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Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 55 records · Page 3Linked to original sources

Primary structure and autoproteolysis of brevilysin H6 from the venom of Gloydius halys brevicaudus.

The complete amino acid sequence of brevilysin H6 (H6), a zinc-protease isolated from Gloydius halys brevicaudus venom, was determined by a manual Edman degradation method. H6 has an amino-terminal pyroglutamic acid and consists of a total of 419 residues. An N-linked sugar chain is attached at Asn-181. The molecule is composed of three domains (metalloprotease, disintegrin-like and cysteine-rich domains), as commonly found in other high molecular mass metalloproteases from snake venoms. In the absence of calcium ions, H6 is autocatalytically degraded with a half-life of 47 min to give 29 and 45 kDa fragments, which correspond to residues 208-419 and 99-419 of H6, respectively. Thus, the autoproteolysis seemed to start from the cleavage of either the Leu(98)-Leu(99) or Asp(207)-Ile(208) bond. Calcium ions suppressed both the formation of the 45 kDa fragment and the rate of autoproteolysis. Calcium ions also contributed to the stability of H6 against pH, heating, urea and cysteine. More than twenty-five peptide bonds adjacent to hydrophobic residues in the metalloprotease domain were progressively cleaved during the autoproteolysis.

Amino Acid Sequence↗

Difference in the effects of low temperatures on the tension of human pulmonary artery and vein ring segments.

BACKGROUND: Although limited data suggest that pulmonary flushing with organ preservation solutions should not be performed at too low temperatures, the influence of temperature on pulmonary vascular tone is unclear. OBJECTIVE: The purpose of this study was to examine the effect of low temperatures of the tension of human pulmonary artery and vein ring segments and the vascular resistance of perfused rat lungs. METHODS: 5 sets of human pulmonary artery and vein ring segments were suspended from a force displacement transducer at 37, 24 and 8 degrees C, and the effect of 30 mM K(+) on the tension was monitored. The effect of 30 mM K(+) on vascular resistance was also examined at low temperatures in 5 perfused rat lungs. RESULTS: Pulmonary artery segments dilated at 24 degrees C, and more significant vasodilatation was observed at 8 degrees C. In contrast, there was a significant constriction of pulmonary veins at 8 degrees C. Vasoconstriction induced by 30 mM K(+) at 37 degrees C was significantly inhibited at low temperatures in both pulmonary arteries and veins. In rat lungs, perfusion at 8 degrees C caused a significant increase in pulmonary vascular resistance, even though no further increase was observed in the presence of 30 mM K(+). CONCLUSIONS: Our data indicate that pulmonary arteries dilate and the veins constrict at 8 degrees C and may increase pulmonary vascular resistance. We conclude that the different effect of low temperatures between pulmonary arteries and veins may explain why pulmonary vascular flushing with organ preservation solutions at room temperature is more satisfactory.

Adult↗

Infiltration of CD8+ T cells in non-small cell lung cancer is associated with dedifferentiation of cancer cells, but not with prognosis.

CD8+ T cells infiltrating within cancer cell nests in human colorectal cancer were associated with a favorable patients' survival, suggesting the presence of anti-tumor immunity. The present study was designed to examine this concept in non-small cell lung cancer (NSCLC) by a retrospective analysis of 128 surgically resected cases. Immunohistochemical analysis showed that the number of CD8+ T cells within cancer cell nests in NSCLC was related to the histological subtype (large cell carcinoma or squamous cell carcinoma > adenocarcinoma) and the degree of dedifferentiation (undifferentiated type > differentiated type). In contrast to colorectal cancer, the number of CD8+ T cells in NSCLC had no statistically significant impact on the patients' survival. The present study demonstrated that the degree of infiltration of CD8+ T cells within cancer cell nests is dependent on the dedifferentiation of cancer cells in NSCLC, which could be one of the important aspects for the study of tumor immunity.

Adenocarcinoma↗

Differences in TNF-alpha producing activity from murine peritoneal macrophages induced by lipopolysaccharides of Prevotella heparinolytica and Porphyromonas gingivalis.

We compared the effects of LPSs from P. gingivalis and P. heparinolytica on the induction of tumor necrosis factor-alpha (TNF-alpha) production by murine peritoneal macrophages. The lipopolysaccharide (LPS) preparation from P. gingivalis showed a typical ladder pattern in SDS-PAGE, whereas that from P. heparinolytica formed several stained bands without a ladder pattern. When the macrophages from C3H/HeJ mice were incubated with P. gingivalis LPS, the level of TNF-alpha released in the culture supernatants was significantly higher than that with P. heparinolytica. All tested reagents except genistein strongly inhibited the production of TNF-alpha by the macrophages after induction by either LPS. These results suggested the following possibilities, i) the induction level of TNF-alpha by P. heparinolytica is similar to that of Salmonella minnesota, ii) tyrosine phosphorylation is not the only pathway for the TNF-alpha production induced by these LPSs, iii) different regulatory mechanisms are involved in TNF-alpha production in P. gingivalis LPS stimulated and P. heparinolytica LPS stimulated cells.

