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This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19)genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Results of coherent edge fluctuation measurements using three diagnostics (a reciprocating Langmuir probe, a two channel O-mode reflectometer, and fast magnetic probes) in H-mode discharges on JFT-2M are presented. In discharges in which a high recycling steady (HRS) H-mode phase is obtained through a transient phase with slightly enhanced D_α intensity, two types of coherent fluctuations are observed. The higher frequency mode (around 300 kHz) is the high frequency mode (HFM) observed in the HRS H-mode (Kamiya K et al 2003 9th IAEA Tech. Meeting H-mode Workshop Topic B-14). The lower frequency mode has a frequency of around 80 kHz. The HFM is detected by a Langmuir probe over a wide region in the SOL, as well as by the reflectometer and magnetic probes. However, the HFM is not detected by the higher frequency (38 GHz) channel of the reflectometer after the HRS transition, suggesting that the HFM is not located deeply inside the plasma. The 80 kHz mode is detected by both channels of the reflectometer and by a Langmuir probe, but not by magnetic probes, suggesting that it is an electrostatic mode. In contrast to the HFM, the 80 kHz mode is detected by the Langmuir probe only near the separatrix during the transient phase, which leads to either the HRS phase or the ELMy phase, and is similar to the fluctuations reported in Shinohara K et al (1998 J. Plasma Fusion Res. 74 607).

The Large Area Air Shower (LAAS) group has been performing a network observation of extensive air showers (EAS) since 1996 in Japan. Eight compact EAS arrays (ten in the near future) are operating simultaneously and independently at distant stations (up to ≈ 1000 km), constituting a gigantic detector system as a whole. Using five stations' datasets, large-scale coincidences of EAS have been searched for with the aim of detecting signals from extremely short bursts in the universe. By comparing arrival times and arrival directions of all registered EAS, three coincident and parallel EAS pairs were extracted out of a sea of background cosmic rays. One of them was observed almost from the direction of the Crab Nebula, a previously reported ultra-high-energy γ-ray source. The first application reported here allows the analysis techniques to be tested and demonstrates the potential of observations with the full operation of the network detector system.

To investigate structure–activity relations between the sugar chain structures of triterpenoid saponins and their plant growth regulation effects, several monodesmosidic saponins with betulin as an aglycon were synthesized by chemical and enzymic reactions. Three triterpenoids (betulin, betulinic acid, oleanolic acid) and synthesized betulin glycosides were submitted to germination and growth regulation tests on alfalfa seeds. We concluded the following. Betulin had a slight growth inhibitory effect on alfalfa radicles. Betulin glycosides exhibited stronger effects than betulin, and betulin glycosides with two to four glucose residues as a sugar moiety had the greatest inhibitory activity. These characteristics of growth inhibitory effects were considerably different from those of phenolic compounds so far reported. Some betulin glycosides also showed a significant growth regulation effect on alfalfa hypocotyls. However, hypocotyl growth was less affected than radicle growth for all betulin glycosides. Among the triterpenoids, betulinic acid had stronger growth inhibitory effects on alfalfa radicles than betulin, suggesting the importance of the carboxyl group at the C-28 position for the inhibitory effects of lupane-type triterpenoids. On the other hand, no germination regulation effects on alfalfa seeds were observed for any of the betulin glycosides or triterpenoids examined.

SummaryFour flavonoid compounds, ((+)-taxifolin, (+)-aromadendrin, quercetin and (−)-naringenin), from Japanese larch (Larix leptolepis) wood were heated at 170 ℃C for 60 min at pH=3.46 (hydrothermolysis treatment). Alphitonin, four taxifolin steric isomers and quercetin were recovered from the treatment of (+)-taxifolin, and maesopsin, four aromadendrin steric isomers and kaempferol from (+)-aromadendrin. The reaction products from (−)-naringenin were found to be a mixture with (+)-naringenin. Quercetin was not changed by the treatment. Possible pathways for the formation of these products are discussed.

We report on an autopsy findings of a 92‐year‐old male with hemiballism‐hemichorea associated with hyperglycemia and striatal hyperintensity on T1‐weighed magnetic resonance imaging (MRI), a recently described clinicoradiological syndrome. Histologically, the putamen contralateral to the hemiballism consisted of multiple foci of recent infarcts associated with reactive astrocytic and interneuronal response. Substrate responsible for the MRI signal changes is still inconclusive. © Movement Disorder Society.

