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Biomedical subjects

T Funatsu

Publications and source records attributed to T Funatsu.

At least 55 records · Page 3Linked to original sources

[Surgical treatment of lung cancer with mediastinoscopic positive lymph nodes].

There are no definite criteria for the indication of surgery in lung cancer with mediastinal lymph node involvement. During the past 20 years, 100 patients (76 patients with adenocarcinoma and 24 patients with squamous cell carcinoma) have undergone thoracotomy for lung cancer with mediastinoscopic positive lymph nodes at our hospital. Of these, relatively curative resection was performed on 13 patients. The 5-year survival rate in these 13 patients was 28%, which was significantly higher than the 0% in 42 patients with relatively non-curative resection and the 0% in 26 patients with absolutely non-curative resection. The 5-year survival rate was 9% in both T1 (n = 14) patients and T2 (n = 37) patients. No T3 (n = 21) and T4 (n = 9) patients survived 3 years. The 5 year survival rate in patients with squamous cell carcinoma was 12% and that in patients with adenocarcinoma was 0%, but there was no significant difference. The survival rates of T1 and T2 patients were significantly higher than that of T3 patients (p less than 0.02 and p less than 0.005) respectively. Contralateral mediastinal lymph node metastasis (N3) was observed significantly more frequently in patients with adenocarcinoma (38%) than in those with squamous cell carcinoma (13%), but there was no significant difference in the survival rate. In N2 patients, the survival rate was compared between those with mediastinal nodal involvement of an early stage (N2-1) and those with lymph node metastasis of more advanced stage (N2-2) according to the lobe bearing the primary cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Elastic filaments in skeletal muscle revealed by selective removal of thin filaments with plasma gelsolin.

Muscle needs an elastic framework to maintain its mechanical stability. Removal of thin filaments in rabbit skeletal muscle with plasma gelsolin has revealed the essential features of elastic filaments. The selective removal of thin filaments was confirmed by staining with phalloidin-rhodamine for fluorescence microscopy, examination of arrowhead formation with myosin subfragment 1 by electron microscopy, and analysis by SDS-PAGE. Thin section electron microscopy revealed the elastic fine filaments (approximately 4 nm in diameter) connecting thick filaments and the Z line. After removal of thin filaments, both rigor stiffness and active tension generation were lost, but the resting tension remained. These observations indicate that the thin filament-free fibers maintain a framework composed of the serial connections of thick filaments, the elastic filaments, and the Z line, which gives passive elasticity to the contractile system of skeletal muscle. The resting tension that remained in the thin filament-free fibers was decreased by mild trypsin treatment. The only protein component that was digested in parallel with the decrease in the resting tension and the disappearance of the elastic filaments was alpha-connectin (also called titin 1), which was transformed from the alpha to the beta form (from titin 1 to 2, respectively). Thus, we conclude that the main protein component of the elastic filaments is alpha-connectin (titin 1).

Actin Cytoskeleton↗

Development of a new surgical procedure for repairing tracheobronchomalacia.

We have developed a new surgical method for repairing tracheobronchomalacia. In experiments on dogs we tried external fixation of Marlex mesh (Bard Cardiosurgery Division, Bellerica, Mass.) on the trachea. We first made models of tracheomalacia by making fractures or resections in intrathoracic tracheal cartilages and then made an external fixation of Marlex mesh on the malacic segments of the trachea. In 11 dogs Marlex mesh was sutured onto the trachea with absorbable thread. The trachea was firmly supported after 2 to 6 months, compared with three controls in which no external fixation was made. However, mucosal defects associated with ischemia caused by the suture developed in four of the 11. In 13 more dogs Marlex mesh was bonded to the trachea with fibrin glue. After 3 to 8 months the supporting strength of the trachea increased up to the level of the normal trachea. There was no evidence of inflammation or of mucosal defects. Therefore Marlex mesh was applied to a 44-year-old-man who had experienced frequent attacks of cough syncope. After the operation the attacks of cough syncope and collapsing of his airway disappeared completely.

Adult↗

[Flow cytometric analysis of cellular DNA content of lung cancer with reference to survival].

