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Biomedical subjects

K Yazawa

Publications and source records attributed to K Yazawa.

At least 37 records · Page 2Linked to original sources

Bifidobacterium longum as a delivery system for cancer gene therapy: selective localization and growth in hypoxic tumors.

A fundamental obstacle in gene therapy for cancer is the specific delivery of an anticancer gene product to a solid tumor, and yet no systemic delivery system that specifically targets solid tumors currently exists. A strain of domestic bacteria, Bifidobacterium longum, which is nonpathogenic and anaerobic, selectively localized and proliferated in several types of mouse solid tumors after systemic application. In this report, we further describe a novel approach to cancer gene therapy in which genetically engineered Bifidobacterium is used as a tumor-specific vector. Similarly to wild-type B. longum, genetically engineered B. longum could be detected in tumor tissue only and was not found in a large survey of normal mouse tissues after intravenous injection. This finding strongly suggests that obligate anaerobic bacteria such as Bifidobacterium can be used as highly specific gene delivery vectors for cancer gene therapy.

Animals↗

Changes in cardiopulmonary parameters during upper gastrointestinal endoscopy in patients with heart disease: towards safer endoscopy.

BACKGROUND AND STUDY AIMS: Gastrointestinal endoscopy is an invasive examination. The aims of this study were to elucidate the effects and risks of upper gastrointestinal endoscopy with regard to cardiopulmonary functions in patients with heart disease, and to establish safety guidelines for use during endoscopy in this particular group of patients. PATIENTS AND METHODS: The patients involved were 53 inpatients in whom upper gastrointestinal endoscopy was carried out before cardiac surgery. Their cardiac functions had been evaluated previously. Electrocardiography with two leads (II, V5) was used, and blood pressure and peripheral oxygen saturation (SpO2) were monitored throughout the procedure. The relationship between the changes in cardiopulmonary parameters during endoscopy and the cardiac functions was analyzed. RESULTS: Heart rate increased immediately after insertion of the endoscope (P < 0.01). There was a significantly higher incidence of ventricular and supraventricular extrasystoles during observation of the second portion of the duodenum (P < 0.05). A lower cardiac index (P < 0.05) and a higher New York Heart Association (NYHA) functional classification (P < 0.05) were found in patients with oxygen desaturation than in patients without it. Two patients with severe coronary artery lesions showed marked ST-T depression, and these ischemic changes were thought to be due to increase in cardiac work during endoscopy. CONCLUSIONS: Upper gastrointestinal endoscopy has many adverse effects on cardiopulmonary functions in patients with heart disease. In our study, the clinical value of very close monitoring and administration of oxygen for patients with heart disease was confirmed by objective data.

Aged↗

Dietary effects of eicosapentaenoic and docosahexaenoic acid esters on lipid metabolism and immune parameters in Sprague-Dawley rats.

Sprague-Dawley rats were fed eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) ethyl esters at the 2% level for 3 weeks to clarify their effects on immune functions. In the rats fed EPA or DHA, serum cholesterol, triglyceride, and phospholipid (PL) levels were significantly lower than those in the rats fed safflower oil. In PL fractions of serum, liver, lung, splenocytes, and peritoneal exudate cells (PEC), increases in linoleic and dihomo-gamma-linolenic acid contents and a decrease in arachidonic acid (AA) content were observed in the rats fed EPA or DHA. In addition, the EPA content increased in the rats fed EPA and DHA. In the rats fed EPA or DHA, a decrease of LTB4 productivity and an increase of LTBs productivity were observed in the PEC, in response to the treatment with 5 microM calcium ionophore A23187 for 20 min. The changes in leukotriene production were more marked in EPA-fed rats than in DHA-fed rats. These results suggest that dietary EPA affects lipid metabolism and leukotriene synthesis more strongly than DHA.

Animals↗

Structures of ADP-ribosylated rifampicin and its metabolite: intermediates of rifampicin-ribosylation by Mycobacterium smegmatis DSM43756.

23-(O-ADP-Ribosyl)rifampicin [RIP-TAs (3, Na+ form), RIP-TAf (4, H+ form)] was obtained as an intermediate in the conversion process of rifampicin (1) to RIP-Mb (2) that is mediated by cell homogenates of Mycobacterium smegmatis DSM43756 or of Escherichia coli carrying a mycobacterial mono(ADP-ribosyl) transferase gene, in the presence of NADH. 23-[O-(5'-Phosphoribosyl)]rifampicin (5, RIP-TAp) was also obtained by the reaction of rifampicin with NADH in the presence of a homogenate of M. smegmatis. The structures of 3, 4, and 5 were determined by means of MS and NMR analyses.

ADP Ribose Transferases↗

Administration of docosahexaenoic acid influences behavior and plasma catecholamine levels at times of psychological stress.

The purpose of the present research was to clarify the effect of docosahexaenoic acid (DHA) intake on behavior and plasma catecholamines (CA). In Study 1, 42 students took either DHA-rich oil capsules containing 1.5-1.8 g DHA/d or control oil capsules containing 97% soybean oil plus 3% of another fish oil for 3 mon in a double-blind fashion. They took a psychological test (PF Study) at the start and end of the study. This study started at the end of summer vacation and ended just before the final exams. In the control group, external aggression (aggression against others) in PF Study was significantly increased at the end of the study as compared with that measured at the start (+8.9%), whereas it was not significantly changed in the DHA group (-1.0%). In a similar double-blind study (Study 2), we measured external aggression under nonstressful conditions. External aggression slightly decreased in the control group, whereas there were no significant changes in the DHA group. In Study 3 with 14 students, plasma CA were measured at the start and end of capsule administration period of 2 mon. Subjects were under continuous stress of the final exams that lasted throughout the whole study period. The ratio of plasma epinephrine to norepinephrine concentrations was significantly increased in the DHA group (78%), whereas it stayed at the same level in the control group. In Study 4, mice were fed either DHA-deficient diet or -sufficient diet for 4 wk, and their rearing frequency (an anxiety index) was measured. In the DHA-sufficient group, the rearing frequency was significantly less than in the other group. These effects of DHA intake may be applied to people in an attempt to ameliorate stress-related diseases.

