Photopenic area visualized on bone scintigraphy in a patient with eosinophilic granuloma.
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Child, Preschool↗
Biomedical subjects
I Yamamoto
Publications and source records attributed to I Yamamoto.
Marked uptake of TI-201 in intracranial extracerebral cavernous hemangioma.
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Aged↗
Effects of muscle relaxants on EEG, ABR and EMG in rabbits.
The effects of baclofen and pancuronium bromide on evoked electromyogram (EMG), cortical electroencephalogram (EEG) and auditory brainstem responses (ABR) were studied in pentobarbital anesthetized normal rabbits. Evoked EMG was measured in the gastrocnemius muscle by electrical stimulation of the sciatic nerve. Intravenous injection of baclofen decreased EEG and arterial blood pressure and light reflex, however, it had no significant influence on EMG or ABR at doses of 10 and 20 mg/kg/h. Pancuronium bromide immediately inhibited respiration, decreased EEG and EMG, however, it had no significant influence on arterial blood pressure, ABR, or light reflex, at doses of 0.4 and 1.0 mg/kg/h in anesthetized rabbits. ABR waves were observed until just before cardiac arrest with both of the muscle relaxants. It is suggested that ABR are not influenced by central or peripheral muscle relaxants, or by pentobarbital.
Acoustic Stimulation↗
Mitogen-activated protein kinase-dependent stimulation of proliferation of rat lactotrophs in culture by 3',5'-cyclic adenosine monophosphate.
Intracellular cAMP regulates cell proliferation as a second messenger of extracellular signals in a number of cell types. We investigated, by pharmacological means, whether an increase in intracellular cAMP levels changes proliferation rates of lactotrophs in primary culture, whether there are interactions between signal transduction pathways of cAMP and the growth factor insulin, and where the dopamine receptor agonist bromocriptine acts in the cAMP pathway to inhibit lactotroph proliferation. Rat anterior pituitary cells, cultured in serum-free medium, were treated with cAMP-increasing agents, followed by 5-bromo-2'-deoxyuridine (BrdU) to label proliferating pituitary cells. BrdU-labeling indices indicative of the proliferation rate of lactotrophs were determined by double immunofluorescence staining for PRL and BrdU. Treatment with forskolin (an adenylate cyclase activator) or (Bu)2cAMP (a membrane-permeable cAMP analog) increased BrdU-labeling indices of lactotrophs in a dose- and incubation time-dependent manner. The cAMP-increasing agents were also effective in increasing BrdU-labeling indices in populations enriched for lactotrophs by differential sedimentation. The stimulatory action of forskolin was observed, regardless of concentrations of insulin that were added in combination with forskolin. Inhibition of the action of endogenous cAMP by H89 or KT5720, a protein kinase A inhibitor, attenuated an increase in BrdU-labeling indices by insulin treatment. On the other hand, the specific mitogen-activated protein kinase inhibitor PD98059, which was effective in blocking the mitogenic action of insulin, markedly suppressed the forskolin-induced increase in BrdU-labeling indices. (Bu)2cAMP antagonized not only inhibition of BrdU labeling indices but also changes in cell shape induced by bromocriptine treatment, although forskolin did not have such an antagonizing effect. These results suggest that: 1) intracellular cAMP plays a stimulatory role in the regulation of lactotroph proliferation; 2) cAMP and insulin/mitogen-activated protein kinase signalings require each other for their mitogenic actions; and 3) the antimitogenic action of bromocriptine is, at least in part, caused by inhibition of cAMP production.
Animals↗
An increase in histone acetylation and IL-2 antagonizing the immunoinhibitory effect are necessary for augmentation by butyrate of in vitro anti-TNP antibody production.
