Biomedical subjects
Publications and source records attributed to H Nagaoka.
After describing determinants for the creation of a successfully used community health care network, our new project of making a mechanism fostering steady development of WAN and LAN among community is presented. Most of the difficulties that inhibit the sound development of community health care system are solved.
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In Shizuoka Prefecture, influenza B viruses belonging to B/Victoria/2/87 lineage caused an outbreak among school children in the off-season of 1998, and the same B viruses were mainly isolated during the following epidemic. Low titer of HI antibody among children for influenza B virus belonging to the same lineage was a recognized factor in the causation of the distinctive epidemic. The herald virus strains seemed to be antigenically similar to the late epidemic virus strains, but the former strains were not genetically close to the latter. This indicates that the herald viruses are not always the parental viruses for the following influenza season.
Kinetic resolution of racemic alcohols, (+/-)-1-(4-substituted phenyl)ethanol and (+/-)-1-(2-naphthyl)ethanol, was done with immobilized green pea, soybean, or buckwheat proteins. The resolution was done stereoselectively by oxidizing only one enantiomer of a racemic alcohol to leave an optically active alcohol with a high purity. In addition, each protein could be reused consecutively at least three times without any decrease of yield or optical purity.
We performed combination chemotherapy adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in 11 patients with gastric cancer and 7 with colorectal cancer. Treatment consisted of a 5-day course of continuous arterial or intravenous infusion of 5-FU (500 mg/body/day), arterial or intravenous infusion of leucovorin (20 mg/body/day) at 6:00 p.m. on days 1-5, arterial or intravenous infusion of mitomycin C (2 mg/body) at 9:00 a. m. on day 5, and arterial or intravenous infusion of cisplatin (20-80 mg/body) at 6:00 p.m. on day 5. The effective rate against gastric cancer was 73%; however, the effective rate against colorectal cancer was 29%. During and after this therapy, there was only a little appetite loss, nausea and stomatitis.
A 19-year old man was admitted to our hospital with fever and productive cough. Chest X-ray films revealed multiple nodular shadows accompanied by a fusing tendency in the right middle field. A diagnosis of bacterial pneumonia was indicated, and the patient was treated with antibiotics. However, because this failed to resolve the nodular shadows, bronchofibroscopy was performed. Examination with a fiberoptic bronchoscope revealed an elevated lesion in the truncus intermedius. Histopathologic examination of a specimen obtained by transbronchial biopsy revealed cryptococcal organisms with the infiltration of monocytes. These findings yielded a diagnosis of pulmonary cryptococcosis with endobronchial lesion. After 6 months of treatment with fluconazole, the multiple nodular shadows disappeared. Comparison of bronchoscopic findings before and after fluconazole treatment clearly demonstrated the efficacy of the therapy.
The purpose of this study was to evaluate the usefulness of continuous retrograde continuous tepid blood cardioplegia (CTBC) in 8 patients underwent multivalve surgery combined with coronary artery bypass grafting (CABG) (Group 1), in comparison with antegrade CTBC in 10 patients with single valve replacement (Group 2). Aortic crossclamp time in Group 1 (187.9 +/- 55.2 minutes) was significantly longer than that (94.1 +/- 27.4) in Group 2 (p < 0.005). There was no hospital death in both groups. Spontaneous recovery rate of the heart beat following aortic declamping was 75% in Group 1, 90% in Group 2 (ns). Postoperative max CK-MB was 87.9 +/- 43.1 IU/l in Group 1, 74.8 +/- 27.0 IU/l in Group 2 (ns). During the early postoperative period, LVSWI significantly increased in both groups, whereas RVSWI showed no significant increase in both groups. Accordingly, in Group 1 in spite of longer aortic crossclamp time comparing Group 2, myocardial protection was considered to be satisfactory. In conclusion, retrograde CTBC is useful as an intraoperative myocardial protection in multivalve surgery combined with CABG which must need much longer aortic cross clamp time.
Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.
