Search PubMed⌕ Search

Biomedical subjects

A Yamamoto

Publications and source records attributed to A Yamamoto.

At least 145 records · Page 8Linked to original sources
PubMed2001

Evaluation of insulin permeability and effects of absorption enhancers on its permeability by an in vitro pulmonary epithelial system using Xenopus pulmonary membrane.

The permeability of insulin across Xenopus pulmonary membrane and the effects of various absorption enhancers on insulin permeability were examined using an in vitro Ussing chamber technique. Absorption enhancers used in this study were sodium caprate (NaCap), sodium glycocholate (NaGC), sodium salicylate (NaSal) and ethylenediaminetetraacetic acid disodium salt (EDTA). The permeability of insulin across Xenopus pulmonary membrane significantly increased in the presence of NaCap and NaGC, while EDTA and NaSal did not enhance the permeability. In addition, the enhancing effect of NaGC increased as the concentrations of these enhancers increased. Transmembrane resistance (Rm) of Xenopus lung was markedly decreased in the presence of these enhancers, and NaCap showed a greater effect on Rm than NaGC. Furthermore, the amount of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) released from the apical side of the Xenopus pulmonary membrane increased in the presence of these enhancers. These results indicate that NaCap and NaGC improve the pulmonary absorption of insulin, but they are toxic to the pulmonary membrane. These findings suggest that this method is useful for estimating the permeability characteristics of peptides across the pulmonary membrane and for evaluating the effects of various additives on their permeability and their membrane toxicity.

Absorption↗
PubMed2001

Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats.

Effects of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, simvastatin and atorvastatin, on diltiazem-induced hypotension were examined in anaesthetized rats and compared to that of pravastatin. Vehicle, 2 mg/kg/day simvastatin, 2 mg/kg/day atorvastatin, or 4 mg/kg/day pravastatin was administered orally for 4 days. Diltiazem at 3 mg/kg was given orally 2 hours after the final administration of the inhibitors. Arterial blood pressure was measured via a cannula introduced into the left carotid artery, and heart rate was counted from the pulse pressure. In all groups, diltiazem significantly decreased the mean arterial blood pressure without any changes in heart rate. Pretreatment with simvastatin and atorvastatin significantly enhanced the hypotensive effect of diltiazem, while that with pravastatin did not. Heart rate was not modified by pretreatment with the inhibitors. The results indicate that concomitant use of diltiazem with simvastatin or atorvastatin enhances diltiazem-induced hypotension, probably by competitive inhibition of diltiazem metabolism with simvastatin and atorvastatin metabolisms.

Animals↗
PubMed2001

[Improvement of transmucosal absorption of biologically active peptide drugs].

Peptide and protein drugs are becoming a very important class of therapeutic agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract or impermeable through the intestinal mucosa. For the systemic delivery of the peptide and protein drugs, parenteral administration is currently required to achieve their therapeutic activities. However, this administration is poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various approaches have been examined to overcome the delivery problems of these peptides when they are administered into the gastrointestinal tract and other mucosal sites. These approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides that can serve as an alternative to oral and injection administration, (3) to modify the molecular structure of peptide and protein drugs to produce prodrugs and analogues, and (4) to use the dosage forms to these peptide drugs. In this study, we demonstrated that the transmucosal absorption of various peptides including insulin, calcitonin, tetragastrin and thyrotropin releasing hormone (TRH) could be improved by the use of these approaches. Therefore, these approaches may give us basic information to improve the transmucosal absorption of peptide and protein drugs.

