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Evaluating airborne pollen concentrations is important for the understanding of the spatiotemporal dispersion of pollen grains. Using two identical pollen monitors in parallel, we performed two experiments in order to study the influences of a) the physical characteristics (orientation) of the air inlet and b) the presence of obstacles in proximity to the monitors on airborne pollen concentration data. The first experiment consisted of an evaluation of airborne pollen concentrations using two different types of orifices; 1) a vertically oriented inlet and 2) a wind vane intake, both attached to the same type of automatic pollen sampler. The second experiment investigated the relationship between vertical wind speed and horizontal wind direction around an obstacle with the goal of studying the impact of micro-scale wind on pollen sampling efficiency. The results of the two experiments suggest that the wind path near an obstacle might be redirected in a vertical direction before or after the wind flows over the obstacle, which causes measurement errors of airborne pollen concentrations that are proportional to the vertical wind speed, especially when a vertically oriented inlet is used.

The development of a simple and automatic pollen measurement methodology is required to manage allergic problems caused by airborne pollen. We developed a device and algorithm to automatically monitor airborne pollen by using basic laser optics technology. The device measures the sideward and forward scattering intensities of laser light from each particle. Because this device provides detailed temporal variation in the pollen concentration, the dispersal dynamics of airborne pollen can be effectively analyzed. We compared the pollen counts obtained with the automated method and standard Hirst-type method. Scatter-plot graphs were constructed of the forward and sideward scattering intensities of the observed particles. An extract window methodology was used to estimate the concentrations of the major allergenic pollens. The extract window parameters were obtained for major types of allergenic pollen. The results suggest the possibility of developing a device for monitoring several types of airborne pollen simultaneously. We determined the standard extract window to be used for estimating the concentration of all types of airborne pollen together. A field experiment was performed to evaluate the automated monitoring system with the standard extract window. The estimated temporal variation pattern of the total airborne pollen concentration agreed well with the observed temporal variation pattern for the whole pollen season. The pollen monitor was able to estimate the overall features of seasonal changes in the total airborne pollen concentration.

Key Clinical Message Central diabetes insipidus (CDI) results from a deficiency of arginine vasopressin (AVP) secretion. It is treated by replacement therapy with the synthetic AVP analogue desmopressin. To prevent heart failure in patients with CDI accompanied by cardiac dysfunction, controlling sodium and water intake is essential, using the minimum effective dose of desmopressin.

Background Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. Case presentation A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient’s postoperative course was unremarkable for > 7 years. Conclusions Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.

To examine the relationship between the scavenger receptor A (SRA) index (the number of SRA+ cells observed in 10 high power fields of peripheral blood (PB) smear samples; normal upper limit

Human immunodeficiency virus type 1 protease (HIV-1 PR) is an essential enzyme for the replication cycle of HIV-1. HIV-1 PR inhibitors have been extensively investigated as anti-AIDS drugs. For developments of HIV-1 PR inhibitors more promising than those utilized at the moment, the construction of reliable QSAR models that can elucidate the inhibitory mechanism as consistently as possible should be one of the most significant issues. Garg, Kurup, and their groups published comprehensive QSAR studies using past structure-activity data for HIV-1 PR inhibitors, and summarized some physicochemical structural factors of inhibitors that govern variations in the inhibitory activity for various structural types. There seem to exist much to be clarified further, especially for effects of electronic structure of inhibitors. It is also expected to incorporate structural and physicochemical information about the enzyme protein into the QSAR model. In this article, we reviewed our own QSAR study on a series of cyclic urea inhibitors with newly proposed QSAR descriptors. We performed molecular dynamics simulations of HIV-1 PR-inhibitor complexes to provide the accurate geometry to the fragment molecular orbital (FMO) calculations as well as to the estimation of an accessible surface area descriptor for inhibitors and amino acid residues. With the FMO procedure to cover full electronic feature of three-dimensional structure of protease-inhibitor complexes, we derived electronic descriptors for inhibitors and amino acid residues. The successful results are believed to provide a new insight into QSAR and understanding of binding mechanism of inhibitors with HIV-1 PR at atomic and electronic levels.