We investigated the role of histone acetylation in the promotion of antigen-specific antibody production in murine B cells induced by sodium butyrate (NaBu) plus interleukin 2 (IL-2). NaBu dose dependently increased the acetylation levels of histone H4 at concentrations which effectively enhanced anti-trinitrophenyl (TNP) antibody production in the presence of IL-2. Among other short-chain fatty acids and NaBu analogs, propionate, valerate and vinylacetate were effective in the presence of IL-2 in increasing both antibody production and the histone H4 acetylation level, but acetate, alpha-, beta- and gamma-hydroxybutyrates and alpha-, beta- and gamma-aminobutyrates were not effective, even in the presence of IL-2. The effect of the specific histone deacetylase inhibitor trichostatin A (TSA), which enhances anti-TNP antibody production without IL-2, was markedly inhibited by adding NaBu simultaneously. However, the effect of TSA was neither inhibited nor potentiated by NaBu in the presence of IL-2. Splenic B cells treated with NaBu, TSA and both together in the presence or absence of IL-2 showed almost the same increased acetylation level of histone H4. These results suggest that the NaBu-induced enhancement of anti-TNP antibody production in the presence of IL-2 is mediated through a moderate increase in the level of histone acetylation and that NaBu has both stimulating and inhibiting activities for anti-TNP antibody production, the latter of which is overcome by IL-2.
Acetylation↗
Pharmacological effects in mice of anandamide and its related fatty acid ethanolamides, and enhancement of cataleptogenic effect of anandamide by phenylmethylsulfonyl fluoride.
Anandamide (N-arachidonoylethanolamine) and six fatty acid ethanolamides were synthesized and their pharmacological effects in mice were assessed using catalepsy, hypothermia and pentobarbital-induced sleep prolongation as indices. The effects of phenylmethylsulfonyl fluoride (PMSF) pretreatment on anandamide effects were also evaluated and discussed in relation to inhibition of anandamide amidohydrolase in mouse brain and liver. The cataleptogenic effect of anandamide (ED50=6.0 mg/kg, i.v.) was 4 to 6 times more active than those of N-oleoyl- (ED50=26.5 mg/kg, i.v.) and N-linoleoylethanolamine (ED50=37.5 mg/kg, i.v.), although the peak time in the effect was observed within 1 min after i.v. administration. None of the saturated fatty acid ethanolamides (N-myristoyl-, N-palmitoyl-, N-stearoyl- and N-arachidoylethanolamine) showed a positive response in the cataleptogenic effect even at a dose up to 40 mg/kg i.v. Anandamide, N-linoleoyl-, N-oleoyl- and N-myristoylethanolamine (10 mg/kg, i.v.) produced a significant hypothermia (0.19 to 0.59 degrees C) at 5 to 15 min after administration. The duration of the effects of these ethanolamides was also relatively short. Anandamide, N-linoleoyl-, N-oleoyl- and N-palmitoylethanolamine (5 or 10 mg/kg, i.v.) significantly prolonged pentobarbital-induced sleeping time by 148-207% of control sleeping time. The cataleptogenic effect of anandamide was markedly potentiated by pretreatment of mice with PMSF (100 mg/kg, i.p.). The ED50 (mg/kg, i.v.) of anandamide was 0.48 (0.24-0.96) in PMSF-pretreated mice. The pretreatment of mice with PMSF significantly decreased the metabolic clearance rate of anandamide in microsomal fractions of liver and brain. Thus, the Vmax/Km values of brain and hepatic microsomes were 26 and 10%, respectively, as compared with those of control mice. The present study demonstrated that anandamide and N-acylethanolamines of unsaturated fatty acids exhibited cannabinoid-like effects in mice, and that anandamide amidohydrolase has an important role in the pharmacological effects of anandamide in vivo.
Amides↗
Evaluation of induction of CYP3A mRNA using the HepG2 cell line and reverse transcription-PCR.
Cytochrome P-450 3A (CYP3A) is a drug-metabolizing enzyme dominant in the human liver. We have designed a useful method for evaluation of induction of CYP3A mRNA by various drugs using HepG2 cells known to retain liver-cellular functions. Using semi-quantitative reverse transcription-PCR (RT-PCR), we demonstrated that cultured HepG2 cells constitutively expressed CYP3A mRNA. This mRNA was expressed at high levels in culture for several days and was further induced by several drugs (e.g. rifampicin (RFP), dexamethasone). Treatment of HepG2 cells with RFP induced CYP3A mRNA in a dose- and time-dependent manner. Cells in culture for 48 h with 1 and 50 micromol/l RFP increased 2.7- and 5.0-fold in CYP3A mRNA expression in comparison with untreated controls, respectively. In contrast, no change in the amount of CYP3A mRNA was observed when the cells were treated with cimetidine which has been shown to inhibit CYP3A activity. Our method using a combination of HepG2 cells and RT-PCR allowed evaluation of the degree of induction of CYP3A mRNA both easily and rapidly.