Animals↗

MDM2 expression is associated with progress of disease and WAF1 expression in resected lung cancer.

Although MDM2, p21/WAF1, and p53 are considered as regulating each other based on in vitro studies, the relation in human lung cancer is not fully understood. The expressions of these proteins were examined immunohistochemically in 112 resected non-small cell lung cancer specimens and the correlation between them were analyzed. MDM2 was expressed in 45% of all lung cancers. In advanced stage, MDM2-positive cases were observed more frequently than in early stage, showing significant difference. No significant difference was observed in the prognosis of the patients regardless of the expression of any protein. Although no correlation was observed between MDM2 expression and p53 expression, or between p21/WAF1 expression and p53 expression, MDM2 expression was strongly related with p21/WAF1 expression. Therefore, MDM2 expression may relate to the progress of the stage of lung cancer, and MDM2 expression and p21/WAF1 expression may be associated not through the p53-related pathway.

Adenocarcinoma↗

Regulation of the activity and polymerization status of recombinant human cytosolic thymidine kinase by thiols and ATP.

The cDNA clone encoding human thymidine kinase (hTK), was expressed in E. coli using a prokaryotic expression vector, pKK 223-3. The kinetics of the recombinant hTK (rhTK) were similar to those of cytosolic TK but not of mitochondrial TK. rhTK was highly purified in the presence of either ATP or dithiothreitol (DTT). The specific activity of rhTK purified in the presence of ATP [rhTK(ATP)] was lower than that of rhTK purified in the presence of DTT [rhTK(DTT)]. Activity of the purified rhTK(ATP) was enhanced by addition of thiols including DTT, cysteine, homocysteine and beta-mercaptoethanol but inhibited by various sulfhydryl reagents such as 5,5'-dithio-bis(2-nitrobenzoic acid). Hence, it was suggested that rhTK is a thiol-type enzyme. Apparent Mr of purified rhTK(ATP) was 100 kDa, which corresponds to the size of a tetramer (25 kDa subunit), while that of purified rhTK(DTT) was 50 kDa, the size of a dimer. The tetramer form of rhTK(ATP) was converted to the dimer by replacement of ATP by DTT. On the other hand, the dimer form of rhTK(DTT) was converted to the tetramer by addition of ATP. Thus, the catalytic activity of human cytosolic TK might be regulated by thiols as well as ATP via its polymerization status.

Adenosine Triphosphate↗

[An office technique for myringoplasty without the use of fibrin glue].

A simple method for office closure of eardrum perforation using an atero-collagen graft used for dermal defects (Terdermis) without fibrin glue was developed. Eardrum perforations were successfully closed in 71.4% of all cases (63 ears) after the initial treatment. Neither skin incision nor the use of temporal fascial grafts was necessary in this method. The merit of the method is that there is no possibility of blood infection because no blood materials are used.

Adolescent↗

[Assessment of systematic nodal dissection by VATS lobectomy for lung cancer].

The feasibility of the complete systematic nodal dissection by the video-assisted thoracic surgery was prospectively assessed in 22 cases of clinical stage I lung cancer (16 right, 6 left cases). Resection of the designated lobe with the mediastinal lymph node dissection was carried out by the small thoracotomy with the aid of the thoracoscope, followed by the standard surgery to verify the completeness of systematic nodal dissection. Although residual lymph nodes were found in 14 of 22 cases, the residual rate was 2.9% and 2.7% by the number and 2.3% and 2.1% by the weight in right and left cases, respectively. Average time and hemorrhage for performing the procedure were 196 minutes, 216.7 minutes and 157.5 g, 145 g in right and left cases, respectively. As a consequence, sufficient systematic nodal dissection in lung cancer was suggested to be feasible by VATS lobectomy.

Humans↗

[A case of right B2 hillar lung cancer treated by sleeve segmentectomy].

