Banding growth in liquid media exhibited by mutants in orthophosphate repressible cyclic phosphodiesterase, cpd-1 and cpd-2, was found to be due to the alternate appearance of submerged mycelia and submerged conidia. Thus cpd-1 and cpd-2 exhibited rhythmic conidiation both in liquid and on solid media, which indicated the persistence of circadian rhythm in liquid media. The examination of the levels of cyclic 3', 5'-AMP in wild type, cpd-1, cpd-2 and band (bd) strain revealed rhythmic oscillations in cyclic 3', 5'-AMP levels with period lengths of about 24hr. Conidiation on solid media took place 2-3hr after the appearance of a major peak of cyclic 3', 5'-AMP.

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We have developed a cross-linked positive-tone resist, called the Suppressed Aggregate Extraction Development Resist (SAGEX), for the purpose of reducing the line-edge roughness (LER) in resist patterns, which is caused by the existence of polymer aggregates in resist films. Some aggregates are extracted during development, but those remaining embedded on the pattern sidewall cause the LER. To suppress such aggregate extraction development, we fix the aggregates by cross-linking their surrounding polymers in advance before exposure and development. The cross-linking does not greatly affect the exposure reaction by electron-beam. The SAGEX resist made by the cross-linking indicates reduced LER in addition to fine patterning.

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We investigate the linewidth fluctuation in resist patterns, which is a serious problem in electron beam nanolithography. Granular structures with a diameter of 20-30nm have been observed in resist films. We have determined that these structures cause the linewidth fluctuations. The granules are made up of polymer aggregates. We discuss the origin of the aggregates from the point that their size depends on the polymer molecular weight. We also show that linewidth fluctuation is reduced when the pattern size is less than the aggregate size. The linewidth dependence of the linewidth fluctuation can be explained by the influence of the resist polymer aggregate on the development behavior.

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In an effort to locate medullary structures that mediate the renal-sympathetic reflex, the effect, on the excitatory (E) and inhibitory (I) components of that reflex, of certain drugs applied to the ventral surface of the medulla was investigated in urethane-anesthetized and vagotomized rabbits. Application of bicuculline, a GABA receptor antagonist, selectively abolished the I component of the renal-sympathetic reflex as well as the sympathoinhibition elicited by stimulation of the aortic nerve. The E component, on the other hand, was specifically eliminated by kynurenic acid, a glutamate receptor antagonist. Strychnine or atropine sulfate did not affect either reflex appreciably. Subsequently, within the region of the ventrolateral medulla (VLM) subjacent to the site of drug applications, we searched for neurons which responded to stimulation of the renal nerve and/or the aortic nerve. Of 68 responsive VLM neurons found, 50 (73.5%) responded to stimulation of both nerves. Of the 50 neurons, 40 were tested for their antidromic activation to stimulation of the spinal cord. Twenty-four neurons (60%) were antidromically activated. Responses of these reticulospinal neurons to stimulation of the renal nerve preceded that of renal nerve activity (RNA) by about 100ms. All the antidromically activated, VLM neurons which responded to stimulation of the renal nerve also responded to stimulation of the aortic nerve. In conclusion, the renal-sympathetic reflex appears to be mediated by the same pool of bulbospinal neurons in the ventrolateral medulla that mediates the arterial baroreceptor reflex, and the E and I components of that reflex can be selectively abolished by pharmacological intervention of the subjacent ventral surface of the medulla.

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In urethane-anesthetized and vagotomized rabbits, electrical stimulation of the afferent renal nerve (RN) elicited reflex changes in renal nerve activity (RNA) and arterial pressure (AP). The responses were attributable mostly to excitation of nonmyelinated afferent fibers, although in about 30% of the animals, they were contributed slightly by myelinated afferents. In about 70% of rabbits, the peristimulus time histogram (PTH) of RNA following stimulation of the RN consisted of a long-lasting inhibitory (I) component occasionally accompanied, during its recovery phase, by a transient excitatory (E) component. In these animals, tetanic stimulation of the RN resulted in a depressor response, either alone or, if an E component was present in the PTH, followed by a slight pressor response. In the remaining rabbits, the PTH was composed exclusively of an E component and tetanic stimulation caused a pressor response. Stimulation of the RN evoked reflex changes in cardiac sympathetic discharges comparable to that of RNA, whereas the change in cervical sympathetic discharges was much smaller. The sympathetic response remained intact after a total transection of the rostral medulla near the ponto-medullary junction; the I component was even augmented. However, it usually disappeared following a transection at the high cervical cord. Bilateral lesions of the nucl. tractus solitarius (NTS) near the obex failed to appreciably affect the response. Among chemical and mechanical stimuli examined, nociceptive stimulation of the kidney elicited a sympathetic response comparable to that following nerve stimulation In conclusion, the renal-sympathetic reflex in rabbits (1) originates predominantly from nonmyelinated afferent renal fibers activated effectively by nociceptive stimulation applied to the kidney; (2) depends critically on medullary structures other than the NTS; and (3) evokes changes of the same temporal pattern but of nonuniform magnitude in sympathetic discharges to different organs.

