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Biomedical subjects

I Yamamoto

Publications and source records attributed to I Yamamoto.

At least 163 records · Page 9Linked to original sources

Distribution and characterization of anandamide amidohydrolase in mouse brain and liver.

Anandamide (N-Arachidonoylethanolamine) amidohydrolase catalyzing hydrolysis of anandamide was characterized in mice. The enzymatic activity was highest in the liver, followed by the brain and testis. Negligible activity was found in heart, lung and spleen. The activity in brain and liver was mainly localized in the microsomal fractions. Kinetic experiments demonstrated that Km (microM) and Vmax (nmol/min/mg protein) for the brain microsomes were 9.3 and 2.58, respectively, while those for the hepatic microsomes were 180 and 18.9, respectively. The activity in the microsomes from the liver and brain was markedly inhibited by Cu2+, Hg2+, Se4+, phenylmethylsulfonylfluoride and sodium dodecylsulfate. Brain but not hepatic microsomal enzyme activity was inhibited by delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Kinetic parameters demonstrated that the inhibition by the cannabinoids was competitive in nature. Relatively high distribution of the enzyme activity in brain suggests an importance of the enzyme in the central nervous system to regulate the neuromodulatory fatty-acid amides.

Amidohydrolases↗

The pharmacokinetic change of lidocaine by catecholamines using isolated perfused rat liver (IPRL).

We hypothesized that changes in the pharmacokinetics of lidocaine might reveal changes in portal circulation induced by catecholamines. Isolated perfused rat liver (IPRL) was selected as an experimental model, since experimental conditions in this model could be regulated. The liver was perfused with a recirculating system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was administered along with one of three drugs, dopamine, norepinephrine or adenosine triphosphate. The fractional transfer rate constants, k21 and k12, from medium to liver and liver to medium, respectively, and ke, the elimination rate constant, were calculated using a two-compartment model with the SAAM II program. Curves of decay of lidocaine from the recirculating medium consisted of a fast and a slow component. Norepinephrine and high-dose dopamine significantly increased k12, while low-dose dopamine significantly increased k21 and ke compared with control values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer rate from liver to medium, while low-dose dopamine increased the transfer rate from medium to liver and the rate of elimination from liver. These findings suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake and that low-dose dopamine improves uptake in IPRL.

Anesthetics, Local↗

Intradural extension of mucocele complicating frontoethmoid sinus osteoma: case report.

BACKGROUND: Osteomas of the paranasal sinus are often asymptomatic and are sometimes complicated by mucoceles, but intradural extension of such a mucocele has rarely been reported. CASE DESCRIPTION: This 67-year-old man with complaint of headache was diagnosed as having an intradural extension of a mucocele complicating an osteoma of the frontoethmoid sinus. A right frontobasal craniotomy was performed and a mucocele in the frontal sinus extending into the frontal lobe through two dural defects and the osteoma was removed completely. The patient was successfully treated without recurrence. CONCLUSION: The importance of radical surgery for such lesions and the relationship between osteomas and mucoceles are discussed.

Aged↗

SKW 6.4 cell differentiation induced by interleukin 6 is stimulated by butyrate.

We investigated if sodium butyrate (NaBu), an inhibitor of histone deacetylase, and its analogs modulate cytokine-induced differentiation of the human B cell line SKW 6.4 transformed by the Epstein-Barr virus. NaBu markedly enhanced interleukin (IL)-6-induced IgM production with an accompanying increase in the level of histone H4 acetylation and augmented IgM production induced by IL-4 and phorbol 12-myristate 13-acetate. From both the enhancing effect of cell differentiation and the effect of inducing histone hyperacetylation in SKW 6.4 cells, other histone deacetylase inhibitors and NaBu analogs were divided into three groups: those that increased both IL-6-induced antibody production and histone acetylation, those that caused histone hyperacetylation, but failed to induce the differentiation, and those that were ineffective at inducing either activity. No agent that enhanced IgM production without inducing histone hyperacetylation was found among the inhibitors and analogs we tested. These results suggest that the increase in the histone acetylation is necessary, but it is insufficient to augment differentiation of SKW 6.4 cells. Thus another activity of NaBu in addition to the inhibition of histone deacetylase may be involved in promoting IL-6-induced differentiation. Our results also suggest that fatty acids that have a straight chain of four carbon atoms or are branched with four and five carbon atoms, which contain no hydrophilic substituents, or those with similar structures, show this other activity.