The cellular DNA content of lung cancer were measured by flow cytometry on 223 paraffin-embedded specimens prepared from resected lung carcinomas. According to the histological type of lung cancer, the mean values for the DNA Index were 1.41 in adenocarcinoma, 1.39 in squamous cell carcinoma, 1.33 in large cell carcinoma and 1.84 in small cell carcinoma. The DNA Index of small cell carcinoma was thus slightly higher than that of the other histological types, without statistically significant difference. Of 223 lung carcinoma cases, 131 (59.1%) were DNA aneuploidy and 92 (40.9%) were DNA diploidy. DNA aneuploidy was found in 56.1% of adenocarcinomas, 59.5% of squamous cell carcinomas, 53.3% of large cell carcinomas and 100% of small cell carcinomas. According to the staging of the lung cancer, the mean values of the DNA Index were 1.40 in stage I, 1.46 in stage II, 1.36 in stage IIIA, 1.48 in stage IIIB and 1.48 in stage IV. No statistically significant differences were found among these stages. DNA aneuploidy was found in 57.1% of stage I, 57.9% of stage II, 54.7% of stage IIIA, 60.0% of stage IIIB and 75.0% of stage IV. The correlation of DNA content with survival were investigated in 94 cases with stage I non-small cell carcinoma which underwent absolute curative resection. Of 94 cases, the 5-year survival rate of 40 cases with DNA diploidy was 81.1% and a mean survival time 111 months, while this one of the remaining 54 with DNA aneuploidy was 58.4% and a mean survival time 80 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗

[Experimental and clinical results of tracheal prosthesis].

Prosthetic reconstruction of the trachea was performed experimentally in mongrel dogs. Neville's prosthesis, which we used initially, has insufficient elasticity and flexibility. As a result, migration was observed after the reconstruction. To prevent such migration, we wrapped the prosthesis in Marlex mesh. Nevertheless, dehiscence and local infection occurred at the anastomotic site. We have developed a new Katsura prosthesis which is made of silicone rubber and has good elasticity and flexibility. However, the Katsura prosthesis was also unable to prevent dehiscence and local infection at the anastomotic site in the experiment. We have thus tested successive models of the Katsura prosthesis (model I-model V). Recently, we wrapped the prosthesis of model V in pedicled omentum instead of Marlex mesh to prevent the spread of infection to the mediastinum. In clinical cases who had a large surgical defect of the trachea and difficulty of primary anastomosis, we performed prosthetic reconstruction. We used Neville's prosthesis in 7 cases and the Katsura prosthesis in 5 cases. Severe complications were observed, such as arterial erosion and migration of the prosthesis. All the cases have died, although 5 cases survived for more than 1 year, and the longest survival time was 43 months. In the future, we hope that an ideal substitute for the trachea will be found and that prosthetic reconstruction will be able to safely performed, as in the case of vascular prosthesis.

Animals↗

[Clinical evaluation of serum CA130 in patients with lung cancer].

CA130 is a glycoprotein which is recognized by monoclonal antibodies-(130-22 and 145-9) produced by immunization with human lung adenocarcinoma cell line (PC-9). CA130 is considered to be a new tumor marker, different from CA125, since it has a separate antigenic determinant. We used the D-7111 kit (Daiichi Radioisotope Laboratories, Ltd.) to measure the serum level of CA130 in 290 patients with lung cancer, 171 patients with noncancerous lung disease (N-CLD) and 93 healthy adults. In addition, CEA, CA19-9, CA125 and sialyl SSEA-1 antigen (SLX) were also measured for the same serum samples when possible. The cutoff level for CA130 was 35 U/ml. The overall positive rates for CA130 were 32% in the lung cancer patients, 23% in the N-CLD patients and 0% in the healthy adults. The positive rate in the lung cancer patients was significantly higher than in the N-CLD patients (p less than 0.05). As a function of the histological type of lung cancer, the positive rates for CA130 were 44% in 120 patients with adenocarcinoma, 17% in 115 patients with squamous cell carcinoma, 33% in 36 patients with small cell carcinoma, 42% in 12 patients with large cell carcinoma and 29% in 7 patients with miscellaneous cell type. The positive rate in the patients with adenocarcinoma was significantly higher than in the patients with squamous cell carcinoma (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

Age- and sex-specific cumulative rate and risk of ATLL for HTLV-I carriers.

