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Biomedical subjects

I Yamamoto

Publications and source records attributed to I Yamamoto.

At least 73 records · Page 4Linked to original sources

In vivo gene gun-mediated DNA delivery into rodent brain tissue.

Various types of gene transfer into live tissues have been tried. However, in vivo gene transfer into brain tissue or neuronal cells without virus vector has required a great effort. Particle-mediated gene transfer into live brain tissue was thought to be impossible because of its fragility and the mechanical problem of a previous type of gene gun. In addition, particle-mediated DNA transfer into monolayer-cultured cells without mechanical damage has been difficult. We successfully transferred DNA into rodent live brain tissue and also into monolayer-cultured cells without mechanical damage by using a new type of gene gun and also confirmed gene expression in the brain. This new method represents another variation of gene transfer into the brain.

Animals↗

[Laparoscopic radical nephrectomy for renal cell carcinomas; report on two initial cases].

We recently performed a laparoscopic radical nephrectomy (LRN) on two patients with a renal cell carcinoma. Case 1, a 72-year-old man, was diagnosed as having a renal cell carcinoma 2.5 cm in diameter in the right kidney, and also a submucosal tumor of the cecum. LRN and laparoscopically assisted ileocecal resection were performed using a transperitoneal approach on September 28, 1999. Total operation time and blood loss during the operation were 308 minutes and 320 ml, respectively. The operation time needed for LRN, which was calculated as the total operation time minus the time spent on ileocecal resection, was 199 minutes. There were no complications after surgery, and the patient was recommended for discharge on the 7th postoperative day, but was actually discharged on the 10th postoperative day. Case 2, an 81-year-old man, was diagnosed as having a renal cell carcinoma 3.0 cm in diameter in the right kidney. He had been undergone a total gastrectomy for a gastric carcinoma at age 77, and a sigmoidectomy for a sigmoid colon carcinoma at age 79. A transperitoneal approach was applied for LRN to detect any recurrence of previous carcinomas on September 30, 1999. During adhesiolytic procedures, the colon was injured due to an inappropriate maneuver of the grasping forceps. A small laparotomy (5 cm) was required for repair of the colon. The total operation time and blood loss during surgery were 370 minutes and 850 ml. The operation time calculated from the video of LRN was 274 minutes. Two additional surgical procedures were required in this case. The first was for a postoperative intraperitoneal hemorrhage due to the hemoclip dropping out of the small vein. The second was for hemorrhage in the abdominal wall. Fortunately, the clinical course after surgery was good and the patient was discharged on the 8th postoperative day. There were no complications in case 1. Omitting ileocecal resection was considered to speed up oral intake, leading to earlier discharge. However, major complications occurred in case 2. It is important to clarify the cause of postoperative hemorrhage by careful observation of the video recording, in order to suggest safer procedures in laparoscopic surgery. Although these are only two LRN experiences, we are convinced that LRN can improve postoperative QOL (Quality of life) and is an acceptable alternative for the treatment of renal cell carcinomas.

Aged↗

[The C tube in biliary surgery--its development and clinical application].

