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Biomedical subjects

M Ohata

Publications and source records attributed to M Ohata.

At least 19 recordsLinked to original sources

Increased phosphorylation of nuclear phosphoproteins in human lung-cancer cells resistant to cis-diamminedichloroplatinum (II).

A novel non-phorbol-ester-like tumor promoter, okadaic acid (OA) has been shown to be an inhibitor of protein phosphatase I and IIA and, thus, to cause an "apparent activation" of protein kinase C (PKC). We previously showed that cis-diamminedichloroplatinum(II) (CDDP)-resistant cells, PC-9/CDDP, were cross-resistant to OA and that the cross-resistance was not due to the increased efflux of OA. We hypothesized that the phosphorylation status of some cellular proteins might be important in CDDP-resistance. No significant difference in PKC activity or total protein phosphatase activity measured in vitro was seen between PC-9 and PC-9/CDDP cells, nor in their sensitivity to inhibition by OA, nor in the amount of phosphorylation of whole cells or TCA-insoluble material. By SDS-PAGE after incubation of intact cells with 32P, we detected a marked increase, compared to PC-9 cells, in phosphorylation of the nuclear proteins of MW 32 and 20 kDa in CDDP-resistant PC-9/CDDP cells with no apparent difference in protein content. When phosphorylation of nuclear proteins observed in PC-9/CDDP cells was analyzed by 2-dimensional SDS-PAGE, the 32-kDa protein had a PI of about 4.5. The 32-kDa and 20-kDa bands were increased in a dose-dependent manner by CDDP treatment. On the other hand, no increase in phosphorylation of these proteins was observed in parental PC-9 cells. These results demonstrate a marked difference in the phosphorylation status of specific nuclear proteins between parental and CDDP-resistant cell lines, which may be related to CDDP-resistance.

Adenocarcinoma

Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by cis-diamminedichloroplatinum(II).

We have investigated the effect of cis-diamminedichloroplatinum(II) (CDDP) on signal transduction pathways. CDDP treatment did not cause any change in the binding of [3H]-phorbol dibutyrate to PC-9 (human lung adenocarcinoma cell line) cells, a measure of protein kinase C activation. However, 2-h CDDP treatment (20 micrograms/ml) caused approximately 200% increase in 1,2-sn-diacylglycerol (DAG) production and approximately 50% decrease in inositol 1,4,5-triphosphate production. To explore the different source of DAG, we analyzed phospholipids labeled with [14C]choline by TLC and revealed that [14C]choline-labeled phosphatidylcholine (PC) was decreased to 50% by CDDP treatment. This suggested that PC turnover was increased by CDDP-treatment. PC-specific phospholipase C (PC-PLC) activity was increased to 2.5-fold (2.58 +/- 0.28 nmol/mg protein per min) by 2 h CDDP (20 micrograms/ml) treatment compared with control (1.05 +/- 0.24 nmol/mg protein per min). Treatment of CDDP also stimulated PC-PLC in the crude membrane extract from PC-9 cells. CDDP had no effect on the activities of phospholipase A2 and D. Trans-DDP, which has far less cytotoxicity than its stereoisomer, CDDP, did not cause any change in PC-PLC activity. A significant inhibition of DNA synthesis (less than 80%) occurred 4 h after 2 h CDDP (20 micrograms/ml) treatment. These results demonstrated that CDDP-induced PC-PLC activation was an early event in CDDP-induced cytotoxicity and suggested that the effects of CDDP on signal transduction pathways had an important role in CDDP-induced cytotoxicity.

Cisplatin

Idiopathic acute eosinophilic pneumonia.

A previously healthy young man presented with acute respiratory distress, high fever and bilateral ground-glass appearance on chest radiograph. Bronchoalveolar lavage analysis demonstrated significant eosinophilia (72%) with no evidence of infection. The transbronchial lung biopsy showed that the walls of bronchioli and alveolar septa were markedly infiltrated with eosinophils. The patient rapidly improved with corticosteroid therapy. This case exemplifies the recently described idiopathic acute eosinophilic pneumonia. Similar cases published in the Japanese literature were reviewed and discussed.

Acute Disease

[A clinical and ultrastructural study of Fechtner syndrome in two Japanese families].