Animals↗
PubMed2001

Validity and reliability of single-item questions about physical activity.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study) included in its self-administered questionnaires some single-item questions concerning physical activity. We examined the validity of the questions among 1,730 Japanese adults and the reliability of the questions among 1,075 Japanese adults. The validity of the sports and physical exercise questions was estimated by comparing the self-administered questionnaire responses with the time spent on the activity and the energy expenditure index for the previous 12-month period, elicited by the interviewing method used in the Japan Lifestyle Monitoring Study with a minor modification. The Spearman's rank correlation coefficients ranged from 0.43 to 0.60, showing moderate correlations. On the other hand, test-retest reliability was estimated by comparing the responses from two separate surveys conducted roughly one year apart. Weighted kappa coefficients of sports and physical exercise questions, classified according to sex and age, ranged from 0.39 to 0.56, showing moderate reliability; and those of a question about walking ranged from 0.25 to 0.39, showing fair reliability. We suggest that measuring physical activity level with these single-item questions may be appropriate for establishing baseline data that reflects long-term physical activity in a large-scale cohort study targeting lifestyle-related diseases.

Adult↗
PubMed2001

Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells.

Pancreatic islet cells express receptors and transporters for L-glutamate and are thus believed to use L-glutamate as an intercellular signaling molecule. However, the mechanism by which L-glutamate appears in the islets is unknown. In the present study, we investigated whether L-glutamate is secreted through exocytosis by alphaTC6 cells (clonal mouse pancreatic alpha-cells). An appreciable amount of L-glutamate was released from cultured cells after the addition of KCl or A23187 in the presence of Ca2+ and 10 mmol/l glucose in the medium. The KCl-induced glutamate release was significantly reduced when assayed in the absence of Ca2+ or when the cells were pretreated with EGTA-AM. The KCl-induced Ca2+-dependent glutamate release was inhibited approximately 40% by voltage-gated Ca2+ channel blockers, such as nifedipine at 20 micromol/l. The degree of KCl-induced Ca2+-dependent glutamate release was correlated with an increase in intracellular [Ca2+], as monitored by fura-2 fluorescence. Botulinum neurotoxin type E inhibited 55% of the KCl-induced Ca2+-dependent glutamate release, followed by specific cleavage of 25 kDa synaptosomal-associated protein. Furthermore, bafilomycin A1, a specific inhibitor of vacuolar H+-ATPase, inhibited 40% of the KCl-induced Ca2+-dependent glutamate release. Immunoelectronmicroscopy with antibodies against synaptophysin, a marker for neuronal synaptic vesicles and endocrine synaptic-like microvesicles, revealed a large number of synaptophysin-positive clear vesicles in cells. Digitonin-permeabilized cells took up L-glutamate only in the presence of MgATP, which is sensitive to bafilomycin A1 or 3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (a proton conductor) but insensitive to either oligomycin or vanadate. From these results, it was concluded that alphaTC6 cells accumulate L-glutamate in the synaptophysin-containing vesicles in an ATP-dependent manner and secrete it through a Ca2+-dependent exocytic mechanism. The Ca2+-dependent glutamate release was also triggered when cells were transferred in the medium containing 1 mmol/l glucose, suggesting that low glucose treatment stimulates the release of glutamate. Our results are consistent with the idea that L-glutamate is secreted by alpha-cells through Ca2+-dependent regulated exocytosis.

Adenosine Triphosphate↗
PubMed2001

Vascular reconstruction of a vertebral artery loop causing cervical radiculopathy and vertebrobasilar insufficiency. Case report.

The authors present the case of a 62-year-old man with a 4-month history of progressive left-sided C-5 radiculopathy and dizziness. Neuroimaging studies revealed a looped vertebral artery (VA) that had migrated into the widened left C4-5 intervertebral foramen. The patient underwent vascular reconstruction of the VA loop, in which there was minimal manipulation of the C-5 nerve root, via a left-sided anterolateral approach after a balloon occlusion test. Postoperatively the patient's symptoms improved immediately, and there were no signs of recurrence within the 2-year follow-up period. This excellent outcome supports the belief that a proper surgical reconstruction of the compressive, tortuous VA should be the therapeutic option of choice, which carries a lower risk of the nerve root injury and improves the hemodynamics in the posterior circulation.

Angiography↗
PubMed2001

[Treatment of phimosis with betamethasone ointment in children].