To investigate the efficacy and safety of bepotastine, we conducted a randomized, investigator-blind, placebo-controlled and parallel study to evaluate the allergic symptoms and the cognitive function of the subjects with Japanese cedar (JC) pollinosis in response to JC pollen exposure in an artificial exposure chamber.Twenty-four volunteers with JC pollinosis were enrolled in this study. The subjects were randomly divided into two groups: a bepotastine group and a placebo group (12 subjects each). Subjects received either a 10-mg bepotastine OD (orally disintegrating) tablet or a placebo 10 min before entering the chamber for a 3-h exposure. The nasal and ocular symptoms were evaluated by each patient at regular intervals. The amount of nasal discharge was measured and the number of sneezes recorded. To evaluate the cognitive function, a digit cancellation test (D-CAT), in which the subjects have to eliminate certain numbers within a fixed time, was conducted.Twelve subjects in the placebo group developed nasal and/or ocular symptoms, whereas six subjects in the bepotastine group showed none of the symptoms during exposure. Mean secretion weights and number of sneezes were significantly lower in the bepotastine group than in the placebo group. In D-CAT, no deterioration of work performance was observed in the bepotastine group. No adverse effects were observed in either group.Bepotastine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to JC pollen in an exposure chamber.

Background: An artificial exposure chamber (OHIO Chamber), which allows dispersal of a fixed concentration of Japanese cedar (JC) pollen under stable conditions, was constructed. This study was conducted to identify the exposure conditions assuring validity of the clinical tests conducted using this chamber. Methods: Twenty-four adult patients with JC pollinosis were exposed to different concentrations of JC pollen: 0 (only during the summer period), 4,000, 8,000 and 12,000 grains/m3, and the nasal and ocular symptoms were self-assessed during a 4-hour period of exposure. The amount of nasal discharge was measured and the sneezing frequency was recorded. This study was conducted twice during the summer and winter periods, i.e. non-pollen seasons. The reproducibility of the symptoms between the two seasons was assessed. Results: None of the subjects developed any symptom at the pollen concentration of 0 grains/m3. No significant differences in the time to the onset of symptoms were found between the summer and winter study, regardless of the pollen concentration. There were no significant differences between the summer and winter study in the total symptom score and total nasal symptom score at any pollen concentration, suggesting the very favorable reproducibility of symptoms. Conclusions: Efficient and reproducible results are obtained in patients exposed to JC pollen in the OHIO Chamber. The results suggest the conditions of JC pollen exposure have scientific validity and the OHIO Chamber has the potential to contribute significantly to basic and clinical studies of JC pollinosis.

Airborne pollen is important in relation to the social issues of pollinosis and of the environmental effects of genetically modified plants. Existing methods for pollen counting involve counting and classifying the grains that adhere to a sampling surface, requiring much time and skilled labor. We therefore have developed a method of automatically monitoring pollen, using a laser-optics instrument. In this instrument, the sideways and forward scattering of laser light by each particle is recorded in real time for computer processing. A field experiment was conducted in 2005, comparing our method with that of the older Hirst method. A scatter plot was made of the forward scattering vs. the sideways scattering for each particle. An algorithm was developed to find the optimum rectangular region of the plot for each type of pollen, and a count of points inside this region was taken as the count for that type of pollen. For the three most common types of pollen found in the field test (Urticaceae, Poaceae, and Ambrosia), the daily counts from this algorithm were compared with the daily counts from the Hirst-type (Burkard) sampler. There was a very high correlation (determination coefficient approximately 0.8) between the results of the two methods.

A 35-year-old Japanese woman was admitted with coma following flu-like symptoms. She was diagnosed with diabetic ketoacidosis and fulminant type 1 diabetes (FT1D) and received intravenous infusion of insulin and saline. The next day, the ketoacidosis disappeared, and she recovered consciousness. However, extensive ST-segment elevations in the electrocardiogram appeared with a positive troponin test, and the patient developed pulmonary edema on day 3. An echocardiogram showed globally reduced wall motion of the left ventricle and mild pericardial effusion. Despite medical therapy with intravenous furosemide, carperitide, and catecholamines, her cardiac function deteriorated rapidly, with the left ventricular ejection fraction decreasing to 26% within 7 hours, and progressed to cardiogenic shock that afternoon. The patient received mechanical circulatory support for 4 days with intra-aortic balloon pumping and percutaneous cardiopulmonary support, and recovered fully from circulatory failure. A paired serum antibody test showed a significantly elevated titer against parainfluenza-3 virus, indicating a diagnosis of fulminant viral myocarditis. She was discharged on multiple daily insulin injection therapy, and her subsequent clinical course has been uneventful. In summary, we present a case of concurrent FT1D and fulminant viral myocarditis. Parainfluenza-3 viral infection was confirmed serologically and was considered to be a cause of both the FT1D and fulminant myocarditis.