SummaryThis paper deals with the results of choice feeding tests of two termite species, Coptotermes formosanusShiraki and Reticulitermes speratus(Kolbe), with steam-treated and dry-heated samples of Japanese commercial woods. Some steam-treated species were heavily attacked by C. formosanusand R. speratuswhile all dry-heated samples were attacked not more than unheated controls except for the combination Japanese larch-R. speratus. The steam treatment in some wood species produced feeding attractants which were removed by hot water extraction. Termite species showed some differences in the susceptibility to these substances. Attraction of the termites to steam-treated Japanese beech was different from that to the steam-treated softwoods. These phenomena were discussed with references to heat treatment of wood as well as to termite attractive factors.

Abstract: We report on the autopsy of a 52-year-old Down’s syndrome patient with a 9-year history of progressive dementia. Histologically, there was a marked neuronal loss in the cerebral cortices with numerous neurofibrillary tangles and senile plaques and congophilic angiopathy. The second cortical layer was spongy in appearance and the frontal and temporal white matter showed marked myelin pallor. Immunohistochemistry for MAP2 of the frontal and temporal cortices revealed great reduction in the number of large pyramidal neurons. On the other hand, a much stronger MAP2 immunoreactivity than that seen in the controls was observed in the second layer, which consisted of many small pyramidal neurons with features of aberrant sprouting. They were recognized in the frontal cortices but not in the temporal cortices, and were not immunolabeled with phosphorylated-tau nor MAP5. On double immunolabeling with MAP2 and β-amyloid antibodies, these neurons were found to be not directly associated with the formation of senile plaques. Ultrastructurally, MAP2 was immunolocalized in an amorphous granular form in the neuronal somata and processes, and paired helical filaments were not immunolabeled. The observation may indicate the occurrence of a remarkable plastic response of small pyramidal cortical neurons in this patient with Down’s syndrome.

Abstract: We report an autopsy case of a 64 year-old Japanese man diagnosed as having leukoencephalopathy caused by tegafur, a 5-fluorouracil derivative, and review seven previous cases, mostly reported in Japan. In the present case, tegafur had been orally administered for the shortest period of 3 weeks in pre- and postoperative cancer chemotherapy. He died 2 years later after having made a slight recovery from a prolonged akinetic mute state. Unlike similar cases previously reported, the degeneration of the white matter was most prominent in the temporal lobes. Histologically, the severely involved white matter showed nearly complete myelin and axonal loss with a proliferation of hypertrophic astrocytes. In the less severely involved areas, such as in the frontal white matter where myelin was relatively well preserved, numerous activated microglial cells and a small number of T lymphocytes were identified immunohistochemically. The cerebral cortex, cerebellum and brain stem were well preserved, which is consistent with the previous reports. Literature review revealed that the histopathological features of the lesions reported in human cases are quite different from those reported in animal experiments.

A comparison was made of the effects of a nonsulfhydryl compound, vitamin U (methylme-thioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine (Cys), with regard to the inducement of acute gastric mucosal damage in the presence and absence ofN-ethylmaleimide (NEM), a sulfhydryl-blocking reagent. The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to 50% ethanol. The preinjection of NEM had no effect on cytoprotection of prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased surface mucin content but lessened that of deep mucin. NEM decreased surface mucin and increased deep mucin. It thus follows that sulfhydryl compounds accelerate the secretion of deep mucin and accumulate surface mucin. The cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds, and the increase in surface mucosal mucin may possibly be related to cytoprotection.

