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Biomedical subjects

Nobuyuki Kobayashi

Publications and source records attributed to Nobuyuki Kobayashi.

At least 19 recordsLinked to original sources
PubMed2006

Amiodarone pulmonary toxicity: a patient with three recurrences of pulmonary toxicity and consideration of the probable risk for relapse.

A 44-year-old man was treated with amiodarone for dilated cardiomyopathy. After 53 months, he developed amiodarone-induced interstitial pneumonia. Amiodarone treatment was terminated, and the patient was given corticosteroids. These treatments were effective. However, pneumonitis recurred whenever prednisolone was reduced to less than 5 mg per day. Considering the patient's background characteristics, we considered his body mass index (BMI, kg/m(2)) and found his to be high. When four additional patients with amiodarone pulmonary toxicity were reviewed at our institute, a correlation between BMI and the duration of shadow disappearance was found (R(2)=0.8695). Because amiodarone is lipophilic, the patient's high BMI might have influenced the repeated appearance of pulmonary toxicity.

Adult↗
PubMed2006

Identification of Hsc70 as an influenza virus matrix protein (M1) binding factor involved in the virus life cycle.

Influenza virus matrix protein 1 (M1) has been shown to play a crucial role in the virus replication, assembly and budding. We identified heat shock cognate protein 70 (Hsc70) as a M1 binding protein by immunoprecipitation and MALDI-TOF MS. The C terminal domain of M1 interacts with Hsc70. We found that Hsc70 does not correlate with the transport of M1 to the nucleus, however, it does inhibit the nuclear export of M1 and NP, thus resulting in the inhibition of viral production. This is the first demonstration that Hsc70 is directly associated with M1 and therefore is required for viral production.

Active Transport, Cell Nucleus↗
PubMed2006

Leflunomide-induced pneumonitis in a patient with rheumatoid arthritis.

Leflunomide is a disease-modifying antirheumatic drug (DMARD) that has been available in Japan since August 2003. Leflunomide-induced interstitial pneumonitis has not been reported as an adverse effect in other countries. We report a suspected case of leflunomide-induced interstitial pneumonitis. A 77-year-old woman with rheumatoid arthritis and a history of methotrexate-induced pneumonitis developed sudden-onset dyspnea on exertion about 2 months after the administration of leflunomide. She maintained a high concentration of an active metabolite of leflunomide for more than 3 weeks after withdrawal of the drug. She did not respond to treatment and died. Leflunomide must be administered with caution to patients with a history of interstitial pneumonitis or drug-induced pneumonitis. If leflunomide-induced pneumonitis is suspected, the plasma concentration must be immediately checked, along with elimination and withdrawal of the medication.

Adjuvants, Immunologic↗
PubMed2006

Establishment of a new cell line inducibly expressing HIV-1 protease for performing safe and highly sensitive screening of HIV protease inhibitors.

The human immunodeficiency virus type 1 (HIV-1) protease (PR) plays an essential role in processing viral polyproteins into mature proteins. As a result, it is a major target for the development of drugs against AIDS. However, due to the rapid emergence of drug-resistant HIV, the development of novel HIV PR inhibitors is urgently needed. We recently established a new cell line E-PR293 which can be used as a safe, convenient and highly efficient assay system to screen HIV-1 PR inhibitors. In the cells, the HIV-1 PR is expressed in a chimeric protein with the green fluorescence protein (GFP). This assay measures the PR activity as a function of either the fluorescence of GFP or the cytotoxic activity of HIV-1 PR which is expressed in the cell. E-PR293 cells were maintained in the presence of doxycycline, which suppresses the expression of HIV-1 PR. The removal of doxycycline induces the expression of HIV-1 PR, which is used to screen HIV-1 PR inhibitors. In E-PR293 cells, the 50% inhibitory concentration of the cytotoxic effects by nelfinavir and saquinavir were as low as nanomolar levels, almost equal to those found in the HIV-infection assay.

Cell Line↗
PubMed2006

Tuberous sclerosis complex complicated by pulmonary multinodular shadows.