This is a report of Fechtner syndrome in two Japanese families. Six members of family I and three members of family II were studied. All but one had macrothrombocytopenia and leukocyte inclusion bodies, four had deafness, four had persistent proteinuria and none had cataracts. Under a diagnosis of ITP, two of them had splenectomy which resulted in no response. History revealed, other family members with deafness and/or nephritis were confirmed in both families. Ultrastructural studies of leukocytes showed oval inclusion bodies with unclear borders containing many fine ribosome like granules and randomly scattered filaments. Ultrastructural studies of macrothrombocytes were unremarkable except for a well-developed open canalicular system. More than half of megakaryocytes had uneven basophilic speckles in the cytoplasm, which were positive for Unna-Pappenheim staining. Ultrastructurally, widening of demarcating systems and remaining ribosomes were noted in the cytoplasma of mature megakaryocytes.

Deafness

[A case of Wegener's granulomatosis complicated by hypopituitarism].

A 71-year-old male complaining of chest pain was admitted to our hospital. A single cavitary mass shadow was observed on chest X-ray films. Urinalysis revealed microscopic hematuria. CT examination demonstrated a tumorous shadow in the maxillary sinus. The diagnosis of Wegener's granulomatosis was histologically established by biopsy specimens from the nasal mucosa which showed necrotizing vasculitis and granuloma with fibrinoid degeneration. He was treated with combination therapy of prednisolone and cyclophosphamide. The abnormal shadows on chest X-ray and in the maxillary sinus on CT improved rapidly, but the patient developed progressive weight loss and complained of cold intolerance, weakness and dysphagia. Serum T3, T4 and TSH were found to be reduced. Anterior pituitary function tests showed reduction of TSH, GH and ACTH responses, which was probably due to irreversible vasculitis.

Aged

[Treatment of pericardial cyst under thoracoscopy].

Thoracoscopic therapy was carried out on two cases of pericardial cyst. The first patient was a 24-year-old male. An abnormal shadow on a chest X-ray was pointed out at a regular checkup. Thoracoscopy was carried out under the local anesthesia and a thin-walled cyst was discovered. The cyst was punctured and serous fluid was aspirated. Then, several biopsy specimens were obtained from the cyst wall, a pathological diagnosis of the cyst was made as a pericardial cyst. One year after the thoracoscopy, no abnormal shadow is observed on chest X-ray. The second patient was a 26-year-old male. It was also discovered that he had an abnormal shadow on a chest X-ray at a regular medical checkup. Since a solid mass couldn't be completely denied, thoracoscopy was carried out in preparing for thoracotomy under the general anesthesia. The cyst observed between SVC and the azygos vein, and serous fluid was aspirated form the cyst. Following this, the cyst wall was biopsied and opened. Since no cases of malignant pericardial cysts have been reported, an operation is not usually required for these patients. We suggest that thoracoscopy is very useful tool for the final diagnosis and therapy of pericardial cyst because this method is easily carried out under local anesthesia.

Adult

[Long-term patency of aorto-coronary saphenous vein grafts].

One hundred eighty-two cases with 814 aorto-coronary saphenous vein grafts were studied according to coronary risk factors (smoking, hypertension, hyperlipidemia, diabetes mellitus, obesity and family history). The patency rates of all cases were as follows, early-term (within one year after operation): 92.3%, mid-term (within 5 years after operation) 80.7%, long-term (more than 5 years after operation): 66.0%. Coronary risk factors have great influence upon the mid- and long-term patency, especially upon the latter. The long-term patency rate of the grafts complicated with hyperlipidemia was 57.4% and that without hyperlipidemia was 81.8% (p less than 0.01). Hyperlipidemia, complicating 55.5% of all cases, was one of the most influential factors on the patency and also the most difficult one to be controlled. In the United States and Europe, many cases were complicated with hyperlipidemia, and it was considered that the poor patency of the saphenous vein grafts in those countries was due to this fact. Pathological studies revealed that hyperplasia of intima and media, characteristics of venosclerosis, appeared frequently in the saphenous vein grafts having more than three risk factors, and that the factors had effect not only upon arteries but also upon veins. So we conclude that saphenous vein grafts are the materials of good long-term patency, and that the control of the risk factors, particularly hyperlipidemia, is the key to improve the patency.

Adolescent

[Regeneration of the respiratory epithelium].