N-Isobutyl-N-(4-substituted benzyl)-4-halo-2-pentenamide 類はヒエに対し顕著な光要求性の除草活性を示す. ワタの幼植物およびそれより調製した酵素標品, ならびに培養した単細胞藻類を用いたアッセー系により, 殺草のメカニズムの解明を試み, 一連の供試化合物は明らかに protoporphyrinogen oxidase (PPO) 阻害活性を示したが, 植物毒性の強度変化は, むしろクロロフィル生合成阻害活性の強度変化によく対応した. したがって, 本系列の化合物の植物毒性には, PPOの阻害以外にクロロフィル生合成のほかの段階の阻害が重なっていることが示唆された.

Quantitative structure-activity relationships for insecticidal activity (against houseflies) and competitive activity against a specific [ 35 S]tert-butyl-bicyclophosphorothionate binding (to rat brain membranes) of some picrotoxinin-type 4-aminobutyric acid antagonists, including γ-BHC, endosulfan, bicyclophosphates, dioxatricyclododecenes and related compounds, were examined three-dimensionally using comparative molecular field analysis (CoMFA). The antagonists were classified into two series according to their molecular shapes: i.e. whether their structure was 'linearly' extended beyond the 'mast-head' position of the 'boat-like' skeletons (series 1) or not (series 2). The CoMFA showed that the slopes in steric and electrostatic fields around the molecule were significant for both series in governing the potency variations in insecticidal and binding activities. Hydrophobicity, a possible factor controlling transport behaviour of compounds, was significant in governing variations in insecticidal activity, but not for the case of the rat membrane binding. Assuming that there is a slight topological difference between series 1 and 2 compounds in terms of the mode of binding with the housefly receptor site, the insecticidal activity was analysable with a single equation for the combined set of compounds, but the rat membrane binding was not. The sterically and electrostatically favourable regions surrounding the molecular series indicated by CoMFA were roughly located at positions so as to interact with the binding subsites on the receptors proposed previously.

The purpose of this study was to investigate the incidence of multivessel coronary spasm and compare the clinical characteristics between patients with and without multivessel coronary spasm. In variant angina, it is controversial whether coronary hyperreactivity to vasoconstrictor stimuli is localized to a segmental lesion in only one coronary artery. Moreover, the clinical characteristics of patients with multivessel coronary spasm have never been investigated. Sixty-three patients (51 men and 12 women; mean age, 56 years; range 35-72 years) with variant angina and documented ST-segment elevation during a spontaneous attack underwent spasm provocation testing with selective intracoronary injection of ergonovine. All but 4 patients who experienced spontaneous attacks during cardiac catheterization had induced coronary spasm associated with ST-segment elevation and chest pain. Multivessel coronary spasm was found in 27 (43%) of 63 patients. By univariate analysis, a high frequency of angina (≥3 times/week), occurrence of a spontaneous attack within 24 hours after withdrawal of medication, a long history of angina and a progressive course of angina were significantly associated with multivessel coronary spasm. Multivariate analysis indicated a positive correlation between multivessel coronary spasm and progressive angina. Multivessel coronary spasm was found in 43% of patients with variant angina. Patients with multivessel coronary spasm have some unique clinical features. These results may increase the understanding of the pathophysiology and natural course of variant angina.