OBJECTIVE: We evaluated the efficacy of betamethasone ointment in the treatment of childhood phimosis and determined the most effective concentration of betamethasone. MATERIAL AND METHODS: Between August 1996 and May 2000, 69 patients (median age 3.0, range 0-12) presented to our department with severe phimosis (grade 4, Tsugaya's classification), and were enrolled in this study and treated with betamethasone ointment for 4 weeks. The ointment was applied on the narrowed preputial skin twice a day by parents. During the first week, parents were asked not to retract the foreskin. After this period, parents were encouraged to retract the foreskin gently and without intense tension. The concentration of betamethasone were 0.12%, 0.05% and 0.025%. If the patients become to be able to retract foreskin satisfactory, we consider the state as complete response. If he become to be able to retract to allow partial exposure of the glans, we consider the state as partial response. We compared the efficacy among each of the concentrations, and at 3 months after the end of the treatment, we also assessed the adverse effects and recurrence. RESULTS: The overall success rate was 85.5%. Success rates with 0.12%, 0.05% and 0.025% ointment were 96.8%, 82.8% and 55.6%, respectively (p = 0.0001). The 0.12% ointment was most effective. Recurrence was observed in 3 patients (4.3%). No adverse effects were observed in any of the patients. CONCLUSIONS: Treatment with betamethasone ointment is very effective, easy and safe. We recommend betamethasone ointment as the first treatment of choice for childhood phimosis.

Betamethasone↗
PubMed2001

[Comparison of digital subtraction angiography, CT angiography, and ultrasonic Doppler examination in the evaluation of penile arterial lesions].

BACKGROUND: CT angiography reconstructed by a multidetector-row helical CT scanner is a newly developed form of imaging. We compared CT angiography and ultrasonic Doppler examination with digital subtraction angiography (DSA) in the diagnosis of arterial lesion. METHOD: Eighteen patients with arteriogenic erectile dysfunction (ED) underwent color Doppler study, DSA, and CT angiography after providing informed consent. The CT angiography images were obtained by a multidetector-row helical CT scanner, Asteion TSX021A (TOSHIBA). We injected prostaglandin E1 into the penile cavernous body, and then rapidly infused nonionic contrast medium into the antecubital vein. DSA and CT angiography images of the bilateral internal pudendal arteries and cavernous arteries were examined for stenotic lesions or occlusion. We also compared the peak systolic blood flow velocity in the cavernous artery measured by color Doppler ultrasound with CT angiography and DSA. RESULTS: The CT angiography and color Doppler studies were performed on an outpatient basis, but DSA required hospitalization. In the 36 internal pudendal arteries, DSA represented 22 normal arteries and 14 stenosis or occlusions. CT angiography showed 15 normal arteries and 21 occlusions. For the diagnosis of stenosis or occlusion in the internal pudendal artery, the CT angiography image had a good agreement, with a sensitivity of 1.00, specificity of 0.68, and accuracy of 0.81. For diagnosis in the cavernous artery, CT angiography image also showed a good agreement with DSA; however, the quality of the images of fine arteries was better in the DSA images. The inferior view and internal view of the pelvis in CT angiography were helpful for visualizing the internal pudendal artery, especially at the pubic bone. There was insufficient correlation between peak systolic blood flow velocity and DSA findings. There were no serious complications involved in either examination. CONCLUSIONS: CT angiography has not yet reached the same level as DSA in the evaluation of fine arteries. However, CT angiography can produced images sufficient for the diagnosis of arteriogenic ED with some advantages. We believe that with improvement, CT angiography will become an adequate replacement for DSA in the diagnosis of penile arterisl lesion.

Adult↗
PubMed2001

FR167653, a p38 mitogen-activated protein kinase inhibitor, prevents Helicobacter pylori-induced gastritis in Mongolian gerbils.