Aryl Hydrocarbon Hydroxylases↗
Synthesis and pharmacological evaluation in mice of halogenated cannabidiol derivatives.
Six halogenated derivatives of cannabidiol (CBD, 1) substituted on the aromatic ring at the 3' and/or 5' position, 3'-chloro- (2), 3',5'-dichloro- (3), 3'-bromo- (4), 3',5'-dibromo- (5), 3'-iodo- (6) and 3',5'-diiodo-CBD (7) were synthesized and their pharmacological effects of barbiturate-induced sleep prolongation, anticonvulsant effects and locomotor activity were evaluated by intravenous (i.v.) injection in mice. 2 (10 mg/kg, i.v., 69 +/- 10 min) significantly prolonged pentobarbital-induced sleeping time by 3.1-fold, compared to control (22 +/- 2 min), although other 1 derivatives used did not significantly affect the sleeping time. 2, 4 and 6 (10 mg/kg, i.v.) significantly prolonged hexobarbital-induced sleeping time by 2.0-, 2.0- and 2.3-fold, respectively, compared with control (52 +/- 5 min). On the other hand, 1 and all halogenated derivatives did not significantly prolong barbital-induced sleeping time. The monohalogenated derivatives, 2, 4 and 6 were able to prolong pentobarbital and hexobarbital-induced sleeping time, although the dihalogenated derivatives, 3, 5 and 7 did not exhibit a prolongation of the sleeping time. All halogenated derivatives of 1 except for brominated derivatives (2, 3, 6, 7) tended to prolong tonic seizure latency induced by pentylenetetrazol. 1 and its halogenated derivatives did not exhibit any prolongation of seizure latency induced by picrotoxin or strychnine. Maximal electroshock test demonstrated that 1 and 4 exhibited almost the same potency in their anticonvulsant effects, although other 1 derivatives 2, 3, 5, 6 and 7 did not show significant effect up to a dose of 63 mg/kg, i.v. The ED50 values (mg/kg, i.v.) of 1 and 4 were 38 and 44, respectively. 1 and 4 also showed anticonvulsant effect in minimal and maximal electroshock-threshold tests. 2, 4 and 6 tended to decrease the total distance (horizontal activity) and number of rearings (vertical activity) of mice, whereas 3, 5 and 7 tended to increase the number of rearings. However, the effects of all derivatives were not statistically significant from the control. 2 and 4 were the most potent derivatives on pharmacological activities among the synthetic cannabinoids examined in the present study. These results indicate that monohalogenation of 1 leads to some modification of the pharmacological profile of CBD.
Animals↗
Synthesis and central nervous system depressant effects of N3-substituted 2',3'-O-isopropylideneuridines.
N3-Substituted derivatives of 2',3'-O-isopropylideneuridine (1) were synthesized and their pharmacological effects on the central nervous system (CNS) examined using mice. Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyls (8, 9, 10), and alpha-phenylethyl (11) derivatives of 1 were administered to mice by intracerebroventricular (i.c.v.) injection for evaluating hypnotic activity, pentobarbital-induced sleep prolongation, and spontaneous activity as indices. Only 3 possessed hypnotic activity by i.c.v. injection at the dose of 2.0 mumol/mouse. Compounds 3, 4, and 10 significantly showed synergism with a barbiturate, indicating that the derivatives have some CNS depressant effects. Moreover, 3 and 4 caused decrease in the spontaneous activity of mice, even at low doses. The present study indicated that substitution by ethyl, propyl, and p-xylyl groups at the N3-position of 2',3'-O-isopropylideneuridine imparted the CNS depressant effects.
Animals↗
[A DOPA antagonist, DOPA cyclohexyl ester inhibits transient brain ischemia-induced release of glutamate and delayed neuronal cell death in striatal and hippocampal region of in vivo rats].