BACKGROUND: The T tube procedure for bile drainage after biliary surgery has been used all over the world for more than 90 years. However, this method has serious drawbacks: a high complication ratio and a need for long-term hospitalization. Therefore other bile drainage methods including PTGBD, PTBD and ENBD have been developed, but none has so far been able to replace T tube. We have developed a new technique for bile drainage using the C tube (cystic duct tube), which is a slender tube (6Fr. polyvinyl) inserted via the cystic duct into the common bile duct (CBD). We have used C tube in more than 400 cases over the last 20 years: for open surgery during the first 10 years, and for laparoscopic surgery in the last 10 years. Here we describe the history of improvements in the C tube method and the techniques of C tube application in biliary surgery. Elastic surgical suture has been used to fix the C tube to the cystic duct, which successfully prevented bile leakage from the ductal stump after withdrawal of the tube. C tube is not only used for postoperative bile drainage but also for the management of remnant stones. The purpose of this study is to assess the safety and benefits of the C tube procedure. METHODS: I: From 1980 to 1998, 335 cholecystectomized cases which had undergone the C tube procedure were examined for complications resulting from C tube placement. II: We analyzed 134 patients with choledocholithiasis: 34 patients had been treated using C tube drainage, and 100 patients had been treated with the T tube procedure after undergoing CBD exploration. The main outcome criteria were: the frequency of post-operative complications, quantity of bile drainage, drainage period, and length of post-operative hospital stay. III: Between 1990 and 1999, 131 patients (15.2%) of a total of 860 laparoscopically cholecystectomized patients with gallstones underwent C tube treatment. We assessed the usefulness of the C tube procedure for the detection and management of remnant stones. RESULTS: I: There were no major complications (bile-leakage, CBD stenosis, etc.) in 335 cases which underwent the C tube procedure. Minor complications related to C tube were: spontaneous withdrawal of the tube in 5 cases, movement of the tube tip in 17 cases, and difficulties during tube removal in 32 cases which included slight resistance. Two cases had liver dysfunction (GOT 705 IU/l and 488 IU/l), although this was easily normalized after withdrawal of the tube tip from the duodenal papillae into the CBD. II: The frequency of complications in patients who underwent the C tube procedure was zero, whilst in the T tube group the major complication rate was 3% and the minor complication rate was 21%. The quantity of bile drainage was 283.6 +/- 22.9 ml/day in the C tube group compared with 302.7 +/- 10.3 ml/day in the T tube group, showing no significant difference. The drainage period (5.9 +/- 0.6 days) in the C tube group was significantly shorter than in the T tube group (27.7 +/- 0.9 days). Hospital stays (11.6 +/- 0.6 days) in the C tube group were significantly shorter than in the T tube group (45.0 +/- 1.5 days). III: Remnant CBD stones were detected by postoperative cholangiography via the C tube in 28 (21.4%) of the C tube replacement cases and in 3.3% of all the laparoscopically cholecystectomized patients. Seventeen patients with remnant stones were managed using glyceryl trinitrate CBD perfusion-induced relaxation of the sphincter of Oddi. The remaining patients were managed with endoscopic papillary balloon dilatation (EPBD) and/or endoscopic sphincterotomy (EST) without reoperation. We also have described other applications of the C tube procedure for the evaluation of sphincter of Oddi motility as an indication for EST, for bile drainage in liver resection, in the treatment of liver injuries, and for duodenal decompression after duodenal surgery. Finally we have mentioned the possibility of C tube application in the management of obstructive jaundice and bile drainage in liver transplantation surgery. CONCLUSION: The C tube method in biliary surgery is safe and useful in comparison with the T tube method. We are strongly convinced that the T tube will be completely replaced by the C tube.

Aged↗

Quantitative analysis of constitutive and inducible CYPs mRNA expression in the HepG2 cell line using reverse transcription-competitive PCR.

Drug interactions which affect drug metabolism are of clinical importance. It is, however, difficult to estimate drug interactions in human from results obtained in animal experiments. In our previous study, we demonstrated that a combination of the HepG2 cell line and semiquantitative reverse transcription-PCR (RT-PCR) could be used to evaluate the degree of CYP3A mRNA induction by various drugs. Using an RT-competitive PCR (RT-cPCR) with beta-actin as the standard in this study, the constitutive and rifampicin (RFP)-induced expression of CYP3A4, CYP2C9, CYP2E1, and CYP1A2 mRNA in the HepG2 cells could be quantitatively and reproducibly determined. 120 h-treatment of HepG2 cells with 50 micromol/l RFP induced maximally 8.4- and 6.0-fold the expression of CYP3A4 and CYP2C9 mRNA, respectively, in comparison with untreated cells. On the other hand, mRNA level in CYP2E1 and CYP1A2 was not significantly changed by 50 micromol/l RFP after 24 to 120 h. To our knowledge, we report for the first time quantitative profiles of CYPs mRNA in HepG2 cells. This study demonstrates the efficiency of a combination of HepG2 cells and RT-cPCR in the evaluation of CYPs mRNA-induction by drugs.

Aryl Hydrocarbon Hydroxylases↗

Synergism between interferon-gamma and cAMP in induction of hepatocyte growth factor in human skin fibroblasts.

Interferon (IFN)-gamma stimulates hepatocyte growth factor (HGF) production markedly in various human leukemia cell lines, but its positive effect in human skin fibroblasts is slight. We examined the combined effect of IFN-gamma and various HGF inducers on HGF production in human skin fibroblasts. IFN-gamma synergistically enhanced HGF production stimulated by 8-bromo-cAMP, one of the most effective inducers of HGF: HGF secreted from cells incubated with 1 mM of 8-bromo-cAMP, 1000 U/ml of IFN-gamma and both of these was approximately 8, 1.5 and 24 times, respectively, that secreted from untreated cells. The effect of IFN-gamma was dose-dependent and was nullified by an anti-IFN-gamma antibody. Neither IFN-alpha nor IFN-beta had such an enhancing effect, but both these IFNs inhibited the synergistic effect of IFN-gamma and 8-bromo-cAMP. IFN-gamma also synergistically augmented HGF production induced by interleukin-1beta and cAMP-increasing agents cholera toxin, forskolin and prostaglandin E(2). HGF gene expression upregulated by cholera toxin, forskolin and 8-bromo-cAMP was markedly enhanced by IFN-gamma, which was detected as early as 3 h after its addition. The synergy between HGF inducers and IFN-gamma is not common to all HGF inducers, because HGF production stimulated by epidermal growth factor and protein-kinase-C-activating phorbol esters was significantly inhibited by IFN-gamma. These results indicate that IFN-gamma synergistically stimulates cAMP-induced HGF production and inhibits HGF production induced by growth factors and protein kinase C activators in human skin fibroblasts.

