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Biomedical subjects

A Masaoka

Publications and source records attributed to A Masaoka.

At least 19 recordsLinked to original sources
PubMed1999

Enzymatic repair of 5-formyluracil. I. Excision of 5-formyluracil site-specifically incorporated into oligonucleotide substrates by alka protein (Escherichia coli 3-methyladenine DNA glycosylase II).

5-Formyluracil (fU) is a major thymine lesion produced by reactive oxygen radicals and photosensitized oxidation. We have previously shown that fU is a potentially mutagenic lesion due to its elevated frequency to mispair with guanine. Therefore, fU can exist in DNA as a correctly paired fU:A form or an incorrectly paired fU:G form. In this work, fU was site-specifically incorporated opposite A in oligonucleotide substrates to delineate the cellular repair mechanism of fU paired with A. The repair activity for fU was induced in Escherichia coli upon exposure to N-methyl-N'-nitro-N-nitrosoguanidine, and the induction was dependent on the alkA gene, suggesting that AlkA (3-methyladenine DNA glycosylase II) was responsible for the observed activity. Activity assay and determination of kinetic parameters using purified AlkA and defined oligonucleotide substrates containing fU, 5-hydroxymethyluracil (hU), or 7-methylguanine (7mG) revealed that fU was recognized by AlkA with an efficiency comparable to that of 7mG, a good substrate for AlkA, whereas hU, another major thymine methyl oxidation products, was not a substrate. (1)H and (13)C NMR chemical shifts of 5-formyl-2'-deoxyuridine indicated that the 5-formyl group caused base C-6 and sugar C-1' to be electron deficient, which was shown to result in destabilization of the N-glycosidic bond. These features are common in other good substrates for AlkA and are suggested to play key roles in the differential recognition of fU, hU, and intact thymine. Three mammalian repair enzymes for alkylated and oxidized bases cloned so far (MPG, Nth1, and OGG1) did not recognize fU, implying that the mammalian repair activity for fU resided on a yet unidentified protein. In the accompanying paper (Terato, H., Masaoka, A., Kobayashi, M., Fukushima, S., Ohyama, Y., Yoshida, M., and Ide, H., J. Biol. Chem. 274, 25144-25150), possible repair mechanisms for fU mispaired with G are reported.

Adenine↗
PubMed1999

Enzymatic repair of 5-formyluracil. II. Mismatch formation between 5-formyluracil and guanine during dna replication and its recognition by two proteins involved in base excision repair (AlkA) and mismatch repair (MutS).

5-Formyluracil (fU), a major methyl oxidation product of thymine, forms correct (fU:A) and incorrect (fU:G) base pairs during DNA replication. In the accompanying paper (Masaoka, A., Terato, H., Kobayashi, M., Honsho, A., Ohyama, Y., and Ide, H. (1999) J. Biol. Chem. 274, 25136-25143), it has been shown that fU correctly paired with A is recognized by AlkA protein (Escherichia coli 3-methyladenine DNA glycosylase II). In the present work, mispairing frequency of fU with G and cellular repair protein that specifically recognized fU:G mispairs were studied using defined oligonucleotide substrates. Mispairing frequency of fU was determined by incorporation of 2'-deoxyribonucleoside 5'-triphosphate of fU opposite template G using DNA polymerase I Klenow fragment deficient in 3'-5' exonuclease. Mispairing frequency of fU was dependent on the nearest neighbor base pair in the primer terminus and 2-12 times higher than that of thymine at pH 7.8 and 2.6-6.7 times higher at pH 9.0 with an exception of the nearest neighbor T(template):A(primer). AlkA catalyzed the excision of fU placed opposite G, as well as A, and the excision efficiencies of fU for fU:G and fU:A pairs were comparable. In addition, MutS protein involved in methyl-directed mismatch repair also recognized fU:G mispairs and bound them with an efficiency comparable to T:G mispairs, but it did not recognize fU:A pairs. Prior complex formation between MutS and a heteroduplex containing an fU:G mispair inhibited the activity of AlkA to fU. These results suggest that fU present in DNA can be restored by two independent repair pathways, i.e. the base excision repair pathway initiated by AlkA and the methyl-directed mismatch repair pathway initiated by MutS. Biological relevance of the present results is discussed in light of DNA replication and repair in cells.

Adenine↗
PubMed1999

Thymic neuroendocrine tumor (thymic carcinoid): a clinicopathologic study in 15 patients.