We have previously obtained evidence that DOPA is probably involved in an upstream process of mechanisms for in vivo neuronal cell death in striatum. We attempted to clarify whether or not this is also the case in hippocampal region of conscious Wistar rats. Four vessels were occluded for 5 min during microdialysis of hippocampus. DOPA, dopamine and glutamate (Glu) in perfusates collected every 10 min were measured by HPLC-ECD and spectrophotometer. Delayed neuronal cell death in hippocampus was evaluated 96 hr after ischemia. Five-min transient brain ischemia induced Glu release, with the peak being 2.5-fold of a basal release at the fraction immediately after ischemia. The release of DOPA and dopamine was not consistently detectable, but an increase was sometimes observed during and after ischemia. Delayed neuronal cell death was slight to moderate with 5-min ischemia. Intrastriatal perfusion of DOPA cyclohexyl ester (DOPA CHE) at 100 nM, a novel stable potent competitive DOPA antagonist, almost completely inhibited the ischemia-induced glutamate release, and protected hippocampal neurons from delayed cell death. Endogenously released DOPA itself seems to act on its recognition site and to behave as a causal and/or deteriorating factor on glutamate release and resultant delayed neuronal cell death by transient ischemia in rats.
Animals↗
Involvement in denitrification of the napKEFDABC genes encoding the periplasmic nitrate reductase system in the denitrifying phototrophic bacterium Rhodobacter sphaeroides f. sp. denitrificans.
Seven genes, napKEFDABC, encoding the periplasmic nitrate reductase system were cloned from the denitrifying phototrophic bacterium Rhodobacter sphaeroides f. sp. denitrificans IL106. Two transmembrane proteins, NapK and NapE, an iron-sulfur protein NapF, a soluble protein NapD, a catalytic subunit of nitrate reductase precursor NapA, a soluble c-type diheme cytochrome precursor NapB, and a membrane-anchored c-type tetraheme cytochrome NapC were deduced as the gene products. Every mutant in which each nap gene was disrupted by omega-cassette insertion lost nitrate reductase activity as well as the ability of cells to grow with nitrate under anaerobic-dark conditions. A transconjugant of the napD-disrupted mutant with a plasmid bearing the napKEFDABC genes recovered both nitrate reductase activity and nitrate-dependent anaerobic-dark growth of cells. Denitrification activity, which was not observed in the napD mutant, was also restored by the conjugation. These results indicate that the periplasmic nitrate reductase encoded by the napKEFDABC genes is the enzyme responsible for denitrification in this phototroph, although the presence of a membrane-bound nitrate reductase has been reported in the same strain.
Cloning, Molecular↗
A novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification defect.
In this study we describe a novel mutation of the thyroid peroxidase (TPO) gene that resulted in a total iodide organification defect. TPO activity and thyroxine formation in thyroglobulin in the thyroid gland of the patient were below the limits of detection. However, TPO mRNA was detectable at a similar size and concentration as compared with normal thyroid tissues when measured by Northern blot analysis. Sequence analysis of the TPO gene showed the presence of two mutations, a missense mutation in exon 7 and C insertion in exon 14. These mutations were heterozygous and located in different alleles. The latter mutation has already been reported as one of the mutations of the TPO gene resulting in total iodide organification defect. The former mutation was further analysed by mRNA transfection studies in which mutated mRNA was transfected to CHO-K1 cells by electroporation. The results of transfection studies showed that the cells transfected with mutated mRNA expressed similar size TPO molecules to those of cells transfected with wild-type mRNA but that they lacked TPO activity. The two mutations of the TPO gene resulting in the total iodide organification defect in the patient cosegregated from her parents.
Adenoma↗
Dandy-Walker syndrome associated with occipital meningocele and spinal lipoma--case report.
A neonate presented with Dandy-Walker syndrome associated with occipital meningocele and spinal lipoma, manifesting as soft masses on the skull and lumbosacral regions. Magnetic resonance imaging demonstrated a large posterior fossa cyst between the fourth ventricle and occipital meningocele, but the aqueduct was patent and there was no sign of hydrocephalus. A cyst-peritoneal shunt was emplaced at the age of 8 days followed by partial removal of the spinal lipoma and untethering of the cord at the 3 months. Follow-up examination of age 3 years found almost normal development, although the cyst still persisted.