A 41-year-old woman with a history of epilepsy was referred for multiple nodular ground-glass opacities on a chest computed tomography (CT) scan. They were initially suspected of representing atypical adenomatous hyperplasia or well-differentiated adenocarcinoma. However, the subsequent brain CT and magnetic resonance imaging (MRI) scans revealed a coarse nodular calcification and cortical tubers. A subungual fibroma was also noted. Histological examination of a video-assisted thoracoscopic lung biopsy specimen disclosed multiple nodules of type II pneumocyte hyperplasia with septal thickening. Based on all of these findings taken together, a diagnosis of tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia (MMPH) was made.

Adult↗
PubMed2006

Pneumoconiosis associated with an esophageal ulcer and uptake revealed in FDGPET.

A 76-year-old man with a past history of pneumoconiosis visited the Department of Gastroenterology in our hospital suffering from dysphagia. Gastroscopy revealed an esophageal ulcer on the top of a torus lesion. Chest computed tomography (CT) revealed it was caused by a swollen lymph node in the mediastinum. Squamous cell carcinoma related antigen (SCC) was elevated to 1.8 ng/ml. To rule out malignancy, we performed fluorine-18 deoxyglucose positron emission tomography (FDGPET) which revealed a significantly increased uptake in a nodular lesion in the right upper lobe and mediastinal lymph nodes. Biopsy and cytology of the nodular lesion revealed only pneumoconiosis. We must be careful when we interpret the findings of FDGPET in pneumoconiosis patients.

Aged↗
PubMed2006

Association of functional influenza viral proteins and RNAs with nuclear chromatin and sub-chromatin structure.

Transcription and replication of the influenza virus genome occur in the nucleus. However, the intra-nuclear localization of viral RNP complexes and the function of nuclear domains involved in viral transcription and replication, if any, are not well known. In the present study, we determined the intra-nuclear localization of viral proteins and viral RNAs and the in vitro RNA synthesis activity of viral RNP complexes associated with distinct nuclear fractions prepared from infected nuclei. A majority of viral RNA polymerases and M1 were recovered in DNase-sensitive fractions, whereas some portion of RNA polymerases and approximately 25% of NP were tightly associated with so-called nuclear matrix fractions. The amount of vRNA associated with the nuclear matrix was significantly more than that of cRNA. The in vitro viral RNA synthesis activity was detected in DNase-insensitive fractions, including the nuclear matrix. In contrast, newly synthesized viral RNAs were recovered in the DNase-sensitive fraction. These observations suggest that vRNP complexes are, at least partially, associated with densely packed chromatin, where viral transcription and replication occur, and the newly synthesized vRNP complexes to be transported into the cytoplasm are released into the nucleoplasm.

Animals↗
PubMed2006

Laparoscopic Heller myotomy with Toupet fundoplication for achalasia straightens the esophagus and relieves dysphagia.

BACKGROUND: A standard procedure for the treatment of achalasia remains to be established. We assessed the usefulness of a laparoscopic Heller myotomy with a Toupet fundoplication (LHT). METHODS: LHT was performed in 30 patients (12 men, 18 women; mean age, 41.8 y) who had esophageal achalasia with severe dysphagia. Caution was exercised when the esophagus was pulled downward and straightened. Symptoms and esophageal function were evaluated before and after surgery. RESULTS: The esophagus was straightened surgically in 22 (88%) of 25 patients with esophageal curvature on preoperative esophagography. The dysphagia score decreased to 1.7 +/- 1.2 (mean +/- SD) points from a preoperative value of 10. The lower esophageal sphincter pressure decreased significantly. Two patients (7%) had esophageal diverticula as postoperative sequelae. Pathologic acid reflex was noted in 3 patients (12%). CONCLUSIONS: LHT is a useful procedure for straightening the esophagus, reducing lower esophageal sphincter pressure, and relieving dysphagia in patients with achalasia.

Adult↗
PubMed2006

Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: relevance of cellularity and p27kip1.

