PubMed Health⌕ Search

Biomedical subjects

A Nagashima

Publications and source records attributed to A Nagashima.

At least 19 recordsLinked to original sources
PubMed2005

A study of the in vitro interaction between lidocaine and premedications using human liver microsomes.

OBJECTIVE: To investigate potential interactions between lidocaine (lignocaine) metabolism and premedication drugs, i.e. psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing neuromuscular blocking agents (vecuronium, pancuronium and suxamethonium), an antihypertensive agent (clonidine) and an H2-receptor blocking agent (cimetidine) using human liver microsomes in vitro. METHODS: The interaction effects between lidocaine and premedication were examined using human liver microsomal preparations and monitored for enzyme activity. The lidocaine and its main metabolite (monoethylglycinexylide) were measured by HPLC/UV. RESULTS: Lidocaine metabolism was non-competitively inhibited by midazolam (Ki = 77.6 microM). Thiamylal was a competitive inhibitor of lidocaine metabolism (Ki = 885 microM). Cimethidine, pancuronium and vecuronium weakly inhibited lidocaine metabolism in a concentration-depend manner over the therapeutic range in human liver microsomes. On the contrary, suxamethonium, pentobarbital and clonidine did not inhibit lidocaine metabolism over the therapeutic range in human liver microsomes. CONCLUSION: These results show that the interactions between lidocaine and midazolam and thiamylal are of potential toxicological and clinical significance.

Animals↗
PubMed2002

A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes.

In this study, we have investigated the relationship between lidocaine metabolism and premedication, i.e., psychotropic and anti-anxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing muscular relaxants (vecuronium, pancuronium and suxamethonium), an active anti-hypertensive (clonidine) and an H2 receptor antagonist (cimetidine) using rat hepatic microsomes in vitro. Lidocaine metabolism was noncompetitively inhibited by midazolam (Ki=29.0 microM). Thilamylal was a moderate competitive inhibitor of lidocaine metabolism (Ki=77.8 microM). Pentobarbital, diazepam and cimetidine weakly inhibited lidocaine metabolism formation in a concentration-dependent manner at high substrate concentrations. On the other hand, vecuronium, pancuronium, suxamethonium and clonidine did not inhibit lidocaine metabolism over the therapeutic range. These results show that the interaction between lidocaine and midazolam and thiamylal, catalyzed by a similar cytochrome P450, is of potential importance in toxicological and clinical studies.

Anesthetics, Local↗
PubMed2001

FR226807: a potent and selective phosphodiesterase type 5 inhibitor.

We describe the pharmacological characteristics of a novel phosphodiesterase type 5 inhibitor FR226807, N-(3,4-dimethoxybenzyl)-2-[[(1R)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide. FR226807 inhibited phosphodiesterase type 5 isolated from human platelets with an IC(50) value of 1.1 nM. FR226807 also inhibited phosphodiesterase type 6 with an IC(50) of 20 nM; however, the IC(50) value for phosphodiesterase type 6 was 18-fold higher than that for phosphodiesterase type 5. The IC(50) values of FR226807 for other phosphodiesterases (phosphodiesterase type 1, phosphodiesterase type 2, phosphodiesterase type 3, and phosphodiesterase type 4) were 1000-fold higher than that for phosphodiesterase type 5. FR226807 increased the cyclic guanosine monophosphate (cGMP) content in corpus cavernosum isolated from rabbit, an effect associated with relaxation of the muscle. FR226807 enhanced the relaxation response induced by electrical field stimulation of corpus cavernosum isolated from the rabbit. In an anesthetized dog model for the evaluation of erectile function, intravenous administration of FR226807 prolonged the time to return to 75% of maximal intracavernosal pressure after cessation of electrical stimulation of the pelvic nerve. In summary, FR226807 is a potent and highly selective phosphodiesterase type 5 inhibitor with an augmentative effect on penile erection and will be useful for the treatment of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Determination of plasma bromvalerylurea and its main metabolite by a simple high-performance liquid chromatographic method and quantitation of bromide by energy dispersive X-ray spectrometry in carbon tetrachloride-intoxicated rats.