We have surveyed the incidence of adult T-cell leukemia/lymphoma (ATLL) in an endemic area of 290,464 inhabitants for 7 years. We now revise our previous results on the basis of additional findings and estimate the age- and sex-specific cumulative rate for HTLV-I carriers, the adoption of which is recommended by current cancer epidemiology as a new age-standardized incidence rate. An unequivocal age-dependent increase in seroprevalence was observed for both sexes with a characteristic predominance in females. The age-dependent seroconversion in females may be partly explained by additional infection from infected husbands to their wives but the reason for men remains obscure. The mean annual number of incident cases of ATLL was 11.4, giving 3.9 ATLL patients annually per 10(5) inhabitants, 6.1 per 10(5) inhabitants aged over 30, and 85.0 per 10(5) seropositives aged over 30. Crude annual incidence rate of ATLL among 10(5) male seropositives aged over 30 was 145.3 and that for females was 55.2 and 95% confidence intervals of ATLL incidence rates were 34.8 to 255.7 for males and 6.4 to 104.1 for females, respectively. Although the sex ratio of 80 ATLL patients was 1.35, males are more prone to the disease (46 male patients among 4,522 male seropositives aged over 30 vs 34 female patients among 8,801 female seropositives aged over 30; p less than 0.001) for unknown reason(s). Morbidity in male seropositives aged over 30 is 2.6 times as high as that of females. Decennial incidence rates in males in their fifties and sixties were significantly higher than those in females. The remarkable male preponderance in oncogenicity of HTLV-I may be due to the fact that men are more prone to the disease and the number of female carriers in the denominator used to calculate the incidence rate is larger than that of males. The whole life span (0-79) cumulative risk for males was 6.9% and significantly higher than that of females (2.95%).

Age Factors↗

[Evaluation of sialyl SSEA-1 antigen in patients with lung cancer].

Stage-specific embryonic antigen-1 (SLX) is a glycolipid recognized by a monoclonal antibody (FH 6) which is produced by cells immunized with mice teratocarcinoma cell line. Using an SLX (Otsuka) kit from Ostuka Assay Laboratory, we measured the serum level of SLX in 96 patients with lung cancer, 305 patients with non-cancerous lung disease and 86 healthy adults, prospectively. When we adopted a cutoff level of 42U/ml (mean + 2S.D. in the healthy adults), the overall positive rates were 29.2% in the lung cancer patients, 15.1% in the non-cancerous patients and 0% in the healthy adults. The positive rate of the lung cancer patients was significantly higher than in the patients with non-cancerous lung disease (p less than 0.05). According to the histological type of lung cancer, the positive rates were 40.9% in 44 patients with adenocarcinoma, 18.4% in 37 patients with squamous cell carcinoma, 0% in 7 patients with small cell carcinoma, and 0% in 3 patients with large cell carcinoma. Staging of the lung cancer patients revealed positive rates for serum SLX of 5.6% in 18 stage I patients, 22.2% in 9 stage II patients, 33.3% in 21 stage IIIA patients, 33.3% in 27 stage IIIB patients, 42.9% in 21 stage IV patients. After we performed the immunostaining method for SLX using FH6, positive immunoactivity was demonstrated mainly in the cell membrane of adenocarcinoma cells. SLX seems to be a tumor-associated marker in patients with lung adenocarcinoma.

Adenocarcinoma↗

Measurements of gaze movements while driving.

In this study, gaze movements of drivers driving through an intersection were investigated. Gaze movements of drivers in large vehicles were compared with those in small vehicles. There were both similarities and differences in the visual search behaviors of drivers of large and small vehicles. The two groups were similar in that, when approaching an intersection, drivers made repeated saccadic gaze movements; after entering the intersection, saccadic gaze movements were directed ahead in the direction of turning. Differences arose in the frequency and distribution of gaze movements. The number of gaze movements was significantly greater in drivers of large vehicles. The distribution of gaze movements in driving a large vehicle showed a peak at the point 50 to 60 degrees to the right and left of the median plane of the driver. The distribution of gaze movements of drivers of small vehicles showed no peak across the visual field.

Adult↗

[Mediastinitis and left pyopneumothorax complicating a laryngeal phlegmon].