Background The role of coronary spasm in underlying disease-free patients who were resuscitated from sudden cardiac arrest remained uncertain. This study investigated the cause of cardiac arrest, and the etiologic and prognostic differences were compared between patients with underlying heart disease (group I) and those patients without underlying heart disease (group II). Methods Twenty-five survivors of sudden cardiac arrest were classified into two groups according to the presence or absence of underlying heart disease. To investigate the cause of cardiac arrest, we performed ergonovine testing and electrophysiologic study. Fifteen of the patients had underlying heart disease, while 10 did not. Results Electrophysiologic abnormalities were found in 13 of the 15 patients in group I. In group II, spontaneous attack of coronary spasm occurred in four patients during the observation period, and coronary spasm was induced in three of the remaining six period of 32 +/- 23 months, whereas no patients in group II had recurrence of sudden cardiac arrest at a median follow-up of 32 months (range, 10 to 72 months). Conclusions Electrophysiologic study identified a potential cause in 13 of 15 patients with underlying heart disease. Coronary spasm was involved in the pathogenesis of sudden cardiac arrest in survivors without identifiable underlying heart disease.

The authors present a case of methemoglobinemia due to accidental industrial exposure to nitric oxide gas. The patient showed severe generalized cyanosis on admission, although he had no other clinical symptoms. The arterial blood was chocolate-colored, and the concentration of arterial methemoglobin (Met-Hb) was as high as 45%. The serum and urine NO3- concentrations were 23 and 1, 443μg/ml, respectively. Continuous positive airway pressure (CPAP) mask therapy gradually decreased the concentration of Met-Hb. This was accelerated by intravenous methylene blue administration of 0.5mg/kg for 10 minutes. Arterial (SpO2) and mixed venous (SxO2) Hb-oxygen saturations were monitored using a pulse-oximeter and oximetric Swan-Ganz catheter, respectively. Blood samples were intermittently drawn to measure HbO2 (A) and HbO2 (V), by hemoximeter (Radiometer OSM-3). Pulseoximetry and mixed venous-oximetry could not differentiate Met-Hb from HbO2 or deoxy-Hb and overestimated HbO2 (A) and HbO2 (V) because they utilized only two light lengths. As the concentration of Met-Hb decreased, this overestimation was improved. When methemoglobinemia was severe, the assessment of Hb-oxygen saturation misrepresented the actual values of HbO2 (A) and HbO2 (V).

1. W-7, an anticalmodulin agent, prolonged the falling phase of the action potential in crayfish ( Procambarus clarkii ) giant axons, as did meta -methylbenzyl pyrethrate, a pyrethroid insecticide, and the methoxychlor of a DDT analog. 2. The anticalmodulin agent suppressed both the inward and outward membrane currents in the axon, measured under voltage-clamp conditions. 3. The pyrethroid and methoxychlor insecticides induced a large inward tail-current upon step repolarization, but the anticalmodulin agent did not induce a current of a detectable size.

The applicability of our new steric parameter for ortho substituents, Es(AMD), in evaluation of organic reactivity and physicochemical data was examined. The Es(AMD) constant was derived from the rate constants for acidic hydrolysis of ortho-substituted benzamides, and its scale was put as close as possible to that of the Es steric parameter of Taft, and Kutter and Hansch (TKH). For alkyl and halogen substituents, the Es(AMD) value was very close to the TKH Es value, but for methoxyl, isopropoxyl, and such planar π-bonded substituents as NO2 and Ph, it was not. Reactivity and physicochemical data taken from the literature were analyzed quantitatively by use of steric and electronic parameters, and the results obtained by Es(AMD) and Es were compared. The Es(AMD) value gave better results than TKH Es in various reactions including those of benzoic acids and their derivatives, if the change in the hybridization geometry of the reaction center between the initial and intermediate states was similar to that o...

The inhibition by N-(2,6-disubstituted benzoyl)-N′-(4-substituted phenyl)urea larvicides of the incorporation of N-acetyl-[1-14C]glucosamine, the precursor of chitin, into cultured fragments of the integument of Chilo suppressalis Walker larvae was measured in terms of the median inhibitory concentration with and without metabolic inhibitors. Variations in the activity index were quantitatively analyzed with physicochemical substituent parameters and regression analysis. The variations in the inhibitory activity of compounds in which ortho substituents on the benzoyl moiety were varied with a fixed substituent in the anilide moiety corresponded with the variations in their larvicidal activity. After separate consideration of the hydrophobic effect participating in transport processes, substituents in the anilide moiety showed peculiar electronic effects that depended upon the situation. Without an inhibitor of oxidative metabolism, the greater the inductive component of the electron-withdrawing property, the greater was the inhibition. This pattern resembled that found in earlier observations of larvicidal activity. With the inhibitor, the greater the total electrondonating property, including both inductive and resonance components, the greater was the inhibition. These results showed that the regular electron-donating effect of substituents in the anilide moiety is intrinsically favorable to the inhibition. Such an electronic mechanism as free-radical intermediate formation at the anilide moiety in oxidative metabolism may not be eliminated completely under the conditions used here for larvicidal activity measurement even with an inhibitor of oxidative metabolism.