FR167653 was discovered as a cytokine production inhibitor, but its target molecule has remained unclear. We examined the effect of FR167653 on activities of purified protein kinases. FR167653 dose dependently inhibited p38alpha mitogen-activated protein kinase activity without affecting the activities of other kinases. FR167653 had no effect on cyclooxygenase (COX)-1 or COX-2 activities, whereas SB203580 inhibited them. FR167653 suppressed endogenous p38 kinase activity in interleukin-1-stimulated NRK-F cells. These results indicate that FR167653 is a p38 kinase-selective inhibitor without affecting COX activity. To evaluate the role of p38 kinase in Helicobacter pylori gastritis, we therefore examined the effect of FR167653 on H. pylori-induced gastritis in Mongolian gerbils. H. pylori infection activated p38 kinase in the gastric mucosa and caused neutrophil infiltration from 2 and 3 weeks of infection, respectively. At 4 weeks, severe mucosal inflammation with erosive injury was observed. When FR167653 was administered to H. pylori-infected gerbils from 2 weeks, both neutrophil infiltration and mucosal injury at 4 weeks were significantly prevented. FR167653 markedly reduced the H. pylori-induced increase in endogenous p38 kinase activity in the gastric mucosa, and also significantly inhibited neutrophil chemokine production. In contrast, the drug did not affect H. pylori colonization or acid secretion. FR167653 did not cause any pathological change in the gastric mucosa of normal animals. These results indicate that p38 kinase plays a crucial role in H. pylori-induced gastritis in Mongolian gerbils.

Animals↗
PubMed2001

Modulation of intestinal permeability by nitric oxide donors: implications in intestinal delivery of poorly absorbable drugs.

The effects of nitric oxide (NO) donors NOC5 [3-(2-hydroxy-1-(methylethyl)-2-nitrosohydrazino)-1-propanamine ] and NOC12 [N-ethyl-2-(1-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine] on the permeability of 5(6)-carboxyfluorescein (CF) across the intestinal membrane were examined by an in vitro Ussing chamber method. The NO donors significantly increased the intestinal permeability of CF and their absorption-enhancing effects were concentration-dependent over the range of 0.01 to 0.1 mM. Regional differences in the absorption-enhancing effects of the NO donors were observed (colon > jejunum). The absorption-enhancing effect of NOC12 reduced as the molecular weights of compounds increased. Therefore, the degree of absorption-enhancing effect of NOC12 was dependent on the molecular weights of compounds. In the pretreatment studies with NOC12 and lactate dehydrogenase release studies, the absorption-enhancing effect of 0.1 mM NOC12 was reversible and less toxic to the colonic membrane. On the other hand, the absorption-enhancing effect of NOC12 was inhibited by the coadministration of 2-(4-carboxyphenyl) 4,4,5, 5-tetramethylimidazole-1-oxyl 3-oxide sodium salt, an NO scavenger, suggesting that NO can regulate the permeability of water-soluble drugs in the gut. Furthermore, NOC12 (0.1 and 1 mM) significantly decreased the transepithelial electrical resistance value of the colonic membrane, suggesting that the absorption-enhancing mechanism of NOC12 may be partly related to the dilation of the tight junction in the epithelium via a paracellular route. These findings suggest that NO donors may be useful to enhance the intestinal absorption of poorly absorbable drugs.

Animals↗
PubMed2001

Malignant eccrine spiradenoma: a case report and review of the literature.

BACKGROUND: Eccrine spiradenoma is a well-differentiated benign tumor of the sweat glands. Malignant change arising within eccrine spiradenoma is rare. OBJECTIVE: We describe a patient with malignant eccrine spiradenoma exhibiting both carcinomatous and sarcomatous differentiation. METHODS: Case report and literature review. RESULTS: A 37-year-old woman noted enlargement of a left axillary tumor that had been present for 20 years. The tumor was resected and the specimen, measuring 3.0 cm x 1.5 cm, revealed an encapsulated benign eccrine spiradenoma as well as an undifferentiated carcinoma possessing both carcinomatous and sarcomatous components. A transition zone was evident between the benign eccrine spiradenoma and the undifferentiated carcinoma, suggesting that the latter had arisen from the benign tumor. The malignant areas consisted principally of undifferentiated carcinoma (70%), although squamous cell carcinoma (10%), adenocarcinoma (10%), and chondrosarcomatous (10%) components were also present. Numerous mitotic figures were noted within the areas of malignant change, suggesting that the tumor was aggressive in nature. The patient died of systemic metastases 7 months after diagnosis. CONCLUSION: Although eccrine spiradenomas are usually benign, they can, on rare occasions, undergo malignant transformation. This case report describes one such occurrence of malignant transformation of a benign eccrine spiradenoma that unfortunately resulted in the patient's death from systemic metastases 7 months after diagnosis.