8-Bromo Cyclic Adenosine Monophosphate↗

The impact of the CYP2D6 and CYP2C19 genotypes on venlafaxine pharmacokinetics in a Japanese population.

OBJECTIVE: The cytochrome P450 isozymes CYP2D6 and CYP2C19 exhibit genetic polymorphism in human, including a marked interethnic difference. As the functional status of the isozymes CYP2D6 and CYP2C19 have an impact on the pharmacokinetics of some antidepressants, we investigated whether the disposition of venlafaxine was affected by the CYP2D6 and CYP2C19 genotypes. METHODS: Twenty-eight adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and XbaI-RFLP analysis. Subjects were categorized into the following four groups: group 1 CYP2D6*10/*10; group 2 CYP2D6*1/*10 and *2/*10; group 3 CYP2D6*1/*1, *1/*2 and *2/*2; and group 4 the other genotypes. Two defective CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) were identified by means of PCR-RFLP analysis. Venlafaxine was administered orally following an overnight fast. Plasma concentrations of venlafaxine and O-desmethylvenlafaxine were monitored using high-performance liquid chromatography up to 24 h. RESULTS: The peak plasma concentration and values of area under the concentration-time curve up to 24 h for venlafaxine were 298% and 453% higher for group 1 than group 3, and 91% and 120% higher for group 2 than for group 3, respectively. The homozygote for two defective alleles of CYP2C19 showed a higher concentration of venlafaxine within group 1 and group 2. CONCLUSION: The CYP2D6*10 allele and two CYP2C19 defective alleles, common in an Asian population, are the most likely genetic factors to use in determining interindividual differences in the pharmacokinetics of venlafaxine, although the results with respect to CYP2C19 are preliminary because of the few subjects used.

Administration, Oral↗

Comparison of various biochemical measurements with bone mineral densitometry and quantitative ultrasound for the assessment of vertebral fracture.

We have retrospectively studied postmenopausal elderly Japanese women (n = 288; age range, 60-75 years, 65.8 +/- 4.5 [mean +/- SD]) for the evaluation of biochemical measurements in assessment of bone mass and vertebral fracture, comparing with several bone mineral measurements and quantitative ultrasound (QUS) measurement. Several biochemical parameters [red cell count (RBC), hemoglobin (HB), albumin (ALB), and cholesterol (CHO)] positively correlated with bone mass parameters, but only serum cholesterol showed association with the presence of vertebral fracture. Urinary deoxypyridinoline (DPYD) and n-telopeptide (NTx) showed moderate negative correlation with bone mass parameters, and DPYD showed association with vertebral fracture. All bone mineral measurements (lumbar spine, total body, femoral neck by DXA, calcaneal bone by SXA, distal radius by pQCT) and QUS measurement (os calcaneus by two different QUS machines) showed a higher odds ratio and high chi2 value in logistic regression analysis for association with vertebral fracture. Thus, bone mass measurement is the principal method for assessment of fracture risk, and biochemical measurement should be used for motivation of further bone mass measurement. In biochemical measurements, measurement of serum cholesterol is cheap and easy, and thus might have an advantage, although further study is necessary.

Absorptiometry, Photon↗

Successful closure of recurrent traumatic csf rhinorrhea using the free rectus abdominis muscle flap.

BACKGROUND: We present two patients in whom a free rectus abdominis muscle flap was used to close recurrent traumatic CSF rhinorrhea. CASE DESCRIPTION: CT scan of both patients showed frontal lobe atrophy and porencephaly after contusional hematoma. In the first patient, because the site of CSF leakage was not identified and the patient underwent three unsuccessful attempts to close the fistula using the fascia lata, we treated the patient by unifying all paranasal sinuses and by filling them with a free rectus abdominis muscle flap. In the second patient, CSF rhinorrhea recurred 6 years after closure of the fistula using the fascia lata. The patient underwent separation of a porencephalic cyst from the paranasal sinus and a free muscle flap was placed extradurally, because the CSF pulse pressure in the enlarged left anterior horn eroded the previously repaired fascia lata, resulting in the recurrence of CSF leakage. CONCLUSION: Although duraplasty is the primary procedure for repairing dural fistulas, the vascularized free muscle flap is an alternative method when the location of the fistula is not identified or the patient with recurrent CSF rhinorrhea has severe frontal lobe atrophy and porencephaly.