The aim of the present study was to determine whether expression of molecules associated with cell cycle regulation and apoptosis might reflect tumor grade and patients' prognosis of gastrointestinal stromal tumor (GIST). Forty-nine cases of gastric GIST were divided into three grades; low, intermediate, and high risk. Ki-67, cyclin A, cyclin D1, cyclin E, p16(Ink4), p21(Waf1), p27(Kip1), cyclin-dependent kinase (cdk)2, cdk4 and single-strand DNA (ssDNA) were immunohistochemically stained and assessed. Ki-67, ssDNA, cyclin A and cdk2 had higher labeling indices (LI) in high-risk than in low-risk cases. Cyclin E expression was greater in the intermediate- than in the low-risk grade. On Kaplan-Meier analysis, tumor size, necrosis, cellularity, Ki-67, ssDNA, and cyclin A LI were significantly correlated with disease-free survival. Necrosis, cellularity, and Ki-67 LI were significant as prognostic factors on univariate, and Ki-67 LI on multivariate Cox hazard tests. Within the high-risk grade, high cellularity and low p27(Kip1) subgroups had the worst prognosis. The histological grade is related to cell turnover, assessed in terms of Ki-67, ssDNA, cyclin A, cyclin E, and cdk2 levels. Ki-67, ssDNA, and cyclin A are useful for prediction of prognosis, with cellularity and p27(Kip1) expression as further prognostic factors in high-risk cases.

Aged↗
PubMed2006

[A case of pulmonary tuberculosis complicated with an orthotopic liver transplantation].

The infectious disease is one of the most important complications related to the organ transplantation. Patients using immunosuppressive agents often present atypical tuberculosis and the treatment of such case is far more difficult in some cases due to the liver damage and/or the drug interaction. We report a case of pulmonary tuberculosis in a patient of 60-year-old man using tacrolimus after an orthotopic liver transplantation. He had liver transplanted orthotopically for the long-term history of chronic hepatitis B and subsequent liver failure on January 28, 2004. An abnormal shadow was first detected on his chest X-ray film on October, 2004. He was admitted to our hospital after the smear of the gastric juice showed some acid-fast bacilli and tubercle bacilli were confirmed by polymerase chain reaction (PCR). Tuberculin skin test was positive (erythema 10 x 10) and the computed tomography (CT) scan of his chest revealed a nodular opacity with some smaller nodules scattered around in the right upper lobe. We started four anti-tuberculous drugs other than pyrazinamide (PZA) and rifampicin (RFP), which included isoniazid (INH), ethambutol (EB), streptomycin (SM), levofloxacin (LVFX). The liver enzyme was transiently elevated (AST 123 IU/I, ALT 103 IU/I) but improved after desensitization against INH. The blood concentration of tacrolimus preserved between 5 and 7 ng/ml and there was no need to change the dosage.

Humans↗
PubMed2006

[Development of new surgical tools, Q-PAL and HP-Jet for endoscopy only used unilateral transnasal approach for pituitary adenomas].

UNLABELLED: The aim of this study is to present surgical techniques and results of endoscope-assisted transnasal approach (TNA) for pituitary adenomas. It is a new alternative for Hardy's surgery (TSS). We performed TNA assisted by only endoscope through single nostril. METHOD: We enter the sphenoid sinus directly through the natural ostium and ablate neither the nasal septum nor the vomer bone. We found the hardest problem of this method resides in its deep and narrow working space which obstructs usage of two tools at same time. To overcome this problem we developed two surgical tools, Q-PAL and HP-Jet. Q-PAL is combination of PAL and suction. We place flexible PAL wire electrode through suction tube so as PAL tip protrudes from suction tip. This eliminates coagulation smoke which otherwise disturbs surgeons view. HP-Jet is a combination of a suction tool and an irrigator. The irrigator is connected to syringe containing saline. Saline is injected manually from tip bursting up tumor tissue with its jet pressure. It is safe and effective instrument suitable for extirpation of rather fragile tissue like adenomas existing in deep and blind spaces. CASES: Since 2004 we have operated on 16 patients using endoscopic TNA. Eight were non-functioning adenomas, and 8 functioning. RESULTS: Results of surgery were compared with those of 10 cases operated by TSS. More than 70% removal of adenoma was achieved in 75% of cases with TNA, but in only 71% with TSS. Postoperative CSF rhinorrhea was seen in one case. Four cases showed postsurgical transient diabetes insipidus. We had no case with postsurgical infection. With the help of instruments having multiple functions in single probe such as Q-PAL and HP-Jet, we can execute endoscopic TNA more smoothly and more safely.