A 47-year-old male, a heavy smoker, was referred to our hospital after Class IV was detected by screening of sputum cytology. His chest X-ray film showed no abnormalities, but bronchoscopy revealed a small nodular lesion at the orifice of right B2. Squamous cell carcinoma was diagnosed by transbronchial biopsy. The clinical stage was I (T1N0M0), and S2 sleeve segmentectomy with lymph node dissection (R 2 b) was performed. The pathological stage was I (T1N0M0), and it was confirmed as early hilar lung cancer. There were no post operative complications and he is well without any evidence of recurrence 5 months after surgery. It may well be considered that this segmental bronchoplastic procedure is useful for cases with early stage squamous cell carcinoma of the segmental bronchus to preserve pulmonary function.

Carcinoma, Squamous Cell↗

[Strategy of treatment for roentgenographically occult lung cancer].

Roentgenographically occult bronchogenic squamous cell carcinomas(ROCs) are very small hilar type lung cancer that grow superficially and localize mainly in the bronchial wall, and these patients are expected to have an excellent prognosis after resection. When a ROC is limited within bronchoscopic visibility and less than 10 mm in longitudinal extension and its bronchoscopic findings are slight thickening and flat or wavelet, the tumor is a good candidate for photodynamic therapy. When a ROC is limited within bronchoscopic visibility, the tumor is a good candidate for segmentectomy with curative intent. The tumor invading beyond bronchial wall and/or nodal involvement should be treated by standard operation.

Bronchoscopy↗

[A case of mediastinal pseudocyst with unusual cystic findings in computed tomography].

We report here a case of mediastinal pseudocyst with unusual CT findings. A 25-year-old woman was admitted to our hospital due to a chest abnormal shadow. She had a cystic mass which was located at anterior mediastinum and was adjacent to great vessels broadly without invasive findings. The intraoperative and histological findings revealed that the cystic mass was a pseudocyst which had been generated by the rupture of a thymic cyst to the mediastinum.

Adult↗

[The lung transplantation has come to be done in Japan].

After the establishment of transplantation law, the right pulmonary transplantation was done from the brain dead donor for the first time in Japan at the attached hospital of Institute of Development, Aging and Cancer, Tohoku University on March 29, 2000. The woman in 30's had been deteriorated from progressive lymphangiomyomatosis since 1984. She was waiting for the right lung transplantation in the related hospital of the Institute Hospital since May, 1999. A brain dead donor appeared in Tokyo. After receiving the information from Japan Organ Transplant Network, we immediately started for Tokyo in order to procure the lung. We carried the right lung by Shinkansen. The lung of the donor was transplanted to the patient under the partial extracorporeal circulation on March 29, 2000. The total operating time was 6 hours and 7 minutes: 5 hours and 20 minutes for total ischemic period of the lung and 2 hours and 7 minutes for using extracorporeal circulation. The total amount of bleeding during the operation was 3,695 ml. Postoperative course of the transplanted patient was fair except chylothorax in the operated side, which was successfully controlled by intrathoracic infusion with OK-432. The transplanted patient was discharged from the hospital after 75 days postoperatively.

Adult↗

[The application of poly (L-lactide) sternal coaptation pins for median sternotomy].

Poly (L-lactide) sternal coaptation pin has been developed as an assistant material for the fixation of sternum. We used the novel material to a patient who underwent median sternotomy. A 21-year-old male was suspected to have invasive thymoma in the anterior mediastinum. The median sternotomy was indicated as an approach for the resection of tumor. Tumor was completely resected and there was no invasion to sternum. For the fixation of sternum, three poly (L-lactide) sternal coaptation pins were inserted in the bone marrow of sternum and five stainless steel wires were used as conventional procedure. Sternum was adapted without slippage and no complication from the material was observed in the post-surgical period. The application of poly (L-lactide) sternal coaptation pin is a good option for ensuring the fixation of sternum.

Adult↗

[Successful treatment for descending necrotizing mediastinitis: a case report].

A 21-year-old female was admitted to our hospital because of high fever, neck swelling, and dyspnea. She was diagnosed as descending necrotizing mediastinitis (DNM) extended from odontogenic infection. On the day of admission, she underwent cervical drainage. Next day, the CT scan showed an abscess below the tracheal bifurcation and bilateral pleural effusion. Mediastinal drainage was performed through a right thoracotomy, and a left thoracic tube was inserted. Anaerobic Peptostreptococcus was found with bacteriological culture. After the mediastinal drainage, bilateral thoracic irrigation was performed through the thoracic tubes. Left thoracic tube was removed on the 8th day and right one was removed on the 20th day after the thoracotomy. She was discharged on the 42nd day. DNM is relatively rare, but it is lethal disease with high mortality. Immediate and sufficient mediastinal drainage is indispensable for the disease.

Abscess↗

[Reconstruction of chest wall using myocutaneous flap].