Acetylation↗

Stimulation of hepatocyte growth factor production by ascorbic acid and its stable 2-glucoside.

Hepatocyte growth factor (HGF), a cytokine which is generally produced by mesenchymal cells, has mitogenic, motogenic and morphogenic activities in epithelial cells and it also has tumor-suppressing activities. Induction of HGF production may be involved in organ regeneration, wound healing and embryogenesis. We examined the effects of ascorbic acid (AsA), which stimulates the proliferation of fibroblasts, and its stable derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), on HGF production by human skin fibroblasts. Basal HGF secretion was significantly stimulated by more than 0.1 mM AsA or AA-2G. Both vitamins synergistically enhanced HGF secretion stimulated by growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), cholera toxin and other inducers. Induction by EGF or bFGF was most markedly potentiated by the vitamins. HGF production by the KG-1 human leukemia cell line was also augmented by AsA or AA-2G. Another stable AsA derivative, ascorbic acid 2-phosphate (AA-2P) effectively promoted basal and EGF-induced HGF secretion by the fibroblasts, but ascorbic acid 2-sulfate (AA-2S) was much less effective. Intracellular AsA levels increased after the addition of AA-2G and AA-2P as well as AsA, but not after AA-2S. The effect of AA-2G was completely abrogated by the simultaneous addition of castanospermine, an alpha-glucosidase inhibitor, suggesting that the active form of AA-2G is AsA. Constitutive and EGF-induced HGF gene expression was also up-regulated after adding AsA or AA-2G to the cells. These results indicated that AsA acts alone or in synergy with several inducers to stimulate the production and gene expression of HGF in human skin fibroblasts and that the stable AsA derivative AA-2G is as effective as AsA in promoting HGF production.

Acetylcysteine↗

Bone fragility induced by X-ray irradiation in relation to cortical bone-mineral content.

PURPOSE: A large single dose of irradiation to bone tissue causes bone fragility, and such bone will be susceptible to fracture even without trauma. The purpose of this study was to investigate the effects of fractional irradiation on the biomechanical properties of bone in the rat in relation to the cortical bone-mineral content (BMC), and to compare these effects with those brought about by single-dose irradiation. MATERIAL AND METHODS: Seventy-five veteran female Wistar rats were divided into 4 groups. Group 1 was the control group. The left tibiae of the remaining rats were exposed to irradiation. Group 2 received one single dose of X-rays at 10-60 Gy. Groups 3 and 4 received fractional irradiation up to different cumulative doses (10-60 Gy): group 3 received 2.5 Gy once a day; group 4 received 1.25 Gy twice a day. Twenty-four weeks after irradiation, the rats were killed and the BMC in each tibial diaphysis was determined by dual-energy X-ray absorptiometry (DXA). The bones were then loaded to failure in a three-point bending test. RESULTS: The control group showed no difference (p>0.05) between left and right tibiae, neither in BMC nor in the maximum load at fracture. Single-dose irradiation caused a 16% (p=0.0366) decrease in the maximum load at 40 Gy, and a 19% (p=0.008) decrease at 60 Gy. The once-daily fractional dose of irradiation caused a 10% (p=0.0022) decrease in the maximum load of the irradiated tibiae at 60 Gy when compared to the intact contralateral tibiae. The twice-daily fractional dose of irradiation had no observable effect on the maximum load of the irradiated tibiae. Neither fractional irradiation modality had an effect on BMC. CONCLUSION: The study suggested that bone fragility induced by single fractional irradiation doses (given once daily up to high cumulative doses) was not associated with change in the cortical BMC. It also confirmed the preference for twice-daily fractional irradiation as compared to once-daily fractional irradiation and the total single dose.

Absorptiometry, Photon↗

Relevance of a new impedance matching, or subtrap, method for the reduction of pain during hyperthermia.