BACKGROUND: Thymic neuroendocrine tumor (carcinoid tumor) is rare, and prognosis for patients with this tumor has been difficult to predict. METHODS: The medical records of 15 patients were reviewed, and the patients were classified according to tentative TNM classification and histologic grade. RESULTS: Ten (66.7%) of 15 patients were male. Lymph node metastases were identified in 9 (60%) of 15 patients at the time of resection. There were one grade 1, nine grade 2, and five grade 3 tumors. Total resection was possible in 13 patients. Distant metastases developed in 10 (76.9%) of these 13 patients, although no local recurrence developed. Of these 10 patients, 6 died of distant metastases 5 to 25 months after the recurrence. Three patients are still alive, with metastases to the bone, spleen, and pleura 1 to 24 months after the diagnosis of recurrence. Two patients are presently tumor free (T1N0, grade 3 and T3N2, grade 2), but only 1 has survived beyond 5 years. CONCLUSIONS: Thymic neuroendocrine tumor must be regarded as a malignant neoplasm that is prone to metastasize to mediastinal lymph nodes and to distant sites, even after total excision. Neither T and N classification nor histologic grade has been successful in predicting the outcome of a patient with this tumor. More aggressive management, including adjuvant therapies and reexcision of subsequent tumors, may result in increased survival.

Adult↗
PubMed1999

Cellular repair mechanism of 5-formyluracil.

5-Formyluracil (fU) is an oxidative DNA base damage. This damage has been suggested to be mutagenic and but enzymatic repair of the damage is little known. In this study, repair enzymes that recognize fU have been studied. Kinetic analysis of the repair activity of E. coli 3-methyladenine DNA glycosylase II (AlkA) showed that fU was removed by AlkA with the efficiency comparable to 7-methylguanine. We also examined the participation of the methyl-directed mismatch repair system. The affinity of MutS to the fU:G mispair was essentially similar to that of the T:G mispair that was most efficiently recognized by the MutSLH system. These results suggest two distinct repair pathways of fU in E. coli.

Base Pair Mismatch↗
PubMed1997

Thymic follicular hyperplasia manifested as an anterior mediastinal mass.

A rare case of thymic follicular hyperplasia manifested as an asymptomatic anterior mediastinal mass in a 44-year-old man is herein reported. The resected thymus showed prominent medullary lymphoid follicles, an increased number of Hassall's corpuscles, and cysts of varying sizes. This paper discusses the histopathological condition of this lesion.

Adult↗
PubMed1997

Chondrosarcoma originating from the trachea.

We report a tracheal chondrosarcoma in a 54-year-old man, treated with neodymium:yttrium-aluminum garnet laser vaporization via fiberoptic bronchoscopy followed by surgical resection. Chondrosarcomas of the trachea are extremely rare tumors. To our knowledge, there are 9 cases of chondrosarcoma of the trachea reported in the English-language literature, to which we add the tenth.

Biopsy↗
PubMed1997

Experimental reconstruction of the mediastinal trachea with a wing-shaped reversed esophageal flap.

BACKGROUND: In cases of extensive tracheal resection in which direct end-to-end anastomosis is impossible there is a need for reconstruction. Nevertheless, with the present lack of reliable artificial trachea, no reconstruction method is available to assure safe replacement of the mediastinal trachea. METHODS: After tubular resection of the mediastinal trachea in mongrel dogs, the trachea was reconstructed using a wing-shaped reversed esophageal flap. A silicone tube was used as an internal stent. RESULTS: In group I (16 animals), three tracheal rings were resected; in group II (4 animals), six tracheal rings; in group III (6 animals), eight tracheal rings; and in group IV (5 animals), eight tracheal rings and the lining of the greater omentum. Safe reconstruction was accomplished in all cases in groups I and II, 2 of 6 cases in group III, and 2 of 5 cases in group IV. The omentopexy failed to prevent incomplete closure, yet served to minimize inflammation in the mediastinum. CONCLUSIONS: A reversed esophageal autograft can be considered as a tracheal replacement.

Animals↗
PubMed1997

Elevated plasma thymosin-alpha1 levels in lung cancer patients.