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In 55 anesthetized and paralyzed adult rabbits, 161 spontaneously active neurons which responded to electrical stimulation of A-fibers of the aortic nerve were found within the ventrolateral medulla (VLM). They were termed barosensory VLM neurons, since the aortic nerve A-fibers were considered to consist exclusively of afferents from arterial baroreceptors. Forty percent of barosensory VLM neurons tested (49/123) were activated antidromically by stimulation of the dorsolateral funiculus indicating that they send descending bulbospinal projections. Spontaneous discharges of barosensory VLM neurons were invariably inhibited by stimulation of aortic nerve A-fibers. Ninety-three percent of 80 neurons tested also responded to stimulation of aortic nerve C-fibers, a mixture of barosensory and nonbarosensory afferents. Natural stimulation of carotid sinus baroreceptors by an intravenous injection of phenylephrine in 19 vagotomized rabbits with aortic nerves disrupted inhibited spontaneous activity of all the 50 barosensory VLM neurons tested. By contrast, pharmacological stimulation of right or left carotid body chemoreceptors by close arterial injection of NaCN into the carotid sinus augmented activity of 93% of barosensory VLM neurons tested (41/44). The neuronal response was always greater to stimulation of chemoreceptors in the contralateral carotid sinus. Seven out of 8 barosensory VLM neurons tested (88%) were orthodromically excited by stimulation of the posterior hypothalamic area. In 74% of the 97 neurons examined in 29 vagotomized animals, a distinct respiratory-related rhythm, locked to that of phrenic nerve activity, was discerned. Thus, spontaneous activity of barosensory VLM neurons is inhibited by afferent inputs from aortic and carotid sinus baroreceptors, but is excited by incoming signals from carotid body chemoreceptors and the posterior hypothalamic area. It is also subject to the influence of the central mechanism generating the respiratory rhythm.

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The properties of carnosine (Car) and glycylglycine (Gly-Gly), transported across the mucosal border, were studied in isolated guinea pig everted ileum. The initial influxes of both dipeptides could be described by single Michaelis-Menten kinetics, having a nearly equal value of maximum influx. Mutual inhibition studies showed that the inhibition observed between Car and Gly-Gly was fully competitive, indicating that both Car and Gly-Gly share a common carrier. Although carrier-mediated influxes of the dipeptides were independent of Na⁺, the addition of the dipeptides into the mucosal solution evoked sudden and sustained increments of mucosal negativity. The changes in short-circuit current (ΔI_sc) evoked by the peptides increased as the Na⁺ concentration in the solution was increased, although both dipeptides evoked small increases in I_sc, even in the absence of Na⁺ In spite of these common properties of transport and transport-related electrical phenomena, it was seen that the maximum change in transmural potential difference (ΔPD_{t max}) evoked by Car was about half that of Gly-Gly. Such a discrepancy between coincident J_max values and values of ΔPD_{t max} suggests that the mechanism of induction of ionic flow is different for these two dipeptides.

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The influx of L-glutamate or L-aspartate across the intestinal brush border membrane was absolutely dependent on the presence of Na⁺ in the mucosal solution and saturable. The addition of these amino acids into the mucosal solution induced a sudden and sustained increase in the transepithelial potential difference (PD_t), which was found to be absolutely dependent on the presence of Na⁺ in the mucosal solution. The increases in PD_t induced by L-glutamate or L-aspartate conformed to Michaelis-Menten kinetics against the concentration of each organic substrate. On the other hand, the relationship between the change in short-circuit current induced by acidic amino acid and Na⁺ concentration did not conform to Michaelis-Menten kinetics but was sigmoid. A kinetic study indicated that 2 Na⁺ were translocated per molecule of the acidic amino acid. The PD_t was not altered by the total replacement of K⁺ by Na⁺ in the mucosal solution and showed the optimum pH at around 7. The transfer of L-glutamate from mucosal to serosal solution was examined with everted sac of ileum. A significant increase in serosal appearance was observed for L-glutamate and L-alanine after the incubation with L-glutamate. The serosal appearance of L-glutamate was unaffected by the presence or absence of HCO₃^-.