A case of mediastinitis and left pyopneumothorax complicating a laryngeal phlegmon caused by Candida albicans is described. A 64-year-old woman was admitted complaining of pharyngeal pain, hoarseness, dysphagia, and pain behind the left angle of the mandible. In that hospital, she was diagnosed as having a laryngeal phlegmon. She was known to be diabetic and hypertensive since 54 years of age. After admission, she became dyspneic, and chest X-rays revealed left atelectasis, left pleural effusion and left pneumothorax. After a drain was inserted into the left thoracic cavity, she was transferred to our hospital. Chest X-rays showed widening of the mediastinum, an enlarged cardiac shadow, mediastinal emphysema, left pneumothorax and bilateral pleural effusion. A thoracic CT also showed extensive mediastinal emphysema. On March 19, 1988 we incised the abscess behind the left angle of the mandible and inserted drains into both the mediastinum and left thoracic cavity under general anesthesia. Candidiasis was diagnosed based on culture of pus obtained from the abscess behind the left angle of the mandible. She was treated with antibiotics intravenously and through both drainage tubes for about 1 month. She was cured and discharged after 5 months of hospitalization.

Candidiasis↗

[A case of giant leiomyoma of the esophagus].

A 34-year-old man was admitted to our hospital because of a tumor shadow in the posterior mediastinum. Leiomyoma of the esophagus was suggested by the findings of CT, esophagography, and esophagoscopy. He underwent thoracotomy. The operative procedure was enucleation of the tumor. The histological examination confirmed it to be a leiomyoma. The postoperative course was uneventful, and the passage of the esophagus was good. He was discharged 36 days after the operation.

Adult↗

[An experimental study on surgical treatment of tracheomalacia-- methods for making models of tracheomalacia and development of a new operative method].

To develop a new surgical method for the repair of tracheobronchomalacia, we conducted experiments on dogs. First, we created malacic models by fracturing or resecting 5 to 10 tracheal cartilages. The bearing strength of the tracheal lumen became remarkably weakened, and bronchoscopic examination revealed tracheal collapses during coughing. Second, we tried external stenting of the malacic tracheae with prostheses. In 11 dogs, a prosthesis composed of Silastic sheet and Marlex mesh was sutured to the malacic segments of trachea. The connective tissue around the prosthesis increased in amount and the tracheal wall became firmer with time. However, mucosal defects around the sutures were found in 4 of the dogs. Those defects were probably due to injury to capillaries by the suturing procedures. Therefore, instead of suturing, we decided to try adhesives for fixation of the prosthesis to the trachea. We tested three adhesives: PUP (polyurethane-prepolymer), cyanoacrylate and fibrin glue. In five dogs using cyanoacrylate, the tracheal walls were remarkably hardened within 3 to 8 months. In eight dogs using fibrin glue for fixation of Marlex mesh to the malacic trachea the results were satisfactory. With fibrin glue, the tracheal walls after 3 to 8 months had almost the same strength as the average of normal tracheae.

Animals↗

Beta-actinin: a capping protein at the pointed end of thin filaments in skeletal muscle.

We examined the function of beta-actinin as a pointed end capping protein of thin filaments in skeletal muscle. An improvement in preparing beta-actinin yielded purified beta-actinin which retained its activity for more than a week. Two-dimensional gel electrophoresis showed that the two subunits, beta I and beta II, of beta-actinin are, respectively, split into two to three components (isoforms) with different isoelectric points. Polyclonal antibody was raised by injecting such purified and undenatured chicken breast muscle beta-actinin composed of several components into a rabbit. Immuno-gold labeling examination with electron microscopy of an F-actin-beta-actinin complex decorated with HMM showed that 85% of bound gold particles was on the pointed end of actin filaments, while the remaining 15% was on the barbed end. This suggests that in beta-actinin preparation pointed end and barbed end capping proteins inevitably coexist. Immunofluorescence and immunoelectron microscopy directly showed that beta-actinin is located at the pointed end of thin filaments in myofibrils; it was also suggested that a capping protein having common antigenic determinants to beta-actinin is located at Z-line. Thus, the physiological function of beta-actinin as a pointed end capping protein was examined as follows: When beta-actinin was dissociated from the pointed end of thin filaments in an I-Z-I brush by using a high salt solution, thin filaments could be disassembled at the pointed ends at concentrations of exogenous actin lower than a critical value. At a physiological ionic strength, these salt-washed thin filaments gradually shortened at a constant rate of about 45 nm/h. Both the association and dissociation of monomeric actin at the pointed end were suppressed by the rebinding of exogenous beta-actinin. The main physiological role of beta-actinin is therefore to stabilize thin filaments in the sarcomere by preventing addition and removal of actin monomers at the pointed filament end.

Actin Cytoskeleton↗

Transition of beta-actinin isoforms during development of chicken skeletal muscle.