Adult↗
MR imaging of subchondral osteonecrosis of the vertebral body after percutaneous laser diskectomy.
OBJECTIVE: We describe four cases of subchondral osteonecrosis of the vertebral body that occurred after percutaneous laser diskectomy. Follow-up MR imaging after laser intervention showed abnormal findings in the vertebral body immediately adjacent to the site of diskectomy that are consistent with subchondral osteonecrosis. CONCLUSION: MR imaging features of this complication include a wedge-shaped low signal intensity on T1-weighted images, high and low signal intensities on T2-weighted images, and a contrast-enhanced area corresponding to high signal intensity on T2-weighted images. Possible causative mechanisms include thermal injury and photoacoustic shock.
Adolescent↗
[History of the treatment of Helicobacter pylori and clinical efficacy].
The combination of a proton pump inhibitor with antibiotics has been accepted as an effective treatment for the eradication of Helicobacter pylori and the most rational regimen to cure peptic ulcers. Triple therapies including two antibiotics and a proton pump inhibitor achieves constant and high eradication rate. The one-week, low-dose triple regimen including metronidazole has been accepted in European countries, but the new triple therapy with proton pump inhibitor, amoxicillin and clarithromycin is recommended for treatment of H. pylori infection in Japan. Quadruple therapy with two antibiotics, bismuth and a proton pump inhibitor is a second-line therapy. Triple therapy with ranitidine bismuth and two antibiotics may be promising.
Anti-Bacterial Agents↗
[Quantification of cerebral blood flow using 123I-IMP SPECT--a new method of estimating the input function from brain dynamic data].
In order to avoid continuous arterial blood sampling, we estimated input function by the method in that the whole brain time activity curves were fitted by two-term exponential function and differentiated analytically after the injection of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). This method was applied to 4 patients with cerebral infarction and 2 patients with brain tumor. Values of regional cerebral blood flow (rCBF) were calculated from the input function calibrated by one-point arterial sampling at 5 minutes after the injection using microsphere method, and then were compared with those obtained from the table-lookup method. In this study, we used the individual input function for the table-lookup method instead of the standard input function. The overall accuracy errors between two-term exponential functions and the whole brain time-activity curves were about 1%. The values of rCBF calculated by this method were well correlated with those by the table-lookup method (r = 0.901, p < 0.001). Optimal calibration time for this method was between 3-minute and 10-minute after 123I-IMP injection and the deviation of the rCBF values obtained by this method from those obtained by the table-lookup method in which the input function was calibrated at 5 minutes remained within 10%. This method is a less invasive and convenient alternative to the conventional methods which require continuous arterial blood sampling.
Adult↗
Increased resistance of the radiosensitive M10 mutant cells of the L5178Y mouse lymphoma cell line to heat-induced apoptosis.
M10 cells, which are deficient in the repair of DNA DSBs and are therefore radiosensitive, are about twofold more thermoresistant than their parental L5178Y cells. We found that, after heat shock at 43 degrees C under conditions resulting in 10% survival (D(10)), M10 cells did not undergo apoptosis, whereas L5178Y cells did undergo apoptosis. M10 cells, but not L5178Y cells, constitutively expressed Hsp72 protein. Moreover, the M10 cells accumulated higher amounts of the heat-inducible form of Hsp72. The patterns of activation of the DNA-binding activity of HSF (heat-shock factor) differed in M10 and L5178Y cells. In response to heat shock, M10 cells accumulated greater amounts of Trp53 protein (formerly known as p53) than the parental cells. Cdkn1a (formerly known as p21, Waf1) was constitutively expressed and further accumulated after heat shock only in M10 cells. We suggest that heat-inducible Hsp72 to a larger extent, and constitutive Hsp72 to a lesser extent, together with Cdkn1a may be involved in the protection of M10 cells against heat-induced apoptosis. Apoptosis in these cells is likely to occur in Trp53-dependent manner.
Animals↗