OBJECTIVE: Prothymosin-alpha, the precursor of thymosin-alpha1, may play a role in cell proliferation, and the plasma level of thymosin-alpha1 may reflect the degree of proliferation of the tumor cells. METHODS: Recently, a new sandwich immunoradiometric assay for thymosin-alpha1 was developed using monoclonal and polyclonal antibodies. In this investigation, we used this assay to measure plasma and tissue level of thymosin-alpha1 in 131 lung cancer patients. RESULTS: We found that the mean plasma thymosin-alpha1 levels in lung cancer patients were higher than in normal individuals (P < 0.001). However, half of the patients showed normal levels. Thymosin-alpha1 levels correlated neither with the stage nor pathological subtype of the lung cancer, and did not decrease significantly in the 4 weeks after the resection of the tumor. Thymosin-alpha1 levels of lung cancer patients with another cancer were higher than those without evidence of other cancers (P = 0.03). Survival of patients with normal levels of plasma thymosin-alpha1 was significantly better than that with higher levels (P = 0.04). CONCLUSIONS: The plasma level of thymosin-alpha1 may be used as a marker for the prognosis of lung cancer patients. Further investigations are warranted to determine its role in the lung cancer.

Adenocarcinoma↗
PubMed1997

Clinical significance of bcl-2 gene expression in human breast cancer tissues.

The expression of estrogen receptor (ER) and bcl-2 (Bcl-2), an apoptosis protective oncogene, in normal and cancerous breast duct epithelia was immunohistochemically examined in fresh frozen tumor tissues from 142 Japanese breast cancer patients. The clinico-pathological characteristics and the disease free survival of the patients were analyzed. The expression of both the proteins was also observed in intraductal components of breast cancer. Although less than 1% of normal duct epithelia expressed ER, Bcl-2 was diffusely expressed. The expression of both these proteins in breast cancer significantly correlated with each other. Their expression significantly correlated negatively with tumor size but not with lymph node status. The papillo-tubular sub-type of invasive ductal carcinoma expressed Bcl-2 significantly more frequently than the solid-tubular sub-type. Patients with Bcl-2 expressing tumors survived without recurrence significantly more than those with tumors exhibiting reduced expression. Papillary-cribriform type intraductal components expressed both those proteins more often than the solid-comedo type.

Adult↗
PubMed1997

[Intrapulmonary laceration revealed by computed tomography in a patient with pneumomediastinum].

An 18-year-old man had bronchial asthma and a pneumomediastinum. A computed tomographic scan of the chest revealed the pneumomediastinum, intrapulmonary laceration of the S1b, and a small amount of air in the perivascular space from V1a to V1. Increased pressure in intrapulmonary airways may have resulted in ruptured S1b alveoli and air leakage into the interstitium between the surrounding secondary lobules. The air may have moved along the perivascular space (pulmonary vein) toward the hilum, and eventually into the mediastinum. We know of no previous report of pneumomediastinum in which images of intrapulmonary lesions are presented. In this case computed tomography revealed the mechanism by which the pneumomediastinum probably developed.

Adolescent↗
PubMed1997

[TNM classification of thymic epithelial tumors].

The five-stage classification system of thymoma (I, II, III, IVa, IVb) is now adopted widely. As the cases with lymphogenous or hematogenous metastasis are included in IVb, it is suggested that IV b includes various groups with different prognostic factors. This facilitates establishment of TNM classification of thymic epithelial tumours (thymoma, thymic cancer and thymic carcinoid). T factors correspond with the stages, I: T1N0M0, II: T2N0M0, III: T3N0M0, and IV a : T4 N0M0. N and M factors are as follows: N1 : restricted to the anterior mediastinal nodes; N2 : intrathoracic nodes; N3 : supraclavicular nodes; and M1 : hematogenous metastasis and/or extrathoracic nodes excluding supraclavicular nodes. Such criteria were used to classify IVb into any T N(1,2,3) M0, and any T any NM1. N criteria could divide the cases into the groups with proper populations in IV b thymoma, thymic carcinoma, and thymic carcinoid, respectively. The possible relationships between survival and TNM were investigated in thymic carcinoma cases. T, N, and M have a relationship with survival, respectively. This TNM classification is not yet authorized, but it is used in many clinics in Japan to determine the selection of therapy and estimate the therapeutic effect.

Carcinoid Tumor↗
PubMed1997

Mechanisms of the genotoxic effects associated with 5-formyluracil: effect of exogenous 5'-formyl-2'-deoxyuridine.

E. coli HB101 harboring plasmid pUC19 was grown in the presence of 5-formyl-2'-deoxyuridine (fdU) to evaluate the genotoxic and cytotoxic potentials associated with this DNA lesion. Cell growth was inhibited by fdU in a concentration-dependent manner, but increased mutation was not observed in the lacZ(alpha) gene of pUC19. The lack of the mutagenic effect was attributed to poor utilization of fdU as a substrate by thymidine kinase, which converts exogenous thymidine analogs to the corresponding 5'-monophosphates in the salvage pathway.