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We designed highly selective non-peptide agonists for the δ-opioid receptor. On the basis of the "message-address" concept in this field and the accessory site hypothesis, a novel class of hetericycle-fused octahydroisoquinoline derivatives were synthesized. One of these compounds (4aS^*, 12aR^*)-4a-(3-hydroxyphenyl)-2-methyl-1, 2, 3, 4, 4a, 5, 12, 12a-octahydropyrido[3, 4-b]acridine, TAN-67 (2)] showed high selectivity for the δ-opioid receptor (K_i=1.12 nM) in guinea-pig cerebrum with a 2070-fold lower affinity for the μ-opioid receptor and a 1600-fold lower affinity for the К-opioid receptor. TAN-67 was a potent δ-opioid receptor agonist with an IC₅₀ value of 6.61 nM in the mouse vas deferens assay that was reversed by naltrindole (NTI) (K_e=0.21). Moreover, TAN-67 was shown to have antinociceptive activity following subcutaneous administration in the mouse acetic acid abdominal constriction assay that was antagonized by NTI (δ₁-and δ₂-antagonist) and 7-benzylidinenaltrexone (δ₁-antagonist), but not by naltriben (δ₂-antagonist). This systemically applicable non-peptide agonist will be useful for elucidating the pharmacological properties of the δ-opioid receptor.

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Early gastric cancer usually has a good prognosis following surgical treatment. However a small number of cases show extensive metastases to distant organs. We here report an unusual case of early gastric cancer detected by bone metastasis. An 81-year-old Japanese woman was referred to our hospital with a right ileac tumor, biopsy of which turned to be well-differentiated adenocarcinoma. After checking for the primary lesion, early gastric cancer with IIa type was determined by both upper gastrointestinal series and gastrofiberscopy. CT scan revealed lymph node swelling around the celiac artery, which was considered to be the cause of her epigastralgia. After radiotherapy for the iliac bone metastasis, subtotal gastrectomy was performed with the intention of relieving her epigastralgia. Although she could return to her ordinary daily life after the operation, regrowth of the iliac bone metastasis, paraaortic lymph nodes metastasis and multiple lung metastasis lead to her death nine months after the operation. Bone metastasis from gastric cancer is clinically rare, especially in early gastric cancer. Although no effective treatment for such intractable disease is established, it is expected that a new strategy combining surgery, chemotherapy and radiotherapy may improve the prognosis and QOL of patients.

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Young guinea pigs were fed a semipurified diet low in selenium (Se) and phospholipid. The blood Se and tissue glutathione peroxidase activity were lowered, electrocardiogram and ultrastructure of the myocardium appeared abnormal, and tissue chromolipids were elevated in guinea pigs fed with this basal diet. Diminished changes, however, occurred in groups receiving supplemental Se. Supplementation of Se resulted in maintenance of the normal level of total phospholipid and the ratio between different phospholipids in the cartilage (Acta Pharmacol. Sinica, 5 (1984) 264-267), but in the heart the ratio was improved only when adequate phospholipid (especially endogenous phospholipid) was given simultaneously. Activity of the membrane binding enzyme was slightly restored by Se supplementation. Only when both phospholipid and Se were given sufficiently did the cytochrome oxidase activity in myocardium and cAMP level in plasma increase markedly, even more than that of the control group.

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Recently, rapid developments in mass spectrometry have enabled people who do not have adequate knowledge of chemistry to operate mass spectrometers. In addition, some sales engineers dealing with mass spectrometers have little knowledge of chemistry because they did not major in chemistry, when in university. However, knowledge of chemistry and mass spectrometry is necessary to obtain optimum results and to highlight the favorable points of their instruments. In this paper, we present some knowledge of chemistry and mass spectrometry as a short tutorial course for the abovementioned persons.

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