Capacitive heating is widely used in hyperthermic treatment of human malignancies. However, the pain on the body surface or thermoesthesia in the subcutaneous fatty layer may prevent an elevation of temperature in the tumors. Impedance matching is improved by a subtrap method entailing the application of two copper plates (10 x 850 x 0.06 mm) as a subtrap circuit to each of two capacitive electrodes. In a clinical trial the Tmax, Tave, Tmin for the subtrap method were all higher in comparison with those for the conventional technique (42.5 +/- 0.7 degrees C, 41.9 +/- 1.0 degrees C, 41.3 +/- 1.1 degrees C vs. 41.1 +/- 1.5 degrees C, 40.6 +/- 1.3 degrees C, 40.0 +/- 1.3 degrees C). Although the maximal radiofrequency (RF) power applied to patients was higher with the subtrap method (875 +/- 189 W vs. 763 +/- 200 W), the incidence of surface pain was reduced dramatically. It is concluded that the subtrap method substantially improves the RF capacitive heating of deep-seated tumors.

Adolescent↗

Gene and cDNA structures of flounder insulin-like growth factor-I (IGF-I): multiple mRNA species encode a single short mature IGF-I.

To understand the comprehensive mechanisms of gene expression and processing for insulin-like growth factor-I (IGF-I) in vertebrates, we have investigated the gene organization, promoter and transcriptional initiation sites, alternative splicing and polyadenylating sites, and the cDNA structures of this gene in the Japanese flounder, Paralichthys olivaceus. The flounder IGF-I gene was found to be composed of five exons and four introns spanning 17.5 kb. By Northern blot analysis, two major mRNA classes of 4.7 kb and 2.9 kb were found in the liver. cDNA cloning and reverse transcription polymerase chain reaction (RT-PCR) analysis indicated that these two mRNA classes result from two different-sized 3'-noncoding regions generated by alternative usage of two polyadenylating signals. Further analysis by RT-PCR and sequencing revealed that these mRNA classes both contain two subclasses of mRNA encoding two forms of IGF-I prepropeptide, preproIGF-I-1 and preproIGF-I-2. The two forms of preproIGF-I share the identical signal peptide and mature IGF-I domain but contain different E domains as a result of alternative splicing in exon 3. The mature form of flounder IGF-I was found to comprise 68 amino acid residues, showing a small molecular weight, 7486. In the 5'-flanking region, one major and four minor transcription start sites have been identified by ribonuclease protection assay between -230 and -130 from the translation initiation codon, but no canonical TATA box or GC box was detected in their upstream regions up to -724. The results suggest that some unknown transcription initiation factors are functioning in the promotion of IGF-I gene expression.

Amino Acid Sequence↗

Characterization of a cDNA encoding CuZn-superoxide dismutase from the liverwort Marchantia paleacea var. diptera.

Suspension-cultured cells of the liverwort Marchantia paleacea var. diptera contain a cytosolic CuZn-superoxide dismutase (SOD) whose N-terminal amino acid sequence is similar to those of the isozymes found in chloroplasts of higher plants [Tanaka et al. (1996) Plant Cell Physiol. 37: 523]. A cDNA (MSODCc) encoding the cytosolic CuZn-SOD was isolated from cDNA library constructed from a liverwort cell suspension culture. The deduced amino acid sequence showed a higher degree of homology with the sequences of CuZn-SODs in chloroplasts than those in the cytosol of higher plants and an unique additional peptide in the C-terminal region, but no plastid transit sequence. Northern blotting using MSODCc as a probe and immunoblot analysis with antiserum against the enzyme revealed that the steady state level of transcript was not affected by copper, but both CuZn-SOD protein and its activity increased.

Amino Acid Sequence↗

Improvement of age estimation using amino acid racemization in a case of pink teeth.

Age was estimated from pink teeth using racemization of dentinal aspartic acid. Materials for identification were two lower second premolars. The body was determined to be that of a 40-year-old man; however, the age of the decedent had been estimated to be 29 and 30 years by the conventional method and 30 years from findings in the oral cavity. To clarify the cause of this difference, the powdered teeth were further washed in 0.01 mol/L hydrochloric acid. The racemization ratio (D/L ratio) of ordinary white teeth from persons of known age was slightly lower than that before washing, whereas that of the teeth used for identification was higher than before washing. The calculated age of the decedent using the racemization ratio of his teeth was between 36 and 37 years. These results suggest that age estimated from pink teeth is probably underestimated, but a more accurate age estimate can be obtained after adequate washing.