Adenoma↗
PubMed2006

[A case of pineal pure germinoma metastasized to the lumbosacral extradural space 8 years after initial therapy. Case report and review of literature].

An 11-year-old boy first presented with a pineal tumor identified by neuroimaging but without positive serum or cerebrospinal fluid markers. The tumor disappeared after the craniotomy and following cranial irradiation. The pathologic diagnosis of the tumor was of a pure germinoma. Eight years later he returned to the hospital with spinal epidural metastasis from the pineal germinoma and required surgery. Intraoperative findings showed that the spinal tumor was solitarily located in the epidural space. Pathologically the tumor was a pure germinoma metastasis. He was treated by a combination of whole spinal irradiation and chemotherapy. The tumor disappeared after the therapy. A pineal germinoma occasionally disseminates through the ventricular system and spinal subarachnoid region. However, a solitary spinal epidural metastasis from pineal germinoma has rarely been reported. Regarding the route of this metastasis, we speculate that the CSF dissemination of the germinoma cells occurred first and some of those cells were trapped in the spinal nerve sleeve and extended into the epidural space.

Adult↗
PubMed2006

[Only used unilateral transnasal approach applied endoscopic sinus surgery for pituitary adenomas].

Endoscope-assisted transnasal approach (TNA) for pituitary adenoma is a new alternative for Hardy's surgery (TSS). We performed TNA using only an endoscope through unilateral nostril. In our approach to sphenoid sinus, we apply method of endoscopic sinus surgery (ESS-TNA). We enter the sphenoid sinus directly through the natural ostium and do not brake the nasal septum nor vomer bone. Since September 2004 we had operated on 12 patients by endoscopic TNA. Six were non-functioning adenomas, and 6 were functioning adenomas. We are first to open the ethomoid sinus to make the space for middle concha to be displaced laterally. Secondary, we widen the natural ostium of the sphenoid sinus, retracting the middle concha laterally. The results were compared with those in 10 cases by TSS operated in our institute. Adenoma removal more than 80% was achieved in 58% by endoscopic TNA whereas in 50% by TSS. We had no case with postsurgical infection. Transient DI occurred in 4 cases and 1 case showed permanent. CSF rhinorrhea was seen in the case having small empty sellae in front of adenoma. For this case, we packed the fat tissue at the floor of the sella with endoscope under local anesthesia to close the fistula. Three cases that had hemianopsia before surgery showed the recovery postoperatively. In 6 functional adenoma, postoperative endocrinological examinations showed normalization in 3 cases and improvements in 3 cases. Postsurgical hospitalization days were 11.4 by endoscopic TNA whereas 15.4 by TSS. Our method showed same or better results than TSS in the removal rate and complication rate whereas the postoperative duration of nasal packing and hospitalization days were shorter than TSS.

Adenoma↗
PubMed2006

[Case of cavitary coccidioidomycosis with fungus balls in the apices of both lungs].

Pulmonary cavitary coccidioidomycosis with a fungus ball was observed in a immunocompetent case. A 32-year-old Japanese man visited Arizona to play golf. After 1 month he consulted a local hospital complaining of a prolonged cough and hematopysis. The laboratory examination revealed eosinophillia and chest radiograph showed 2 cavitary lesions, surrounded by small nodules in the apices of both lungs. Pulmonary tuberculosis was suspected and treated with 4 antituberculosis drugs for 3 months. However, the cavities enlarged and he was admitted to our hospital for further examination and treatment. Transbronchial lung biopsy was performed and serologically, bacteriologically and histologically a diagnosis of chronic coccidioidmycosis was made. It is very rare for fungus ball formation and coexistence of spherules and hyphae of Coccidioides immitis to be seen. Fluconazole was temporarily effective, causing cavities to shrink and eosinophilia to decrease, however Amphotericin B needed to be used later. Eosinophilia was closely related to the severity of the disease gravity.