A case of esthesioneuroepithelioma was investigated ultrastructurally and immunohistochemically, using antibodies against neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), keratin, neuron-specific enolase (NSE), S-100 protein (S-100), and tyrosine hydroxylase (TH). The tumor initially manifested as an epidural mass in the anterior cranial fossa in a 64-year-old man, and about 31/2 years later, autopsy further revealed extensive metastases to the lymph nodes of the neck and thoracic cavity. In the cranial and nasal cavities, the tumor was composed of fairly uniform, ill-defined cells arranged in nests which were surrounded by a fibrovascular stroma. These histological features were reproduced in the metastatic tumor nodules with frequent occurrence of tubular arrangements of the tumor cells. Ultrastructurally, two different cell types were well recognized by their characteristic morphological features, which were reminiscent of sensory neurons and sustentacular cells of the olfactory epithelium. No dense-cored secretory granules were observed in the tumor cells. Immunohistochemically, the tumor showed a variable number of cells positive for NFP, keratin, NSE and S-100. NFP was present in a relatively small number of cells, which were found diffusely in the nests. Keratin was observed in the cells mainly located at the periphery. NSE-positive cells tended to form irregular clusters in the center. A few S-100-positive cells were found, without any particular arrangement. These findings indicated that the present tumor, which actually arose in the superior nasal cavity, consisted of cells differentiating in at least two distinct directions, neuronal and epithelial, and strongly suggested that the tumor was of true olfactory epithelium origin, or more precisely, derived from the bipotential, undifferentiated basal cells of this epithelium.

We studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 µm in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Ultrastructural studies were made on the distal segments of the mouse phrenic nerve after crush injury. In the control, endoneurium contained only unfenestrated capillaries. In the experiment, from day 2 to day 6, endoneurial capillaries occasionally showed fenestrations with the attenuation of its cytoplasm. At this stage, axonal degeneration and myelin breakdown became evident showing early stage of Wallerian degeneration. In addition, detachment of the neighboring endothelial cells concomitant with the invasion of macrophage was also observed. These findings were previously unobserved changes of the endoneurial endothelium in Wallerian degeneration. The significance of the early occurrence of fenestrae was discussed briefly.

To examine effects of bestatin on the host immunity of patients with urogenital cancer, 54 patients were randomized into 2 groups: bestatin treated and controls. In each group, the patients were divided into 2 subgroups: one which received basic treatment expected to greatly affect host immunity (‘invasive treatment’) while the other one received other types of basic treatment (‘non-invasive treatment’). Peripheral lymphocyte, OKT 4/8 ratio and purified protein derivative (PPD) skin reaction were used as immunological markers. There were significant differences in the ‘invasive’ treatment group between bestatin treated patients and controls concerning lymphocyte counts and PPD skin reactions and in the ‘non-invasive’ group concerning lymphocyte counts and OKT 4/8 ratios. These results suggest that bestatin may potentiate host immunity in patients with urogenital cancer. Further studies on larger materials are, however, needed before more definite conclusions can be drawn.

Mucins, high-M(r) glycoproteins with a large amount of O-glycosidically linked carbohydrate, protect the colonic epithelial surface and are altered in ulcerative colitis and colon cancer. At least two mucin genes, MUC2 and MUC3, are expressed at high levels in the human intestine. As an experimental model for studying the biosynthesis of human intestinal mucins, we used HM3 colon cancer cells. When mature mucins labelled with [3H]glucosamine or [3H]threonine were analysed by gel filtration, it was found that secreted mucins (M(r) > 10(8) were larger than soluble cellular mucins (M(r) approx. 5 x 10(6)). Only secreted mucin was sensitive to reduction. Both MUC2 and MUC3 proteins, identified by labelling with [3H]threonine or [35S]cysteine and immunoprecipitation with antibodies to synthetic mucin peptides, were already of large size (M(r) > 180,000) by the earliest labelling time (5 min). The MUC3 precursor was completely degraded by trypsin, but the MUC2 precursor had a trypsin-resistant fragment of M(r) approx. 240,000 containing threonine and cysteine. The trypsin-resistant MUC2 fragment contained N-linked carbohydrate, as indicated by a decrease in size as a result of peptidyl N-glycosidase digestion or tunicamycin treatment of HM3 cells. These results show that HM3 colon cancer cells produce at least two distinct human intestinal mucins. They also indicate that the mechanisms of biosynthesis of intestinal mucins differ from those of other mucin-like glycoproteins that have been studied.