A young Japanese woman who appeared to be free from any coronary risk factors was admitted to a local hospital with chest pain. Serological tests showed no evidence of inflammation; however, an electrocardiogram revealed diffuse myocardial ischemia and a coronary angiogram demonstrated isolated bilateral coronary ostial stenoses. Moreover, her serum creatine phosphokinase level was high. On the day following admission, the patient developed severe cardiogenic shock, and she was transferred to our hospital where emergency coronary artery bypass grafting with the saphenous veins was performed using retrograde tepid blood cardioplegia. Recovery of cardiac function was immediate and her postoperative course was uneventful. We suspect that fibromuscular dysplasia was the most likely cause of the ostial stenoses in this patient.
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The metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 was investigated, and their metabolites were compared with separately synthesized materials by measuring 1H-NMR spectra, mass spectra, and HPLC retention times, and evaluated for platelet activating factor (PAF) antagonistic activity. YM461 was metabolized by two different metabolic pathways (cleavage of the thiazolidine ring and oxidation of the benzyl position), whereas YM264 was metabolized by three metabolic pathways. The minor metabolite M7 from YM264 possessed potent PAF antagonistic activity, as strong as YM264 and this existed as an active metabolite. From pharmacokinetics studies, YM264 was almost completely absorbed from the gastrointestinal tract, but readily metabolized in rats. In dogs, pharmacokinetic parameters of YM264 were significantly improved compared to those in rats, and YM264 tended to show better pharmacokinetics than YM461 due to an extension of the half-life period.
(S)-1-(2-Naphthyl)ethanol was yielded by immobilized pea (Pisum sativum L.) protein (IPP) from (R, S) 2-naphthyl ethanol (> 99% ee, yield; about 50%), in which the (R)-enantiomer was selectively oxidized to 2-acetonaphthone. IPP could be reused consecutively at least three times without any decrease of yield and optical purity.
BACKGROUND AND AIM OF THE STUDY: In order to achieve better operative results, myocardial protection for cardiac valve re-replacement must be further improved. The aim of this study was to compare the efficacy of continuous warm blood cardioplegia (CWBC) with that of intermittent cold potassium cardioplegia (ICPC) in cardiac valve re-replacement. METHODS: A total of 49 consecutive patients underwent elective cardiac valve re-replacement via sternal re-entry; 27 patients received CWBC and 22 ICPC. During surgery, a narrower dissection of the heart was used in the CWBC group. The myocardial protective effects and operative outcome were analyzed in the two groups. RESULTS: Two ICPC patients died in hospital, one from cerebral bleeding and one from low output syndrome. The rate of spontaneous recovery of the heart-beat after aortic declamping was significantly higher in CWBC patients than in the ICPC group (92.3% versus 13.6%, p < 0.001). Postoperatively, maximum serum creatine kinase-MB levels were significantly lower in CWBC patients than in ICPC patients (25.5 +/- 6.0 versus 81.1 +/- 26.0 IU/l, p < 0.02). Left ventricular stroke work index in the CWBC group showed significantly better recovery in the early postoperative period compared with that in the ICPC group. Extraction of myocardial oxygen (range: 0.33 to 0.35) and lactate (range: -0.02 to 0.14) in CWBC patients was maintained within the normal range immediately after aortic declamping and in the early postoperative period. In contrast, in ICPC patients extraction of myocardial oxygen (range: 0.18 to 0.23) and lactate (range: -0.27 to -0.17) was impaired during the same period. Postoperative (24-h) blood loss was significantly less in CWBC patients than in ICPC patients (p < 0.02). CONCLUSION: In cardiac valve re-replacement surgery through sternal re-entry, and without wide exposure of the heart, continuous warm blood cardioplegia provides much greater myocardial protection than does intermittent cold potassium cardioplegia.
