. The group H patients showed deterioration of performance status in comparison with the group N patients. Since there was a high incidence of postoperative respiratory disease in the patients with a predicted %FEV1.0 and/or %VC of 55% or less, physicians should avoid extended lung resection, which might cause deterioration of the cardiopulmonary reserve volume, in patients in whom respiratory disease is predicted to occur, particularly for patients more than 70 years old. In conclusion, physicians should consider limiting surgical intervention to preserve lung volume and QOL of patients more than 70 years old with restricted cardiopulmonary function.

Adult↗

[Analysis of risk factors for development of bronchopleural fistula after pneumonectomy for lung cancer].

Bronchopleural fistulas (BPF) developed in six (7.9%) of 76 patients who underwent a pneumonectomy for treatment of lung cancer. Five patients (18.2%) underwent a right pneumonectomy and one (3.7%) a left pneumonectomy. All patients were male, had squamous cell carcinoma, and were diagnosed as having BPF within one month after pneumonectomy. Their average age was 60.2 years. Univariate analyses related to development of BPF showed that significant risk factors were preoperative infection (Chi-square test; p < 0.001), right pneumonectomy (Chi-square test; p < 0.05), and metastasis to a subcarinal lymph node (Chi-square test; p < 0.05). However, sex, age, operating time, amount of blood loss during surgery, amount of blood transfused during surgery, history of smoking, degree of lymph node dissection, degree of curability, performance of combined resection, histologic type of tumor, tumor size, presence of residual tumor at the bronchial stump, and suturing method were not significant risk factors for development of BPF. Our stepwise regression analysis related to development of BPF showed that preoperative infection, metastasis to a subcarinal lymph node, right pneumonectomy, and combined resection were significant risk factors. Sometimes it is difficult to preserve the bronchial arteries upon the dissection of metastatic subcarinal lymph nodes which tightly adhere to the bronchial sheath. Moreover, after a conventional right pneumonectomy, the bronchial stump protrudes into the pleural cavity and is not covered by any tissue. Ligation of the bronchial arteries or protrusion of the bronchial stump into the right pleural cavity reduces the blood supply to the bronchial stump to a very low level and causes development of BPF. Therefore, we suggest that control of preoperative infection, wrapping of the bronchial stump, and preservation of the bronchial arteries during mediastinal lymph node dissection are important to prevent development of BPF.

Bronchial Fistula↗

[Changes in ventilation efficacy due to pulmonary resection and postoperative exercise restricting factors].

An exercise test was performed before and after surgery on patients who underwent at least a lobectomy, and changes in ventilation efficacy due to pulmonary resection (n = 40) and postoperative exercise restricting factors (n = 11) were investigated. When the degree of exercise was the maximal, the tidal volume (TV), expired volume per minute (VE), VO2 and VO2 significantly decreased after surgery. As a result of comparing preoperative values corresponding to postoperative VO2 max, both VE and VCO2 were found to increase. When the preoperative exercise load was the same as the postoperative maximum load, there was no significant difference in VE or VCO2, but VO2 decreased postoperatively. Cumulative VE, VO2 and VCO2 values increased postoperatively. In the 11 patients in whom the parameters were investigated preoperatively and postoperatively using an invasive method, the VO2 max, cardiac index (CI), stroke volume index (SVI) and TV decreased when the degree of exercise was maximal. There was no significant difference in total pulmonary vascular resistance (TPVR), heart rate (HR) or respiratory rate. There were significant correlations among HR, mean pulmonary arterial pressure (mPAP) and VO2 before and after surgery (R = 0.88, 0.78 and 0.77 respectively). The ventilation efficacy during exercise decreased after pulmonary resection, and anaerobic metabolism increased at the same exercise load. When the degree of exercise was maximal, mPAP was maintained, SVI decreased, HR was unchanged, and CO and VO2 decreased. These data suggested that mPAP and HR are postoperative exercise restricting factors.

Adult↗

[Aneurysmal bone cyst of the left 5th rib].

A case of aneurysmal bone cyst of the left 5th rib is reported. A 57-year-old male complained of palpable lump and pain on his back. Chest X ray and CT showed expansive tumor arid pathological fracture of the left 5th rib. The tumor and the adjacent segments of the 4th and 5th ribs were resected en bloc. The pathological examination showed multiple blood filled spaces and fibrous trabeculae, confirming the diagnosis of aneurysmal bone cyst. He has been followed up for 3 years and 6 months with no signs of recurrence.

Bone Cysts, Aneurysmal↗

[Changes of respiratory function after lung resection--taking notice of changes during exercise test and anaerobic metabolism].