In the present study, small volumes of plasma were used for the measurement of bromvalerylurea (BVU), its metabolite, 3-methylbutyrylurea (MVU), and bromide in carbon tetrachloride (CCl4)-treated rats by HPLC-UV and energy dispersive X-ray spectrometry. A liquid-liquid extraction system was also investigated. BVU and MVU were extracted from 100 microl plasma samples in a single-step involving deproteination with 1 M hydrochloric acid using ethenzamide as internal standard. Samples were separated by HPLC in an acetonitrile-8 mM potassium dihydrogenphosphate buffer (35:65, v/v) mobile phase at a flow-rate of 0.4 ml/min on a 15 cm octadecylsilyl column at room temperature. Analytes were detected at a wavelength of 210 nm. The limits of quantitation for BVU, MVU and bromide are 0.1, 0.1 and 50 microg/ml, respectively. The intra-day accuracies over the range of concentrations were 95.8 to 121.1%, 97.2 to 119.7% and 96.2 to 105.8% for BVU, MVU and bromide, respectively. The inter-day accuracies were 97.7 to 115.1%, 98.3 to 111.6% and 98.3 to 102.9% for BVU, MVU and bromide, respectively. The absolute recoveries using tert.-butyl methyl ether are 96-98% for BVU and 95-98% for MVU. The decline in the plasma concentrations of BVU in olive oil-treated rats fitted a one-compartment model and the plasma MVU level reached a peak at around 1.5-2 h and then decreased gradually. The elimination of BVU in CCl4 (1 ml/kg)-treated rats was delayed and MVU production was less than that in the olive oil-treated group. However, there was no difference in the plasma levels of bromide between CCl4-treated rats and control rats. rights reserved.

Animals↗
PubMed2001

Prolonged survival of mouse epididymal spermatozoa stored at room temperature.

The viability and fertility of isolated mouse epididymal spermatozoa kept for up to 7 days at various temperatures (4 degrees C, 22 degrees C, and 37 degrees C) were determined. Spermatozoa kept for 3 days at 22 degrees C were still active, while those kept at 37 degrees C or 4 degrees C exhibited great reduction in motility within 2 days after isolation. In vitro fertilizing abilities of spermatozoa left for 0, 1, 2, and 3 days at 22 degrees C were 69.2, 32.5, 9.5, and 4.9%, respectively, when the cleavage rate to two-cell stage was examined. Transfer of two-cell embryos produced in vitro with spermatozoa left for 1, 2, and 3 days at 22 degrees C resulted in production of fetuses with efficiencies of respectively 30.2, 11.5, and 16.7%, which were lower (63.3%) than that of embryos derived from in vitro fertilization with fresh spermatozoa. These findings indicate that spermatozoa kept for up to 3 days at 22 degrees C can fertilize oocytes, although at relatively low efficiency.

Animals↗
PubMed2001

Usefulness of double gene construct for rapid identification of transgenic mice exhibiting tissue-specific gene expression.

Identification of transgenics still requires PCR and genomic Southern blot hybridization of genomic DNA isolated from tail pieces. Furthermore, identification of transgene-expressing transgenics (hereafter called "expressor") requires mRNA analyses (RT-PCR and Northern blot hybridization) or protein analysis (Western blotting and immunohistochemical staining using specific antibodies). These approaches are often labor-intensive and time-consuming. We developed a technique that simplifies the process of screening expressor transgenics using enhanced green fluorescent protein (EGFP), a noninvasive reporter recently utilized in a variety of organisms, including mice, as a tag. We constructed a MNCE transgene consisting of two expression units, MBP-NCre (termed "MN") and CAG-EGFP (termed "CE"). MN consists of a myelin basic protein (MBP) promoter and NCre gene (Cre gene carrying a nuclear localization signal (NLS) sequence at its 5' end). CE consists of a promoter element, CAG composed of cytomegalovirus (CMV) enhancer and chicken beta-actin promoter, and EGFP cDNA. Of a total of 72 F0 mice obtained after pronuclear injection of MNCE at 1-cell egg stage, 15 were found to express EGFP when the tail, eye, and inner surface of the ear were inspected for EGFP fluorescence under UV illumination at weaning stage. These fluorescent mice were found to possess MNCE and to express NCre mRNA in a brain-specific manner. Mice exhibiting no fluorescence were transgenic or nontransgenic. Mice carrying MNCE, but exhibiting no fluorescence, never expressed NCre mRNA in any organs tested. These findings indicate that (i) direct inspection of the surface of mice for fluorescence under UV illumination enables identification of expressor transgenics without performances of the molecular biological analyses mentioned above, and (ii) systemic promoters such as CAG do not affect the tissue-specificity of a tissue-specific promoter such as MBP promoter, which is located upstream of CAG by approximately 2 kb.

Actins↗
PubMed2001

An Arabidopsis sigma factor (SIG2)-dependent expression of plastid-encoded tRNAs in chloroplasts.