Adult↗

Study for verification testing of the helmet-mounted display in the Japanese Experimental Module.

Our purpose is to propose a research and development project in the field of telemedicine. The proposed Multimedia Telemedicine Experiment for Extra-Vehicular Activity will entail experiments designed to support astronaut health management during Extra-Vehicular Activity (EVA). Experiments will have relevant applications to the Japanese Experimental Module (JEM) operated by National Space Development Agency of Japan (NASDA) for the International Space Station (ISS). In essence, this is a proposal for verification testing of the Helmet-Mounted Display (HMD), which enables astronauts to verify their own blood pressures and electrocardiograms, and to view a display of instructions from the ground station and listings of work procedures. Specifically, HMD is a device designed to project images and data inside the astronaut's helmet. We consider this R&D proposal to be one of the most suitable projects under consideration in response to NASDA's open invitation calling for medical experiments to be conducted on JEM.

Data Display↗

Nitric oxide formation in the dog sphincter of Oddi from nitric oxide donors as measured with in vivo micro-dialysis.

BACKGROUND: Nitric oxide (NO) is known to play an important role in neurally mediated relaxation of the sphincter of Oddi. AIM: We investigated whether NO donors, such as nitroglycerin or zwitterionic polyamine/NO, applied into the common bile duct or intravenously, may induce the relaxation of the sphincter of Oddi by producing NO in the anaesthetized dog. METHODS: NO production in the sphincter of Oddi was measured by detecting NO oxidation products (NO2- and NO3-) using micro-dialysis methods. RESULTS: Zwitterionic polyamine/NO and nitroglycerin applied into the common bile duct induced a marked increase in NO2- but not NO3-, in the sphincter of Oddi. Intravenous infusion of zwitterionic polyamine/NO and nitroglycerin induced little or no increase in NO2- formation. Nitroglycerin infused into either the common bile duct or intravenously administered produced relaxation of the sphincter of Oddi, but zwitterionic polyamine/NO had no effect on the sphincter of Oddi in spite of the increase in NO2- levels. CONCLUSIONS: Locally or systemically applied NO donors induce relaxation of the sphincter of Oddi by producing NO, although their mode of action differs in different analogues.

Animals↗

Metabolism of a novel hypnotic, N3-phenacyluridine, and hypnotic and sedative activities of its enantiomer metabolites in mouse.

1. The metabolism of N3-phenacyluridine (3-phenacyl-1-beta-D-ribofuranosyluracil), a potent hypnotic nucleoside derivative, was studied in mouse. 2. Of the radioactivity, 65% was excreted in urine within 48 h after intraperitoneal (i.p.) administration of [3H]N3-phenacyluridine. The urinary metabolites N3-phenacyluracil and N3-alpha-hydroxy-beta-phenethyluridine were extracted, isolated and analyzed by mass spectrometry. 3. Racemates of N3-alpha-hydroxy-beta-phenethyluridine were synthesized and both isomers were separated as N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine by hplc (CHIRALCEL-OJ column) with retentions of 13.8 and 17.9 min respectively. The reduction process took place with high stereo-selectivity, which gave an alcohol product in the urine with the same retention (17.9 min) as one of the synthetic isomers separated by hplc. 4. One of urinary metabolites was identified as N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. N3-phenacyluridine was predominantly converted to an alcoholic metabolite of (S)-(+)-configuration. 5. N3-phenacyluracil and uridine were also identified as minor metabolites. 6. The pharmacological effects of the metabolites and related compounds were also evaluated in mouse. N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, possessed hypnotic activity and potentiated pentobarbital-induced sleeping time with a similar potency to the parent compound, N3-phenacyluridine. N3-alpha-hydroxy-beta-phenethyluridine (racemate) had almost two thirds of the hypnotic activity of N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. No other metabolites exhibited hypnotic activities. 7. The present study indicates that N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, a major metabolite of N3-phenacyluridine, is an active metabolite and contributes a significant CNS depressant effect.

Animals↗

Correlating the severity of paraquat poisoning with specific hemodynamic and oxygen metabolism variables.