Using a set of representative members selected from 4-pyridone-3-carboxanilides and ortho-chlorinated diphenyl ethers exhibiting light-dependent herbicidal activity, we examined the three-dimensional structure-activity relationships quantitatively. The most stable conformation of each compound, regarded as the ‘active conformation’, was determined by either semi-empirical or ab initio molecular orbital calculations. With a hypothesis defining a common substructural skeleton between the two different compound series. each molecule was superimposed. We first analysed the structure-activity relationship using an index for the substructure shape similarity according to the superimposed conformations. After finding the relevance of the hypothesis, we examined the three-dimensional structure-activity relationship using the comparative molecular field analysis procedure. The results suggested that the two different series of compounds have a common region of the receptor site. The variations in the light-dependent herbicidal potency were governed by hydrophobicty and three-dimensional steric and electronic field parameters of molecules participating in the transport process and the interaction with the receptor site. The result was consistent with that derived from our previous quantitative analysis with the use of free-energy-related substituent parameters and the traditional regression procedure for a large number of pyridone-carboxanilides.

The activity of a set of insect juvenile hormone (JH) mimetics was examined against the metamorphosis of Musca domestica, Spodoptera litura, and Nephotettix cineticeps [cincticeps] larva, the hatching of S. litura eggs, and the propagation of Aphis gossypi nymphs. The structures of the compounds were varied systematically in their dimensions and the position of a functional group. These 4-alkyl-, 4-alkoxy-, 4-benzyl-, and 4-phenoxyphenyl alkyl ether compounds had functions such as ether, oxime, hydroxylamine, ester, amide, carbamate, benzene, and pyridine in the alkane moiety (...)

Novel 4-pyridone-3-carboxanilide derivatives containing various substituents on the anilide benzene and 4-pyridone rings were synthesized, and their herbicidal activity against Echinochloa oryzicola was evaluated. These compounds exhibited light-dependent herbicidal activity, except for some 1-N-benzyl analogs substituted on the anilide moiety which were light-independent. Among compounds synthesized, 5-bromo-2′,6′-diethyl-1,4-dihydro-2,6-dimethyl-4-oxo-1-phenethylpyridine-3-carboxanilide was found to possess the highest light-dependent herbicidal activity, being almost equivalent with that of oxyfluorfen. The effects of substituents of the anilide benzene and 4-pyridone rings on the activity are discussed.

Potent herbicidal ethyl 5-[N-(5,7-dimethoxy-2H-1,2,4-thiadiazolo-[2,3-a] pyrimidin-2-ylidene) sulfamoyl]-1,3-dimethylpyrazole-4-carboxylate (I) was hydrolyzed under weakly basic conditions to afford a sulfonylurea (VII), a 2-pyrimidylcyanamide (IV) and a mercaptopyrazole (VI). The formation of these products was explained by nucleophilic attack at the 1 and 2-positions of the 1,2,4-thiadiazolo [2,3-a] pyrimidine ring. This is believed to mimic the process which occurs on application to the plant. I appears to be a pro-pesticide for the sulfonylurea, VII

We report a case of mesenteric hiatus hernia, together with a review of the literature. The case was a 10-year-old male complaining of abdominal pain. At admission the patient had a slightly distended abdomen with remarkable tenderness mainly around the navel. Blood examination revealed a severe leukocytosis. Abdominal simple X-ray films showed a gaseous shadow in the small intestine presenting with niveau. Perforation of acute appendicitis was suspected and emergency operation was carried out. During the operation, the patient was diagnosed as strangulated ileus due to mesenteric hiatus hernia, because the lower small intestine was strangulated and its freeing revealed a presence of a hiatus at the mesenterium approximately 100cm to oral side from the ileocecal region. Enterectomy was not employed and the hiatus was closed by suture. Postoperative course was uneventful. The patient could take foods by oral and was discharged.