Changes in the following respiratory functions during exercise test were examined before and after surgery in 31 patients undergoing pulmonary resection: VE, VCO2, and VT at a constant VO2 during exercise; and VO2, VCO2, VE and VT at constant loading (watt). At the level of 300 and 500 ml/min of VO2, VCO2 showed no significant difference before and after the operation but when VO2 reached 700 ml/min. VCO2 showed a significant increase from 542.0 +/- 78.3 ml/min to 595.5 +/- 85.2 ml/min postoperatively (p < 0.05). When exercise load was 45 watt, VE showed no significant difference before and after the operation, but when exercise load was 60 watt, VE showed a significant increase from 30.16 +/- 5.38 L/min to 33.89 +/- 4.69 L/min postoperatively (p < 0.005). These results indicated an early acceleration of ventilation in low load postoperatively. With respect to anaerobic metabolism, AT, oxygen uptake to work rate (delta VO2/delta WR), and our proposed index calculated as an area using the cumulative oxygen uptake were compared pre- and postoperatively. The results indicated that AT decreased significantly from 716.0 +/- 190.8 ml/min to 528.4 +/- 150.7 ml/min (p < 0.001), and delta VO2/delta WR also decreased significantly from 13.5 +/- 4.0 ml/min/W to 11.3 +/- 4.2 ml/min/W (p < 0.05). The index calculated as area showed a significant increase from 4070.2 +/- 3468.8 to 5095.3 +/- 3854.5 (p < 0.05). All these findings indicated that anaerobic metabolism increases postoperatively. Accordingly we conclude that postoperative increase of anaerobic metabolism causes postoperative acceleration of ventilation in low load.

Adult↗

Characterization of ganglioside expression in human melanoma cells: immunological and biochemical analysis.

The expression of N-glycolylneuraminic acid (NeuGc)-containing gangliosides in human melanoma cells grown both in culture and as xenografts in athymic (nu/nu) mice was analyzed extensively with specific mouse monoclonal antibodies (MAbs). Three MAbs (GMR8, GMR14, and GMR3) specific for GM3(NeuGc), GM2(NeuGc), and GD3(NeuGc-NeuGc-), respectively, were used. Significant differences were observed in the ganglioside compositions between the cultured cells in vitro and the tumors grown in vivo. The major difference was that the cells cultured in serum-free medium did not express any NeuGc-containing gangliosides, whereas those grown in nude mice expressed a number of NeuGc-containing gangliosides, namely GM3(NeuGc), GM2(NeuGc), GD3(NeuAc-NeuGc-), GD3(NeuGc-NeuAc-), and GD3(NeuGc-NeuGc-). The structures of these gangliosides were also determined chemically. No activity of CMP-NeuAc hydroxylase was demonstrated either in the melanoma cells cultured in vitro or in those grown in nude mice, suggesting that these cells incorporated NeuGc-containing glycoconjugates from the mouse sera and converted them to other NeuGc-containing gangliosides. The mouse sera contained only GM2(NeuGc), but not the other NeuGc-containing gangliosides or any NeuAc-containing gangliosides.

Animals↗

[Treatment of thoracic malignancy accompanied with cardiovascular disease].

We treated 10 cases of thoracic malignancy accompanied with cardiovascular disease. Among thoracic malignancy, 7 cases were lung cancer and 3 were esophageal cancer. Accompanied cardiovascular diseases were ischemic heart disease (2 cases), valvular disease (3 cases), WPW syndrome (1 case), aortic aneurysm (4 cases). The mean age was 66, ranged from 51 to 79. The simultaneous occurrence of the two lesions were observed in 6 cases and thoracic malignancy was diagnosed after a varying interval of time following surgery of cardiovascular disease in 4 cases. In cases of thoracic malignancy accompanied with heart disease, the treatment of heart disease should precede the operation of malignant disease to reduce the risk of surgery. For the patient with esophageal cancer, posterior mediastinal esophagostomy should be applied who may have heart surgery in future. In cases of coexisting malignancy and aortic aneurysm, the priority of treatment should be determined considering the size of aneurysm. If the transverse diameter of aneurysm is larger than 7 cm, there is a high risk of rupture, so surgery for the aneurysm precedes operation of malignant diseases. It is desirable to avoid concomitant operation of malignancy and cardiovascular disease.

Aged↗

[Exercise test to predict postoperative complications in patients with impairment of pulmonary function].

We studied the prediction of postoperative complications in patients whose predicted postoperative FEV1.0% and/or %VC were below fifty. Preoperative exercise tests were performed in 88 cases mainly old patients of age or with impaired pulmonary function; 57 were lobectomies, 10 were bilobectomies and 21 were pneumonectomies. Predicted postoperative FEV1.0% and/or %VC were below fifty in 29 cases consisting of 12 lobectomies, one bilobectomy and 16 pneumonectomies. Among these 29 patients, thirteen suffered postoperative complications (A group) and sixteen did not (B group). All five cases of operative death (death within 30 days after operation) were included in the A group. The prediction of postoperative complications in cases of which pred. postope, FEV1.0% and %VC were fifty or over (C group) was also studied. The results were as follows; (1) The percentage of complications among A and B groups was higher than that among C group but no statistical difference could be found. (2) In the A group, the number of pred. postope. FEV1.0% and/or %VC had little correlation to complications. (3) Statistical differences between A and B group were found in submax VO2 (p < 0.05), VO2/VE at AT (p < 0.001) and VCO2/VE at submaximal exercise (p < 0.001). (4) Cardiac output ratio of maximal exercise to rest had marked correlation to complications (p < 0.001) in C group but had no correlation in the A and B groups. (5) The three items of A and B groups, submax VO2 < 500 ml/min/m2, VO2/VE at AT < 40 ml/l and submax VCO2/VE < 25 ml/l, showed high correlation to operative death (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