Adenoma, Sweat Gland↗
PubMed2001

Laparoscopic repair of colonic perforation associated with colonoscopy: use of passing sutures and endoscopic linear stapler.

Laparoscopic surgery recently has been conducted to repair colonic perforation that is associated with colonoscopy. The authors describe their laparoscopic repair of perforation using passing sutures and an endoscopic linear stapler. One 12-mm and several 5-mm trocars were inserted in the lower abdomen under general anesthesia. Observing with a laparoscope, passing sutures were threaded transversely through all layers of the margin of defect and pulled up with forceps to hold the margin straight, along which the defect was stapled with an endoscopic linear stapler. The authors applied this method for five patients, where the perforation occurred in the sigmoid colon or in the cecum (perforation size ranging from 10 mm to 50 mm). Perforation was successfully repaired in all patients, with no complications because of perforation or the procedures. The current method is beneficial because the perforated lesion is safely and easily closed and postoperative colonic stenosis is avoided.

Aged↗
PubMed2001

Analysis of Japanese encephalitis epidemic in Western Nepal in 1997.

We conducted an epidemiological study of a Japanese encephalitis (JE) outbreak in the southwestern part of Nepal in 1997. A high density of JE infections was found and it was estimated that 27.9% the total population were infected with JE virus in the study area. The fatality rate was 13.2% and there was no difference in the fatality rate between males and females over 5 years old. However, the case fatality rate was 2.1 times higher in females than in males (14.6% vs. 6.9%) among children under 5 years of age. Fifty-three blood samples were collected from suspected JE cases during the epidemic period in 1998. Findings for JE specific IgM revealed that clinical diagnoses of JE were serologically confirmed in an average 78% (70-93%) of patients in three collaborating hospitals. These studies demonstrated that JE was highly prevalent in the area and clinical diagnoses were reliable. Effective preventive measures should be taken against this vaccine-preventable disease.

Adolescent↗
PubMed2001

Novel compound heterozygous mutations for lipoprotein lipase deficiency. A G-to-T transversion at the first position of exon 5 causing G154V missense mutation and a 5' splice site mutation of intron 8.

We systematically investigated the molecular defects causing a primary LPL deficiency in a Japanese male infant (patient DI) with fasting hyperchylomicronemia (type I hyperlipoproteinemia) and in his parents. Patient DI had neither LPL activity nor immunoreactive LPL mass in the pre- and post-heparin plasma. The patient was a compound heterozygote for novel mutations consisting of a G-to-T transversion at the first nucleotide of exon 5 [+1 position of 3' acceptor splice site (3'-ass) of intron 4] and a T-to-C transition in the invariant GT at position +2 of the 5' donor splice site (5'-dss) of intron 8 (Int8/5'-dss/t(+2)c). The G-to-T transversion, although affecting the 11 nucleotide of the 3'-consensus acceptor splice site, resulted in a substitution of Gly(154) to Val (G154V; GG(716)C(-->)GTC). The mutant G154V LPL expressed in COS-1 cells was catalytically inactive and hardly released from the cells by heparin. The Int8/5'-dss/t(+2)c mutation inactivated the authentic 5' splice site of intron 8 and led to the utilization of a cryptic 5'-dss in exon 8 as an alternative splice site 133 basepairs upstream from the authentic splice site, thereby causing joining of a part of exon 8 to exon 9 with skipping of a 134-bp fragment of exon 8 and intron 8. These additional mutations in the consensus sequences of the 3' and 5' splice sites might be useful for better understanding the factors that are involved in splice site selection in vivo.

Adult↗