The effects of NC-1300 on gastric acid and mucus glycoprotein secretion were investigated in pylorus-ligated (4 h) rats. NC-1300 (30 mg/kg, intraduodenally) significantly inhibited gastric acid concentration more than 90 %. The agent did not affect the total mucus glycoprotein output in the gastric juice, but caused by about 1.5 times denser mucus glycoprotein secretion than that in the control group. The amount of mucus glycoprotein in the mucous gel layer increased by about 1.4 times with this agent. Thus, NC-1300 not only inhibits acid secretion but also promotes mucus secretion, and this may explain its ability to protect the stomach against necrotizing agents.

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Changes in gastric mucus glycoprotein (mucin) isolated from pirenzepine-treated rats with or without ethanol (50%)-induced gastric damage were studied. The prior administration of pirenzepine inhibited significantly and dose-dependently the occurrence of macroscopically observable hemorrhagic lesions induced by treatment with ethanol. The gastric mucosa was separated into the surface mucosa, including the mucus gel layer, and the deeper mucosa by mechanical scraping, and the mucin in each was isolated. In cthanol-treated animals the mucin content of the deep corpus mucosa was significantly reduced to 68% the control value. This reduction was inhibited by pretreatment with pirenzepine. In the surface mucosa mucin content was also reduced to 48% of control value by ethanol treatment, but pirenzepine pretreatment increased mucin content to 235% the control value. Total mucin content in the entire stomach essentially resumed the control level by pretreatment with 100 mg/kg of pirenzepine. A single oral administration of pirenzepine (100 mg/kg) caused no change in total mucin content, but mucin in the deep corpus mucosa selectively and significantly increased to 124% the control. These and the results of carbohydrate analysis of purified mucin indicate that pirenzepine administration possibly accelerates the secretion of accumulated deep corpus mucus, retains this deep mucus on surface mucosal mucus, and protects the gastric mucosa in ethanol-induced gastric damage. This may be related to the antiulcerogenic effects of pirenzepine.

Two siblings of a consanguineous marriage showed identical clinical features consisting of supranuclear vertical ophthalmoplegia, bradykinesia, rigidity. stooped posture, pseudobulbar palsy, and dementia, all beginning in the sixth decade. There was no history of encephalitis or of exposure to known chemicals. L-Dopa therapy was only partially and temporarily effective. Autopsy of one patient revealed extensive neurofibrillary degeneration with prominent involvement of the limbic system. There were no senile plaques or Lewy bodies. Under electron microscopy, there were paired helical filaments as well as 15-nm-wide straight tubules. The diffuse appearance of neurofibrillary tangles, predominant in the limbic system, and familial occurrence are unusual in progressive supranuclear palsy; these cases may, therefore, constitute a different, distinctive clinicopathologic disease.

Intraperitoneal (ip) injection of ketamine increased the concentration of dynorphin in the cortex of rat brain, while decreased it in the septal area. The affinity of ethylketocyclazocine (EKC) receptor binding was decreased in the cortex, but increased in the septal area after pretreating the rats with ketamine. This suggests that the dynorphin neuronal system is stimulated in the cortex and suppressed in the septal area by ketamine. In other 5 brain areas, ketamine had no effect on neither dynorphin concentration nor EKC receptor binding. As dynorphin was reported to produce seizure and spike discharge in the cortex while suppressed the hippocampal EEG of rat brain, it is likely that the dynorphin neuronal system may play at least a part in ketamine induced electrophysiological changes in the brain.

We have measured the de Haas-van Alphen (dHvA) effects of YbSn3, YbZn11and UGa2in the 4He temperature range up to 15 T. The results for YbSn3show that the dHvA frequencies range from 60 to 3000 T and the cyclotron masses from 0.13m0to 0.44m0, where m0is the free electron mass. For YbZn11the dHvA frequencies range from 200 to 11 000 T and the cyclotron masses are nearly the same as those of YbSn3. These results indicate that YbSn3is a compensated metal and Yb ions in YbSn3and YbZn11are divalent. The dHvA frequencies of UGa2range from 20 to 1300 T. The observed cyclotron masses range from 0.3m0to 3.3m0, which are larger than those of YbSn3and YbZn11by a factor of ten. Field dependence of the dHvA frequency is observed in the lowest frequency oscillations in UGa2. These results indicate that the 5felectrons in UGa2hybridize appreciably with the conduction electrons.