A eubacteria-type RNA polymerase (PEP) plays crucial roles for chloroplast development in higher plants. The core subunits are encoded on plastid DNA (rpo genes) while the regulatory sigma factors are encoded on the nuclear DNA (SIG genes). However, the definite gene specificity of each sigma factor is unknown. We recently identified an Arabidopsis recessive pale-green mutant abc1 in which T-DNA is inserted in SIG2 (sigB). In this mutant, almost normal etioplasts were developed under dark conditions while the small chloroplasts with poor thylakoid membranes and stacked lamellar were developed under light conditions. The sig2-1 mutant was deficient in accumulating enough photosynthetic and photosynthesis-related proteins as well as chlorophyll. However, mRNAs of their structural genes were not significantly reduced. Further analyses revealed that several plastid-encoded tRNAs including trnE-UUC that has dual function for protein and ALA biosyntheses were drastically reduced in the sig2-1 mutant. In contrast, nucleus-encoded T7 phage-type RNA polymerase (NEP)-dependent gene transcripts were steadily accumulated in the mutant. These results indicate that progress of chloroplast development requires SIG2-dependent expression of plastid genes, particularly some of the tRNA genes.

Arabidopsis↗
PubMed2001

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

UNLABELLED: There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. IMPLICATIONS: Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.

Administration, Oral↗
PubMed2001

Successful induction of tumor-specific cytotoxic T lymphocytes from patients with non-small cell lung cancer using CD80-transfected autologous tumor cells.

Cytotoxic T lymphocytes (CTL) against human lung cancer cells are difficult to induce by a conventional method using tumor cell stimulation probably due to an insufficiency of tumor antigens (TA) or costimulatory molecules such as CD80. We, therefore, investigated the potential of CD80-transfected tumor cells as stimulators of the in vitro induction of autologous tumor-specific CTL from regional lymph node lymphocytes in patients with lung cancer. Five non-small cell lung cancer cell lines (two adenocarcinomas, 1 squamous cell carcinoma, 1 large cell carcinoma and 1 adenosquamous cell carcinoma) were established from surgical specimens and were successfully transduced with a plasmid constructed with expression vector pBj and human CD80 cDNA, using a lipofection method. CD80-transfected tumor cells (CD80-AT) significantly augmented the proliferation of autologous lymphocytes from all cases as compared with non-transfected tumor cells (AT). AT-stimulated lymphocytes from 4 out of 5 cases did not show any cytotoxicity against AT; however, lymphocytes stimulated with CD80-AT exhibited substantial cytotoxicity against parental AT in all 5 cases tested. AT-stimulated lymphocytes derived from only one out of 5 cases showed major histocompatibility complex (MHC)-class I-restricted cytokine production in response to AT, while the MHC-class I-restricted responses were found in CD80-AT-stimulated lymphocytes from 4 out of 5 cases. These results indicate that CD80 on tumor cells could be a beneficial costimulatory molecule to elicit CTL against lung cancer, and also show that TA recognized by CTL was frequently expressed on lung cancer cells.

Adenocarcinoma↗
PubMed2000

Three new nuclear genes, sigD, sigE and sigF, encoding putative plastid RNA polymerase sigma factors in Aarabidopsis thaliana.

Three new nuclear genes (sigD, sigE and sigF) of Arabidopsis thaliana, encoding putative plastid RNA polymerase sigma factors, were identified and analyzed. Phylogenetic analysis revealed that higher plant sigma factors fell into at least four distinct subgroups within a diverse protein family. In addition, Arabidopsis sig genes contained conserved chromosomal intron sites, indicating that these genes arose by DNA duplication events during plant evolution. Transcript analyses revealed two alternatively spliced transcripts generated from the sigD region, one of which is predicted to encode a sigma protein lacking the carboxy-terminal regions 3 and 4. Finally, the amino-terminal sequence of the sigF gene product was shown to function as a plastid-targeting signal using green fluorescent protein fusions.

Alternative Splicing↗
PubMed2000

Pericardial cyst in a child treated with video-assisted thoracoscopic surgery.

UNLABELLED: A pericardial cyst is a rare condition in childhood. We report on a 10-year-old girl who presented with an intrathoracic mass detected on a chest X-ray performed during a routine medical examination. She had no symptoms and a physical examination revealed no abnormalities. Ultrasonography, computed tomography and magnetic resonance imaging showed a multiloculated cystic mass in the right upper thorax. The cyst was resected using a thoracoscopic procedure. Histologically, the findings were consistent with a pericardial cyst. Thoracoscopic surgery was an effective surgical technique even for such a young patient and the results successfully reduced the morbidity. CONCLUSION: A pericardial cyst, a rare condition in childhood, was treated successfully by video-assisted thoracoscopic surgery.

Child↗
PubMed2000

Bone metastasis after a resection of stage I and II primary lung cancer.