Adult↗

Evaluation of oral mucoadhesive microspheres in man on the basis of the pharmacokinetics of furosemide and riboflavin, compounds with limited gastrointestinal absorption sites.

When sustained-release adhesive and non-adhesive microspheres which release the same drugs at similar rates are administered orally, drug absorption after administration of adhesive microspheres should, if the gastrointestinal residence of adhesive microspheres is prolonged as a result of mucoadhesion, be higher than that after administration of non-adhesive microspheres. The gastrointestinal transit of oral adhesive microspheres in man has been evaluated pharmacokinetically using furosemide and riboflavin, compounds with limited absorption sites in the upper small intestine. In a preliminary experiment with fasted rats it was confirmed that a higher percentage of the drug remained in the stomach and that plasma drug levels were higher when furosemide was administered in the form of adhesive rather than non-adhesive microspheres. Two kinds of sustained-release microsphere, adhesive and non-adhesive, containing furosemide and riboflavin in hard gelatin capsules were prepared and orally administered to 10 healthy fasted volunteers in a cross-over design. Areas under the plasma concentration-time curves (AUC) were 1.8 times larger for furosemide and urinary recovery was 2.4 times higher for riboflavin when adhesive microspheres rather than when non-adhesive microspheres were used. When adhesive microspheres containing riboflavin were administered to fed volunteers, urinary recovery was 2.1 times higher and mean residence time (MRT) was more prolonged than when the microspheres were administered to fasted volunteers. Adhesive microspheres were found to adhere to the gastric or intestinal mucosa with high affinity in man and rats, resulting in prolonged gastrointestinal residence.

Adhesives↗

Isolation of a periplasmic molecular chaperone-like protein of Rhodobacter sphaeroides f. sp. denitrificans that is homologous to the dipeptide transport protein DppA of Escherichia coli.

A periplasmic protein has been found to prevent aggregation of the acid-unfolded dimethyl sulfoxide reductase (DMSOR), the periplasmic terminal reductase of dimethyl sulfoxide respiration in the phototroph Rhodobacter sphaeroides f. sp. denitrificans, in a manner similar to that of the Escherichia coli chaperonin GroEL (Matsuzaki et al., Plant Cell Physiol. 37:333-339, 1996). The protein was isolated from the periplasm of the phototroph. It had a molecular mass of 58 kDa and had no subunits. The sequence of 14 amino-terminal residues of the protein was completely identical to that of the periplasmic dipeptide transport protein (DppA) of E. coli. The 58-kDa protein prevented aggregation to a degree comparable to that of GroEL on the basis of monomer protein. The 58-kDa protein also decreased aggregation of guanidine hydrochloride-denatured rhodanese, a mitochondrial matrix protein, during its refolding upon dilution. The 58-kDa protein is a kind of molecular chaperone and could be involved in maintaining unfolded DMSOR, after secretion of the latter into the periplasm, in a competent form for its correct folding.

Amino Acid Sequence↗

Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor.

Interactions of anandamide (N-arachidonylethanolamide), an endogenous compound for cannabinoid receptors, with the receptors for 5-hydroxytryptamine (5-HT), benzodiazepine, and gamma-aminobutyric acid(A) (GABA[A]) receptors in bovine synaptic membrane were examined. Anandamide decreased the 5-HT receptor bindings at concentrations of 1-100 microM, although it did not cause any change in benzodiazepine or GABA(A) receptor bindings. A high concentration of anandamide, 100 microM, significantly decrease both [3H]5-HT and [3H]ketanserin bindings. The present study revealed that the pharmacological activity of anandamide might be partially mediated through the 5-HT receptor.

Animals↗

Competitive inhibition of delta8-tetrahydrocannabinol and its active metabolites for cannabinoid receptor binding.