Emergency coronary artery bypass grafting (CABG) for acute coronary syndrome due to left main coronary artery (LMCA) disease still remains to be a therapeutic challenge. Seventy consecutive patients underwent CABG for LMCA disease were divided into two groups, that is 21 patients with emergency CABG (Group E) and 49 with scheduled CABG (Group S). There were four in-hospital deaths (mortality rate: 19.1%) in Group E and two (4.1%) in Group S. Three of 4 deaths in Group E had cardiogenic shock associated with acute myocardial infarction (AMI) preoperatively, and low output syndrome followed by multiple organ failure postoperatively. All of four deaths cases received intermittent cold GIK cardioplegia as an intraoperative myocardial protection. On the other hand, seven cases, received retrograde continuous warm blood cardioplegia (CWBC), including AMI with shock due to LMCA occlusion and concomitant CABG and valve replacement complicated with aortic regurgitation, all survived operations. In conclusion, retrograde CWBC may be useful as an intraoperative myocardial protection in emergency CABG for AMI with shock due to LMCA occlusion.
Combination chemotherapy with multiple drugs (FLMP therapy), in which the drugs were determined based on biochemical modulation and the dosing schedule was established in accordance with the circadian rhythms of the human body, was performed in cases of advanced recurrent gastric cancer. The drugs were administered according to the following schedule: 500 mg of 5-FU (continuous) on days 1-5 (the dose was increased during the night), 20 mg of LV on days 1-5 (at 6 PM), 2 mg of MMC on day 5 (at 9 AM) and 60-80 mg of CDDP on day 5 (at 6 PM). A five-day course was administered by intravenous drip or hepatic arterial infusion at intervals of 4 weeks. Of 14 patients treated, the effect was estimated to be CR in 3, PR in 6, NC in 3, and PD in 2. The effectiveness rate was 62.3% overall, and the rate by administration route was 6/10 (60.0%) for i.v. and 3/4 (75.0%) for i.a. The side effects were slight. Those of grade 3 or more included anorexia in 5%, nausea and vomiting in 1%, stomatitis in 1% and leukopenia in 1%. This therapy, administered in accordance with the theory of chronotherapy, caused few side effects, and thus is considered a promising treatment for gastric cancer.
CD40 activates nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) subfamily, including extracellular signal-regulated kinase (ERK). The CD40 cytoplasmic tail interacts with tumor necrosis factor receptor-associated factor (TRAF)2, TRAF3, TRAF5, and TRAF6. These TRAF proteins, with the exception of TRAF3, are required for NF kappa B activation. Here we report that transient expression of TRAF6 stimulated both ERK and NF kappa B activity in the 293 cell line. Coexpression of the dominant-negative H-Ras did not affect TRAF6-mediated ERK activity, suggesting that TRAF6 may activate ERK along a Ras-independent pathway. The deletion mutant of TRAF6 lacking the NH2-terminal domain acted as a dominant-negative mutant to suppress ERK activation by full-length CD40 and suppress prominently ERK activation by a deletion mutant of CD40 only containing the binding site for TRAF6 in the cytoplasmic tail (CD40 delta 246). Transient expression of the dominant-negative H-Ras significantly suppressed ERK activation by full-length CD40, but marginally suppressed ERK activation by CD40 delta 246, compatible with the possibility that TRAF6 is a major transducer of ERK activation by CD40 delta 246, whose activity is mediated by a Ras-independent pathway. These results suggest that CD40 activates ERK by both a Ras-dependent pathway and a Ras-independent pathway in which TRAF6 could be involved.
Norwalk-like virus genes were detected by RT-PCR in the caecum contents of pigs. Positive PCR products were produced from four out of 1,117 samples by nested PCR using human SRSV primers. Nucleotide sequences between 4,561 and 4,852 numbered according to the Norwalk virus genomic RNA in the RNA polymerase region were determined. Between the Norwalk virus sequence and the sequences detected in pigs, there was 58.2% to 59.9% sequence homology. The swine sequences were located on genogroup II of human SRSVs, but formed a subgroup in the phylogenetic tree of caliciviruses.