Adult↗

Reresection for local recurrence of rectal cancer.

Local recurrence is one of the major reasons that rectal cancer surgery is unsuccessful. The aim of this study was to investigate the surgical characteristics of patients undergoing reresection for local recurrence of rectal cancer. A total of nine patients were enrolled in this study, six of whom underwent total pelvic exenteration, one, posterior exenteration, one, abdominoperineal resection with sacral resection, and one, lymph node dissection alone. The mean operative time was 8 h 15 min, and the mean operative blood loss was 2 325 ml. Although major postoperative complications occurred in four patients (44%), there were no postoperative or hospital deaths. Lateral lymph node metastasis was detected in all four patients whose lateral lymph nodes were dissected or extirpated at the reresection. Two patients survived for more than 5 years without rerecurrence, and the cumulative 5-year survival rate was 26%. The para-aortic lymph nodes were the most common site of first rerecurrence. The results of this study indicate that patients who undergo reresection for local recurrence of rectal cancer are at high risk of devel-oping lateral or para-aortic nodal metastasis. Nevertheless, reresection may be a therapeutic option for the local recurrence of rectal cancer.

Adenocarcinoma↗

Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells.

We investigated the relative effects of n-3 eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) on the plasma membrane fluidity of endothelial cells (EC) cultured from the thoracic aorta by determining fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and its cationic derivative trimethylamino-DPH (TMA-DPH). Fluidity assessed by TMA-DPH demonstrated no significant differences in plasma membranes of vehicle (dimethyl sulfoxide; DMSO)-, EPA-, and DHA-treated EC. Plasma membrane fluidity assessed by DPH polarization, however, was significantly higher in the order of DHA > EPA > DMSO. Total cholesterol content decreased significantly by 28.4 and 15.9% in the plasma membranes of DHA- and EPA-treated cells, respectively. Total phospholipid content remained unaltered in the plasma membranes of the three groups of cells; however, the molar ratio of total cholesterol to phospholipid decreased significantly only in the membranes of DHA-treated EC. The unsaturation index in the plasma membranes of EPA- and DHA-treated cells increased by 35.7 and 64.3%, respectively, compared with that in the plasma membranes of control cells. The activities of catalase and glutathione peroxidase in the whole-cell homogenates, and levels of lipid peroxides in either the whole-cell homogenates or in plasma membrane fractions were not altered in EPA- or DHA-treated EC. These results indicate that the influence of DHA is greater than that of EPA in increasing plasma membrane fluidity of vascular EC. We speculate that the greater effect of DHA compared to EPA is due to its greater ability to decrease membrane cholesterol content or the cholesterol/phospholipid molar ratio, or both, and also to its greater ability in elevating the unsaturation index in the plasma membranes of EC.

Animals↗

Identification and characterization of a new intermediate in the ribosylative inactivation pathway of rifampin by Mycobacterium smegmatis.

Mycobacterium smegmatis DSM 43756 inactivates rifampin by ribosylation. To study this process of rifampicin, all possible inactivated forms of the antibiotic were extracted and purified. Structural studies showed the presence of a new inactivation product, designated RIP-TAp(23-phosphoribosyl-rifampin). Formation of 23-(O-ADP-ribosyl)rifampin (RIP-TAs) is the first step, followed by removal of AMP to give rise to the newly identified compound. Lastly, dephosphorylation leads to formation of 23-ribosyl-rifampin (RIP-Mb). Feeding experiments with the ADP-ribosylated antibiotic obtained from the cell homogenates of an Escherichia coli strain carrying the cloned M. smegmatis gene confirmed this rifampin inactivation process.

Antibiotics, Antitubercular↗

Hepatic resection of giant cavernous hemangioma of the liver.

Surgical treatment of giant hemangioma of the liver is still controversial. The aim of this study is to examine the efficacy of hepatic resection for giant hemangioma of the liver. Twenty patients with giant cavernous hemangioma of the liver were treated by hepatic resection. The mean diameter of the hemangiomas was 13.9 cm (range, 6.5-30 cm). The surgical outcome was reviewed retrospectively. Major hepatectomy was performed in 14 patients and minor hepatectomy in 6 patients. Complications occurred in 7 of the 20 patients treated by hepatic resection. At a mean follow-up of 79 months (range, 12-173 months), 18 patients were symptom free whereas 2 patients had died--one died of pneumonia at 2 years and the other died of gastric cancer 6 years after surgery. Mean intraoperative hemorrhage and blood transfusion in all patients was 4,343 mL (range, 270-24,000 mL) and 1,860 mL (range, 0-8,800 mL) respectively. In the seven patients with preoperative high levels of fibrin degradation products (FDP), mean intraoperative hemorrhage and blood transfusion were markedly higher (9,371 mL and 3,714 mL respectively) than in the 13 patients without abnormal FDP (1,603 mL and 900 mL respectively). Preoperative hematologic status returned to normal after operation in all patients. Hepatic resection is a useful treatment for giant cavernous hemangioma of the liver. More careful management to reduce intraoperative hemorrhage is recommended to increase the safety of surgery, particularly in patients with preoperative abnormal FDP.

Adult↗