In vitro binding characteristics of delta8-tetrahydrocannabinol (delta8-THC) and its metabolites, 11-hydroxy-delta8-THC (11-OH-delta8-THC) and 11-oxo-delta8-THC, as well as an inactive metabolite, delta8-THC-11-oic acid, as a cannabinoid receptor site from bovine cortex were examined using the specific agonist [3H]CP-55940. 11-OH-delta8-THC and 11-oxo-delta8-THC strongly inhibited the specific binding of [3H]CP-55940. The Ki values of 11-OH-delta8-THC and 11-oxo-delta8-THC for the specific binding of [3H]CP-55940 were 52 and 143 nM, respectively, whereas that of delta8-THC-11-oic acid was 917 nM. Scatchard plot analyses indicated that 11-OH-delta8-THC and 11-oxo-delta8-THC caused a significant increase in the apparent KD value without changing the apparent Bmax. These results reveal that active metabolites of delta8-THC also competitively bind to the cannabinoid receptor as agonists.

Animals↗

Enhancing effect of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid, a stable ascorbic acid derivative, on collagen synthesis.

The objective of the present study was to compare 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) with ascorbic acid (AA) and ascorbic acid 2-phosphate (AA-2P) concerning the promotion of collagen production in human skin fibroblasts. Though AA-2G was still observed to be promoting collagen synthesis at the same level on the 8th day of the culture, collagen synthesis was seen to decrease on the fifth day of culturing with AA and AA-2P. This sustained collagen synthesis-promoting action is considered to be a major feature of the novel vitamin C derivative, AA-2G by conducting an experiment in which an alpha-glucosidase inhibitor was present, it was shown that AA-2G exerts its collagen synthesis-promoting action after being decomposed to AA by alpha-glucosidase. Further, we observed that for AA-2G, even on the 8th day of the culture, the amount of AA in the fibroblasts was virtually unchanged from the beginning of the experiment, whereas, in the case of adding AA and AA-2P, virtually no AA was detectable in the culture medium on the fifth day. These findings suggests that AA-2G is decomposed to AA by alpha-glucosidase in the cells. This AA promotes collagen synthesis, which is prolonged through AA-2G's sustained decomposition.

Ascorbic Acid↗

Synthesis and sedative-hypnotic effects of N3-allyl- and N1-allyl-5,6-substituted 2-thiouracil derivatives in mice.

Twenty four thiouracil derivatives, including N3-allyl- (19) and N1-allyl-2-thiouracil (20) were synthesized and their pharmacological effects [sedative-hypnotic activity (loss of righting reflex and spontaneous activity), convulsant activity, effect on pentobarbital (PB)-induced sleep and mortality] were evaluated in mice at doses of 320 mg/kg, i.p. and 2 mumol/mouse by intracerebroventricular (i.c.v.) injections, respectively. N3-Allyl-6-propyl-2-thiouracil (3), N3-allyl-5,6-dimethyl-2-thiouracil (10), N3-allyl-1,2,3,4,5,6,7,8,9-nonahydro-4-oxo-2-thiocyclohepta [d]pyrimidine (16) and N3-allyl-5-methyl-2-thiouracil (18) exhibited sedative-hypnotic activity, whereas N3-allyl-6-ethyl-5-methyl-2-thiouracil (11), N1-allyl-5-methyl-2-thiouracil (21), N1-allyl-1,2,3,4,5,6,7,8,9-nonahydro-4-oxo-2-thiocyclohepta[ d]pyrimidine (23) and N1-allyl-5,6-dimethyl-2-thiouracil (24) conversely displayed clonic- and/or tonic-convulsant seizures. N3-Allyl-6-propyl-2-thiouracil (3) and N3-allyl-5-methyl-2-thiouracil (18) decreased spontaneous activity. Other compounds examined were inactive, or only slightly active in the sedative-hypnotic assay even at high doses. Fifteen compounds (1-4, 7, 10, 11, 14-16, 18-21, and 23) significantly prolonged the PB-induced sleeping time. Interestingly, only N1-allyl-5,6-dimethyl-2-thiouracil (24) shortened the PB-induced sleeping time. These results showed that these thiouracils possessed many different effects such as sedative-hypnotic, anticonvulsant and/or convulsant, and that N3-allyl-5-methyl-2-thiouracil (18) and N1-allyl-5,6-dimethyl-2-thiouracil (24) had the most potent hypnotic activity and antagonistic effect against PB, respectively.

Animals↗