OBJECTIVE: To investigate the hemodynamics and oxygen metabolism of patients with varying degrees of severity of paraquat poisoning. DESIGN: Prospective, observational, clinical study. SETTING: Intensive care unit in a university hospital. PATIENTS: Forty-three consecutive patients with paraquat and/or diquat poisoning were classified into three groups by the severity index of paraquat poisoning (SIPP; hr/mg/L). INTERVENTIONS: Standard treatments included specific respiratory management, fluid resuscitation, and aggressive circulatory support. MEASUREMENTS AND MAIN RESULTS: Serum paraquat and diquat levels were measured at arrival, and SIPP was calculated. The cardiac index (CI), left ventricular stroke work index (LVSWI), systemic vascular resistance index (SVRI), oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER) were measured at 6, 12, 24, 36, 48, 72, and 96 hrs postadmission. A significant inverse correlation between SIPP and survival time was found in 31 fatal cases (r = .85; p < .001). In the SIPP 10-50 group, CI, DO2I, VO2I, and O2ER were maintained at higher levels than in the SIPP group of <10 (p < .05), whereas SVRI decreased significantly (p < .05). In the SIPP group of >50, CI, LVSWI, SVRI, DO2I, and VO2I decreased, whereas O2ER had a tendency to increase progressively. There was a significant correlation between SVRI and SIPP, O2ER and SIPP, and O2ER and SVRI 24 hrs after admission, respectively (p < .001). CONCLUSIONS: Paraquat poisoning is characterized by high oxygen consumption with high oxygen extraction, with the degree of derangement based on the severity index. The development of a marked imbalance between increased oxygen demand and decreased oxygen supply because of myocardial depression might be a possible cause of death in circulatory failure.

Adolescent↗

Venous consideration in petrosal approach: microsurgical anatomy of the temporal bridging vein.

OBJECTIVE: The technical difficulty of using the petrosal approach and the likelihood of encountering venous complications depend on the particular temporal venous anatomy. To reduce such potential risks, neurosurgeons must have adequate knowledge of the variations in the anatomy of the temporal venous drainage system, particularly of the temporal bridging veins. METHODS: In 20 cadaveric specimens, the temporal bridging veins were examined with the aid of an operating microscope. The anatomic location of their termination and of the tributaries of these bridging veins was noted. RESULTS: Forty-four terminations and 109 tributaries of the temporal bridging veins were identified in our specimens. The temporal bridging veins were divided into three groups according to the anatomic location of their terminations: 1) the transverse sinus group (seen in all 20 hemispheres), with drainage into the lateral part of the cerebellar tentorium, to which most of the vein of Labbé belongs; 2) the tentorial group (seen in 50% of the 20 hemispheres), with drainage into the medial part of the tentorium, which is composed mainly of the middle and posterior temporobasal veins; and 3) the petrosal group (seen in 55% of the 20 hemispheres), with entry around the superior petrosal sinus, which may limit mobility of the temporal lobe in the petrosal approach. On the basis of this anatomic information, we propose a new classification of the temporal venous drainage system and discuss the clinical implications of these findings. CONCLUSION: In planning the petrosal approach, great care should be taken not only with the vein of Labbé but also with the petrosal bridging veins. Knowledge of this venous anatomy can reduce venous complications during the lateral cranial base approach.

Cadaver↗

FDG PET in the evaluation of the aggressiveness of pulmonary adenocarcinoma: correlation with histopathological features.

2-[Fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake within the primary lesion correlates with survival on positron emission tomography (PET) studies of patients with non-small cell lung cancer. The more metabolically active the tumour, the worse the outcome. The aim of this study was to determine whether a correlation exists between aggressiveness as determined by pathology and the findings of FDG PET in pulmonary adenocarcinoma. Thirty-five patients with 38 adenocarcinomas of the lung were studied. All patients underwent thoracotomy within 4 weeks of the FDG PET study. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high SUV (> or = 4.0) and low SUV (<4.0) groups. The degree of FDG uptake (SUVs) in primary lung lesions was correlated with the histopathological features of aggressiveness (pleural involvement, vascular invasion or lymphatic permeation). The mean SUV of aggressive adenocarcinomas (4.36+/-1.94, n = 22) was higher than that of non-aggressive ones (1.53+/-0.88, n = 16) (P < 0.0001). Tumours with a high FDG uptake have a significantly higher likelihood of aggressiveness than those with a low FDG uptake (P = 0.0004). Analysis by the Kaplan-Meier methods revealed that the groups had different prognoses (log-rank test, P = 0.0099). The high SUV group had a significantly worse prognosis. In conclusion, a correlation was seen between aggressiveness as determined by pathology and glucose metabolism as measured by FDG PET in adenocarcinoma of the lung. FDG PET may be used as a non-invasive diagnostic technique in measuring aggressiveness and prognosis in patients with pulmonary adenocarcinoma.

Adenocarcinoma↗