Adult↗
PubMed2006

[A case of long-term survival of 3-years 4 months after combination chemotherapy of MTX, 5-FU and low-dose CDDP (MFP) for type 4 gastric cancer with pleuritis, peritoneal dissemination and Krukenberg tumor].

A 41-year-old woman presented to the Department of Obstetrics and Gynecology of our hospital because of abdominal distension and irregular genital bleeding. Computed tomography and ultrasonography of the abdomen revealed bilateral ovarian tumors, massive ascites, and bilateral pleural effusion. Type IV advanced gastric cancer was diagnosed on upper gastrointestinal endoscopy. The patient was admitted to our department. She received 3 courses of combination chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin. Pleural effusion and ascites disappeared. Surgery (total gastrectomy, resection of the tail of the pancreas, lymph-node dissection, total hysterectomy, and adnexectomy) was performed, and the patient was discharged. Chemotherapy was repeated after surgery. Lymph-node metastasis recurred 1 year 8 months after the start of chemotherapy. Treatment was switched to irinotecan plus cisplatin, and the lymph nodes shrank. After 9 months, 3 courses of TS-1 were administered. Two years 10 months after starting chemotherapy, abdominal and low back pain developed. Bone scintigraphy revealed bone metastasis. Lymph node swelling was present. The patient responded to radiotherapy with chemotherapy (cisplatin plus 5-fluorouracil). Subsequently, abdominal computed tomography showed lymph-node swelling, multiple metastases to the liver, ascites, and a right pleural effusion. She was readmitted to the hospital and received intraperitoneal chemotherapy with cisplatin. Her condition deteriorated, and she died. The patient survived for about 3 years 4 months after the start of treatment. Chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin may thus be an effective therapeutic option in patients who have advanced gastric cancer with peritoneal dissemination.

Adult↗
PubMed2006

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Aged↗
PubMed2005

Adenoviral vector-mediated gene transfer of IL-13Ralpha2 chain followed by IL-13 cytotoxin treatment offers potent targeted therapy for cytotoxin-resistant cancers.

Previous studies demonstrated that IL-13Ralpha2 chain-overexpressing cancer cells were highly sensitive to IL-13 cytotoxin (IL13-PE38QQR) and could be targeted by cytotoxin treatment. However, the majority of human tumors do not express high levels of IL-13Ralpha2 chain. To expand the IL-13 cytotoxin-mediated cancer targeting therapy, we combined cytotoxin treatment with gene transfer of IL-13Ralpha2 chain. We constructed a recombinant adenoviral vector carrying the human IL-13Ralpha2 gene (Ad-IL-13Ralpha2), which expresses high levels of IL-13Ralpha2 chain on infected cells. Human cancer cell lines A549 and HOS, which originally show no IL-13Ralpha2 expression and little sensitivity to IL-13 cytotoxin, were effectively converted to become sensitive to this cytotoxin after Ad-IL-13Ralpha2 infection. The CC(50) of IL-13 cytotoxin for Ad-IL-13Ralpha2-infected A549 cells was <10 ng/ml, whereas the CC(50) for uninfected or control vector-infected cells was >500 ng/ml. We also examined the antitumor activity of IL-13 cytotoxin in an established xenograft model of cytotoxin-resistant human lung tumor. Only a single i.t. injection of Ad-IL-13Ralpha2 markedly enhanced the sensitivity of established tumors to IL-13 cytotoxin treatment; furthermore, this antitumor effect was significantly sustained for more than 1 month after the last treatment with IL-13 cytotoxin. Taken together, these results suggest the combination of adenoviral vector-mediated IL-13Ralpha2 gene transfer and IL-13 cytotoxin administration can be an effective targeting approach for several types of IL-13 cytotoxin-resistant cancers which show no or little expression of IL-13Ralpha2 chain.

Adenoviridae↗