It is very important to clarify the mechanism of the regeneration of the respiratory epithelium in not only Oto-Naso-Laryngology but also in the field of chest medicine and surgery. Because of the experimental study carried out on dogs, involving the curing process of the tracheal anastomosis site, a scanning electron microscopic study showed that after two weeks, ciliated cells could be seen making a thin layer. It took nine weeks or more till the whole tracheal anastomosis site was completely covered by the ciliated epithelial cells. Having reviewed the experimental papers concerning the regeneration of the respiratory epithelium which have been published since 1953, a conclusion has been reached that after the injury of the respiratory mucosa, the existence of the basement membranes remains were covered by the migration of the traditional epithelium from the margin of the wound and four weeks later, the wound was covered by the normal epithelium. It has been stated up until now that the differentiation of the epithelium was covered from basement cells, but in fact, it seems to occur from the secretory cells. This has been demonstrated by the culture process of the respiratory epithelium. From these facts, the cultured respiratory epithelium cells are very important in elucidating carcinogenesis.

Animals

Detection of fibronectin receptor in sera: its clinical significance as a parameter of hepatic fibrosis.

Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.

Adult

[Trans-sternal bilateral thoracotomy for bilateral lung lesions].

The trans-sternal bilateral thoracotomy had been used widely in the early days of cardiac surgery, but since the 1960's the median sternotomy has played a great part in open heart surgery. Recently, the simultaneous bilateral thoracotomy has been used for bilateral lung lesions such as bilateral giant bullae, bilateral pneumothoraces and bilateral metastatic lung tumors. Since 1965 we have performed 6 operations using trans-sternal bilateral thoracotomy for several bilateral lung lesions. The diseases which led to the use of the trans-sternal bilateral thoracotomy technique were 2 cases of bilateral simultaneous pneumothoraces and 4 cases of bilateral lung metastatic tumors. The ages of the patients ranged from 17 to 45 years old. The operative blood loss was between 100 and 810 gm. No case showed postoperative respiratory distress or severe thoracic pain. It would like to be pointed out that the trans-sternal bilateral thoracotomy is the most ideal approach for the multiple bilateral lung metastatic lesions which often invade the chest wall or diaphragm.

Adolescent

[An evaluation of surgical treatment for giant bullae].

We have experienced 67 operative cases of giant emphysematous bullae of the lung. For the bilateral lesions, two stage operation was performed in five cases and one stage operation under median-sternotomy in 12 cases. Twenty six cases were subjected to Naclerio-Langer's method, 25 cases to partial resection or plication and 15 cases to lobectomy. At the earlier period lobectomy was the treatment of choice, but, recently lobectomy was avoided for the conservation of pulmonary function. In terms of the improvement of pulmonary function, there was no difference between Naclerio-Langer's method and partial resection by Autosuture. In conclusion, for the treatment of giant bullae, partial resection by Autosuture is preferable because of improvement of pulmonary function and one stage median-sternotomy for bilateral lesions also are effective.

Adult

[Establishment and characterization of a new human germ cell tumor strain (NOC-Ts) in culture].

We have derived and characterized a new cell line from a teratoma with a embryonal carcinoma and seminoma. The medium used for the cell culture was Eagle's MEM synthetic culture medium (Gibco Inc.) supplemented with 10% new calf serum (Tissue plus, Mitsubishi Kasei Co.). Subcultures were performed on 3 to 4 days basis at 1:2 split by the use of 0.25% trypsin solution. The morphology of obtained cells was a epithelial-like shape and the cell grew in a monolayered sheet with about 30-32 hrs of population doubling time. The model chromosome number of this cell line was 73 including one large submetacentric marker chromosome. The temperature sensitivity and the tumorigenicity of this cell were tested in this experiment.

Adult

[A case of cystic hygroma of the chest wall].

Hygroma is generally regarded as a benign tumor occurring favoritely in the cervical region of a child. Recently we have experienced a case of hygroma which was initially detected as a right chest wall tumor in a 16-year-old man, then was surgically diagnosed as cystic hygroma; chest roentgenography on a check up examination in his senior high school pointed out some anomaly, leading to his hospitalization. On admission, he had no subjective symptom, but chest roentgenography and CT confirmed an abnormal shadow in the right pulmonary area and a tumor with calcification on the right chest wall, respectively, so he was operated on for excisional biopsy. The tumor was extirpated together with the 7th intercostal muscle adhered to the tumor, and postoperative pathohistological examination led to diagnosis as cystic hygroma. Cystic hygroma of the chest wall is so rare that we would like to report this case, together with some addition consideration of related literature.

Adolescent

[A case of primary intrapulmonary benign schwannoma].