In the present study, we reviewed the patients who developed bone metastases after a surgical resection of primary lung cancer and evaluated their clinicopathological features. From 1992 to 1995, 177 patients with stage I and II primary lung cancer underwent a surgical resection at the Kitakyushu Municipal Medical Center. Bone metastases were detected in 14 patients (7.9%) by follow-up examinations including bone scintigraphy (scan). Bone metastasis was one of the most frequent extra-thoracic recurrent forms. Patients with adenocarcinoma tended to develop bone metastases more frequently than those with squamous cell carcinoma. In the preoperative bone scans, an abnormal uptake was observed in 76 patients (42.9%), and 10 (13.1%) of them were found to develop bone metastases in the follow-up studies. A microscopic examination of the primary tumor demonstrated close correlation between intratumoral and peritumoral lymphatic vessel invasion and postoperative development of bone metastases. A bone scan is a very useful and indispensable procedure for diagnosing bone metastases. However, this scan may also show false positive finding in a number of benign conditions. Therefore, a surgical resection should be considered as the first-line treatment for patients with positive findings in the bone scan when the diagnosis of bone metastasis can not be confirmed based on both their symptoms and other clinical examinations.

Adenocarcinoma↗
PubMed2000

Chloroplast targeting, distribution and transcriptional fluctuation of AtMinD1, a Eubacteria-type factor critical for chloroplast division.

In Arabidopsis thaliana, a mature mesophyll cell contains approximately 100 chloroplasts. Although 12 arc mutants (accumulation and replication of chloroplasts) and two chloroplast division genes homologous to eubacterial ftsZ have been isolated from A. thaliana, the molecular mechanism underlying the chloroplast division is still unclear. We characterized AtMinD1, a eubacterial minD homolog, for chloroplast division in A. thaliana. AtMinD1-green fluorescent protein targeted to the chloroplasts and possibly associated with the envelope membranes in vivo. During the seed germination, the AtMinD1 transcripts were accumulated twice, just after release from cold treatment and at the beginning of rapid greening, in similar fashion to AtFtsZs. Furthermore the transcript level in a severest chloroplast division mutant, arc6, was 3-5-fold higher than that in wild-type.

Amino Acid Sequence↗
PubMed2000

Chronic intestinal pseudo-obstruction due to dialysis-related amyloid deposition in the propria muscularis in a hemodialysis patient.

Dialysis-related amyloidosis (DRA) is one of the most serious complications interfering with rehabilitation in dialysis patients. Here, we report a case of beta2-microglobulin (beta2M)-related amyloidosis, in which the patient developed a severe intestinal pseudo-obstruction. The patient was a 42-year-old male who had been undergoing hemodialysis for 13 years, and who had no history of osteoarticular involvement of DRA. The first symptoms of the disease were severe abdominal fullness and nausea after meals. The whole intestinal wall biopsy revealed massive amyloid deposition in the propria muscularis. The patient became malnourished and died of acute subendocardial infarction 3 years after the onset. An autopsical examination revealed a massive deposition of amyloid, which was positively stained with anti-beta2M antibody but not AA amyloid, predominantly in the gastrointestinal muscular layer, including the tongue, esophagus, stomach, small intestines, colon, and rectum. These results suggest that the gastrointestinal involvement of beta2M-related amyloidosis might occur during the course of hemodialysis treatment, and that this possibility should be considered if patients suffer from intestinal pseudo-obstruction without osteoarticular symptoms.

Adult↗
PubMed1999

Stomal recurrence invading the cervicothoracic esophagus and upper mediastinum: resectability and the creation of a safe anterior mediastinal tracheostoma.

Surgical salvage for stomal recurrence is a for midable problem for head and neck surgeons. The two factors of considerable significance are resectability and establishment of a safe anterior mediastinal tracheostoma. A case of stomal recurrence invading the cervicothoracic esophagus and upper mediastinum is presented. Total esophagectomy and upper mediastinal dissection was performed. The esophagus was reconstructed immediately with a pedicled gastric flap. The omentum on the gastric pedicle was wrapped around the trachea to reduce the likelihood of erosion into the great vessels and to supplement the lateral blood supply to the trachea. No serious postoperative complications were observed. We believe that the total esophagectomy improved the resectability, and that the bulk of the gastric pedicle and the use of the omentum prevented significant postoperative complications associated with an anterior mediastinal tracheostoma.

Anastomosis, Surgical↗
PubMed1999

Results of surgical treatment of lung cancer in octogenarians.

The treatment of potentially resectable lung cancer in octogenarians has become a frequent clinical problem, due to the increasing number of elderly people maintaining an active daily life. In the present study, we reviewed the clinical records of patients to evaluate the results of the surgical treatment of lung cancer in octogenarians. From 1992 to 1995, 18 patients aged 80 years or older (octogenarians) with primary lung cancer underwent surgical resections including: three (16.7%) sleeve lobectomies, nine (50.0%) lobectomies, one (5.5%) segmentectomy, and five (27.8%) partial resections. The postoperative complication rate was 50% in octogenarians; however, no fatal complications were observed. The 5-year survival rate was 42.6%, which was similar to that obtained in younger patients. Based on our findings, the surgical treatment of lung cancer can thus be performed in selected octogenarians without increasing either morbidity or mortality, while also obtaining long-term survival.

Adolescent↗