Reconstruction of chest wall using myocutaneous flap has been performed in 2 cases. A 72-year-old female referred to our hospital for locally recurrent left breast cancer without any distant metastases. The other patient was a 77-year-old female, having locally recurrent liposarcoma of the left lateral chest wall. Chest wall was resected with wide margin of normal tissue, and myocutaneous flaps of latissimus dorsi were used for reconstruction of skin defect (13 x 8 cm and 14 x 10 cm) in both cases. Although additional split-thickness skin graft was required for one of them, myocutaneous flaps were useful for the reconstruction of widely defected chest wall. By using this technique, wider margin can be obtained, which could decrease the risk for local recurrence of malignant tumor.

Aged↗

[Present condition of lung transplantation candidates in eastern Japan].

We investigated the present condition of lung transplant candidates and the familiarity of doctors in eastern Japan by questionnaire. We shipped questionnaires to 614 hospitals in the Hokkaido district, the Tohoku district, the Kanto district and Niigata Prefecture, a received responses from 216 departments (200 hospitals). The percentage of respondents was 32.6%. There were 191 lung transplant candidates, 97 men and 94 women, in the past two years. Moreover, there were 45 patients with primary pulmonary hypertension (PPH), 38 with idiopathic pulmonary fibrosis, 23 with pulmonary emphysema, 20 with pulmonary lymphangiomyomatosis, among others. Currently, however, there are 88 patients who are lung transplant candidates, a large number, in eastern Japan. On the other hand, only 38 of 68 departments had informed their patients about lung transplantation. It was a lamentable result for transplant surgeons, and points urgently to the importance of giving information about lung transplantation.

Adolescent↗

[Clinical analysis of patients referred for lung transplantation in eastern Japan].

We investigated the indications for lung transplantation (LTx) in Japan and discussed questions regarding the current Japanese criteria of LTx. This study examined 37 patients referred to our institute for LTx. Among these patients, there were 11 cases of primary pulmonary hypertension (PPH), 6 of lymphoangiomyomatosis (LAM), 4 of Eisenmenger's syndrome, 3 of bronchiolitis obliterans, 2 each of bronchiectasis, idiopathic pulmonary fibrosis (IPF), and pneumoconiosis, and 7 of other diseases. The most frequent age group was 30-39 years (12 cases, 32.4%), and more than half of the patients were female (22 cases, 59.5%). The regions of residence of the patients were Tohoku (19 patients), Kanto (16), and Chubu (2). Patients were referred from all over eastern Japan. On evaluation, LTx was contraindicated in 5 cases, in 4 of which mechanical ventilation had been installed before consultation with us. Six patients died before registration on the Japan Organ Transplant Network (JOT). 6 transplant candidates were registered with JOT, but one (PPH) died after 6 months of waiting, and one (LAM) received a lung transplant from a brain dead cadaver donor. We propose to reform and clarify the Japanese criteria for LTx-both indications and contraindications, to include such indications as a survival probability of less than two years, and such contraindications as mechanical ventilation. Early consultation at LTx centers was hoped for, in accordance with the International Guidelines and a transplant window.

Adolescent↗

A randomized trial of postoperative CDDP-based chemotherapy/chemoradiotherapy vs short-term immunochemotherapy in lung cancer.

BACKGROUND: Although a few reports indicated some benefit to survival, the effect of adjuvant therapy for the patients with resected lung cancer was still controversial. The aim of our study was to evaluate survival advantage of CDDP-based adjuvant therapy compared with short-term immunochemotherapy. METHODS EXPERIMENTAL DESIGN: prospective randomized trial. PATIENTS: from 1990 through 1994, 94 patients were registered. Forty-seven patients were randomly assigned to each group, i.e., CDDP-based therapy group (CB Group, CDDP+VDS+tegafur+OK-432 or CDDP+OK-432+mediastinal irradiation) or immunochemotherapy group (IC Group, tegafur+OK-432). PATIENTS in both groups were followed at 4-month intervals with the routine follow-up program of our department. RESULTS: No significant difference was observed between the patients' characteristics of two groups. Compliance of the regimen in each group was 79% in CB Group and 85% in IC Group. No treatment-related death was observed. Five-year survival rates of CB Group and IC Group were 49% and 51%, and 5-year disease-free survival rates were 46% and 44%, respectively. There were no statistical differences between the two groups. Furthermore, no survival differences could be found between CB Group and IC Group in any subgroup of patients. CONCLUSIONS: Both of these regimens were feasible. However, we have not observed any survival benefit in the CB Group in any subgroup, so far. Induction therapy, new chemotherapeutic agents, or anti-angiogenetic a agents may improve the survival of surgically treated lung cancer patients.

Adenocarcinoma↗