We examined by means of the immunoblotting technique the transition of beta-actinin isoforms during the development of the chicken from 5 day embryo to adult. As an antigen, beta-actinin was prepared from adult chicken breast muscle (pectoralis major) and polyclonal antibody was obtained by injecting undenatured beta-actinin into a rabbit. Immunoblotting examination of breast muscle at several stages of development (except 5 day embryo, in which the whole body minus the head and limbs was examined) showed that the species of beta-actinin subunits change during development: 1) beta I is already present in 5 day embryo, whereas beta II appears only after 9 days. 2) In 5 day embryo, we found, instead of beta II, a new subunit (designated beta III) that cross-reacts with the antibody, has the apparent molecular weight of 30,000 daltons and has a slightly alkaline isoelectric point compared with beta I. The content of beta III gradually decreased and beta III completely disappeared a week after hatching. Such a type of transition of the isoforms in beta-actinin subunits is similar to that observed in other muscle proteins. The transition of beta-actinin isoforms may correlate to the organization of an I-Z-I brush, especially to the length determination of thin filaments, because the developmental stage at which beta III disappears coincides with that at which the length of thin filaments is strictly determined.

Actinin↗

Beta-actinin isoforms in various types of muscle and non-muscle tissues.

We found that beta-actinin isoforms are present in various types of tissues in adult chicken by using immunoblotting after two dimensional gel electrophoresis; for this purpose, an antibody was raised against beta-actinin purified from adult chicken breast muscle (pectoralis major). One of the beta-actinin subunits, beta I, was present in all tissues we examined, i.e. skeletal (pectoralis major, semitendinosus, and anterior latissimus dorsi), cardiac, and smooth (gizzard) muscles, non-muscle (brain, liver, and kidney) tissues and blood, whereas another subunit, beta II, was present only in muscle tissues. A new subunit (designated beta III) that was found in the embryonic stages of skeletal muscle (Asami, Funatsu & Ishiwata (1988) J. Biochem. 103, 72-75) was present instead of beta II in non-muscle tissues and blood. In cardiac and smooth muscles, beta III coexisted with beta I and beta II. The antibody of beta-actinin did not cross-react to cytoplasmic beta-actinin (molecular weight, 80,000 daltons) found in kidney. It was suggested that the combination of beta I and beta III present in non-muscle tissues and blood is identical to the barbed end capping protein isolated from brain by Killiman and Isenberg (EMBO J. 1, 889-894 (1982)). It is likely that beta-actinin forms a genetic family whose constituents have an ability to cap either the pointed or barbed end of actin filaments.

Actinin↗

Beta-actinin is not distinguishable from an actin barbed-end capping protein in chicken breast muscle.

beta-Actinin is an actin-pointed end capping protein in skeletal muscle. Casella et al. have reported that a protein isolated from muscle acetone powder by procedures similar to those used for beta-actinin purification caps the barbed end of an actin filament (J. Biol. Chem. 261, 10915-10921 (1986)). We have confirmed the above results. However, it turned out that the two proteins were identical as to subunit sizes, peptide maps, and cross-reactivities with anti-beta-actinin IgG. The binding of the two proteins to opposite ends of an actin filament remains unexplained.

Actin Depolymerizing Factors↗

[Prosthetic reconstruction of the trachea and carina].

We have performed prosthetic reconstruction of the trachea and carina in 12 patients since 1979. We used Neville's prosthesis in 7 patients and Katsura's prosthesis in 5 patients. Seven patients were operated on for lung cancer, 2 patients for adenoid cystic carcinoma of the trachea and the others for large cell carcinoma of the trachea, thyroid cancer and tuberculous granuloma, respectively. Prosthetic reconstruction of the trachea was performed in 4 patients. Carinal resection was performed in 8 patients: With right sleeve pneumonectomy in 4 patients, with right upper lobectomy in 2 patients and only carinal resection in 2 patients. Prosthetic reconstruction after the carinal resection was performed using 3 straight types, 1 curved type and 4 bifurcated types. With regard to the complications of the prosthetic reconstruction, dehiscence at the anastomotic site was seen in 5 patients, granulation in 4 patients, empyema in 3 patients, massive hemorrhage in 2 patients and migration of the prosthesis in 1 patient. Five patients survived more than 1 year. The longest survival time was 43 months. To prevent complications of the prosthetic reconstruction, we improved the anastomotic method, reinforced the anastomotic site with Marlex mesh and protected the surrounding vessels with Lyodura.

Adult↗