Cell Division↗
PubMed1996

Flow Cytometric Assay of c-erbB-2 Protein in Fine Needle Aspirates of Fresh and Frozen Human Breast Cancer Tissues.

Using FCM (flow cytometry), we analyzed the ErbB-2 (c-erbB-2 protein) status of 61 breast cancer tissue samples obtained by FNAB (fine-needle aspiration biopsy). The number of cancer cells collected by FNAB from fresh samples was 1.7+/-0.7 x10&sup5;, 2.5 +/-0.6 x10&sup5;, and 4.0+/- 0.8x10 &sup5;, by single, double and triple aspirations, respectively. A mean of 3.0+/-0.6 x10&sup5;cells was collected on three aspirations from frozen samples. The number of cells collected on three aspirations was sufficient for the measurement of ErbB-2. Cells with higher ErbB-2 levels than those of normal human lymphocytes were designated ErbB-2 positive cells. The mean overall for ErbB-2 positive cell rates was 20.5 +/- 27.9 % (mean+/-SD). The rates were 27.9 +/- 31.6 % in patients with recurrence and 15.9 +/- 24.4% in patients without recurrence. When the cut-off value was set at 20% of the positive cell rate (P =0.008, generalized Wilcoxon test), patients with ErbB-2 negative tumors showed highly significantly longer survival without recurrence (P=0.008, generalized Wilcoxontest) and better overall survival rates (P=0.013) than patients with ErbB-2 positive tumors. Among 61 specimens, 16 (26.2%) scored positive for ErbB-2 by FCM. These finding indicated that the analysis of ErbB-2 status using FCM of samples obtained by FNAB should be useful for preoperatively evaluating the prognosis of patients with breast cancer.

Journal Article↗
PubMed1996

Ischemic injury of the small intestine studied by 31P-MRS.

In order to examine the efficacy of phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS) of the small intestine during superior mesenteric artery occlusion (SMAO) and reperfusion, we compared the beta-ATP level measured by in vivo 31P-MRS and the ATP level measured by high performance liquid chromatography (HPLC) in a rat model. The rat small intestines were subjected to 30 or 90 min of SMAO followed by reperfusion. 31P-nuclear magnetic resonance spectra were taken every 10 min during SMAO and subsequent reperfusion. Specimens for HPLC were taken every 30 min. Metabolite levels measured by 31P-MRS and HPLC demonstrated a linear correlation. This result shows that 31P-MRS can determine the ATP content of the small intestine as well as HPLC. Additionally, the changes of beta-ATP, inorganic phosphate (Pi) and tissue pH in the small intestine during SMAO and reperfusion were examined by 31P-MRS in detail. beta-ATP decreased with longer SMAO times, and the recovery rate of beta-ATP after reperfusion also decreased with longer SMAO times. Therefore, the ATP level measured by 31P-MRS may provide a clinical parameter of tissue damage and organ viability. The levels of Pi and tissue pH changed greatly, but reached a plateau in the early phase of SMAO. Their levels after reperfusion reflected the time of SMAO, and therefore may also provide a clinical parameter of organ viability.

Adenosine Triphosphate↗
PubMed1996

Extended thymectomy for myasthenia gravis patients: a 20-year review.

BACKGROUND: Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated. METHODS: Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point. RESULTS: Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome. CONCLUSIONS: Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Adult↗
PubMed1996

Esophageal tracheobronchoplasty for diseases of the central airway.

Three infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis (n = 4), repair of the defect (n = 1), or both (n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging.

Adult↗
PubMed1996

Pediatric and adult tracheobronchomalacia.

Twelve cases of tracheobronchomalacia (TBM) cases were reviewed: five were pediatric, and seven were adult, two of which were due to relapsing polychondritis (RPC). In pediatric TBM, the malacic segments were short. Resection of the malacic segment in one case and laryngotracheoplasty with autologous costal cartilage in one case were unsuccessful. However, aortopexy gained good results. Two cases managed conservatively experienced gradual improvement of their symptoms. In adult TBM, plication of pars membranacea was not effective in one case. The insertion of a stent was minimally effective in one case, and distinctly in one polychondritic case. The other four cases managed conservatively have deteriorated gradually. From these findings, a new classification system is proposed.

Adult↗