A case of primary intrapulmonary schwannoma was described. A 72-year-old man was admitted to our hospital because of dry cough. A chest radiograph showed partial atelectasis of the middle lobe, but computed tomogram of the chest revealed no tumor shadow. Bronchoscopy disclosed a pale-yellow uneven endobronchial wall of the right middle lobe bronchus. Transbronchial biopsy revealed benign schwannoma. Primary intrapulmonary schwannoma has been rarely reported.

Aged

[Establishment and characterization of human cancer cell line (NOC-S) derived from a progressive lung cancer].

The results of the transplantation out of a progressive lung cancer tissue with leukocytosis showed that tumors were grown in nude mice at about 70 days after direct transplantation. A tumor was removed from the nude mouse for attempt at establishment of cell line in vitro. The medium used for the cell culture was MEM synthetic culture medium (Gibco Inc.) supplemented with 10% new borne bovine serum. Subcultures were performed on 5 to 6 days basis at 1:2 split by the use of 0.25% trypsin solution. The morphology of obtained cells was a spindle-like shape and the cell grew in a monolayered sheet with about 32 to 36 hr of population-doubling time. The modal chromosome number of this cell line was 44 including one large submetacentric and one minute marker chromosome. Cell lines were tested for tumorigenicity with an inoculum of five million cells in nude mice. This cell lines produced tumors with high rate. The tumor has been maintained in nude mice through serial passages over a period of one year. The temperature sensitivity and the colony stimulating factor-producing of this cells will be discussed.

Adenocarcinoma

[A case of thymolipoma on the cervicomediastinal area].

Thymolipoma is a very rare mediastinal tumor. We reported a case of 52-year-old female with thymolipoma which was located in the cervicomediastinal area. The chest X-ray film revealed an abnormal shadow in the superior mediastinum. Computed Tomography (CT) clearly showed the existence of a large mass in the left side of the trachea. The angiogram showed that there was a stenosis on the left brachiocephalic vein. On June 13, 1988, median sternotomy was performed. A large tumor, about 5.5 x 13 x 5.5 cm, was found arising from the left cervical area. This tumor was excised completely and thymolipoma was diagnosed histopathologically. The post-operative course was very satisfactory.

Female

[Serum adenosine deaminase and its isozyme activity in leukemia and MDS].

We studied the activity of serum adenosine deaminase (ADA) and its isozyme in 36 leukemic patients (16 ANLL, 11 ALL, and 9 CML) and 8 MDS. Isozyme was measured by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibitory assay. This assay was simple and reliable. The appearance rate of abnormally high ADA value were 81.24% for ANLL, 100% for ALL, 77.8% for CML and 37.5% for MDS. The ADA level became high when MDS turned into overt leukemia. In isozyme pattern, there was a clear difference between ANLL and ALL. The isozyme I/II ratio was significantly higher (p less than 0.001) in ALL than ANLL. Lymphoblastic crisis of CML also had a high isozyme I/II ratio. There was a correlation between isozyme I and absolute number of peripheral blasts in ALL (r = 0.768). When observed time sequentially, ADA and isozyme changed correlatively with the number of blasts counts. Serum ADA and its isozyme are useful parameters both for leukemic diagnosis and treatment.

Adenosine Deaminase

Electron microscope study on the bat testicular interstitial cell with special reference to the cytoplasmic crystalloid.

The testicular interstitial cell of the bat, Myotis schreibersi (Temmink), captured late in August was electron microscopically investigated. The cytoplasm of Myotis interstitial cells is packed by strikingly numerous mitochondria with many electron dense small matrix granules, endoplasmic reticulum and variable numbers of osmiophilic lipid droplets. The Myotis interstitial cell is characterized by alternate development of the SER and RER: In some Leydig cells the major part of the cytoplasm is packed by tubular SER, whereas in others this apparently is replaced by abundant free ribosomes containing sparse cisternae of the RER. These changes in the amounts of ser and RER are likely reversible and probably reflect functional alterations of Leydig cells of the bat, a hibernator. The Myotis interstitial cell possesses small cytoplasmic crystalloids composed of regularly oriented, compressed tubules, 20-28 m mu thick, which are continuous to the tubular SER (SER derived crystalloids). Type I and type II crystalloids are classified, which show, in suitable planes of section, honeycomb-like and fabric-like patterns, respectively. The Myotis Leydig cell extends cytoplasmic processes of irregular shape and long microvilli, the latter often conglomerates on the cell body or cytoplasmic processes. The entire surface of the cell including the processes is completely surrounded by a basal lamina.

Animals