The effect of structural modifications of 6-substituted N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamides on their anti-allergic activity was analyzed quantitatively by means of the Hansch-Fujita method. The activity of these compounds was correlated with hydrophobic (pi) and steric (molecular refractivity and STERIMOL B1) effects of the 6-substituent on the pyrazine ring. The 6-substituents with a length greater than n-propylamino possess an extra effect enhancing the activity. Moreover, the activity increased progressively from 6-non-amino via alkylamino- to dialkylamino-substituted compounds, other factors being equal. This could be attributable to an electronic effect of substituents. Electron-donating small and yet symmetric substituents with high hydrophobicity longer than n-propylamino seemed to be favorable to the activity. By compromising these contradictory requirements, small dialkylamino (including cyclic amino) groups were decided to be the most favorable substituents. This analysis was in agreement with the observation that the most effective compounds were the 6-dimethylamino (I-27) and 6-(1-pyrrolidinyl) (I-34) derivatives.

To evaluate the utility of the scavenger receptor A (SRA) index (no. SRA(+) monocytes observed in 10 high-power fields of peripheral blood (PB) smear samples, normal upper limit30) as the indication of disrupted, fissured, or eroded plaque, 225 patients with acute myocardial infarction (AMI), 79 with unstable angina (UA) and 91 with stable angina (SA) were examined. Thrombus was gathered from 95 of 205 sequential AMI patients (46.3%), and classified into platelets, mixed, and two kinds of residual mural thrombus (RMT). RMT was observed in 56 of 169 (33.1%) AMI patients with SRA indexor =30 at hospitalization. The SRA index of 82.4% of AMI, and 75.9% of UA, and 70.3% of SA patients wasor =30 at hospitalization. For 36 AMI patients who initially had an SRA index of30 at hospitalization, it exceeded 30 within 2 days, and the SRA index rapidly increased in most AMI patients after hospitalization. SRA(+) monocytes were considered to differentiate from SRA(-) monocytes in PB. An abnormally high SRA index is considered to be a useful indication of disrupted or fissured or eroded plaque.

Background: A pollen exposure chamber (OHIO Chamber) was built in central Tokyo, Japan, in order to study seasonal allergic rhinitis (SAR). Since satisfactory outcomes were obtained from the controlled pollen exposure at the chamber, we conducted preliminary studies in volunteers with SAR. Methods: Ten volunteers with SAR sensitive to Japanese cedar (JC) pollen were enrolled in this study. In order to investigate the intranasal and intraocular pollen number, volunteers were initially exposed to a low concentration of JC (2500 grains m 3 ) for at most 1 hour in this chamber. Before and after the exposure, nasal cavities and eyes were washed with 100 ml and 25 ml of saline, respectively. Nasal and eye washing solutions were collected and the number of JC pollen was counted. After 3 hours the volunteers were subsequently exposed to a moderate concentration of JC (4500 grains m3) for 2 hours. Subjective nasal and ocular symptoms were recorded and the amount of nasal secretion was measured during the allergen exposure periods. Results: During the initial exposure, all volunteers except one stayed in the chamber for 1 hour without any nasal or ocular symptoms. The number of pollen in the nose and eyes was 249.2 ± 120.9 and 13.6 ± 13.6 grains, respectively. During the subsequent 2-hour exposure to JC pollen, nasal and ocular symptoms developed gradually in a time dependent manner in all the volunteers except one. Conclusions: This is the first clinical study using Japanese cedar pollen under well-controlled conditions in the OHIO chamber in which the induction of allergic symptoms was observed. The OHIO chamber will be useful for studying allergic rhinitis in Japan.

A series of substituted hydroxyphenylureas was synthesized, the chemical structure of which was designed based on structures of natural antioxidants, vitamin E (α-tocopherol) and uric acid. They exhibited high inhibitory activity against lipid peroxidation. In order to gain an insight into the mechanism of the inhibition reaction, we analyzed their structure–activity relationships quantitatively. Electronic and steric effects of substituents on the phenolic hydroxyl group were shown to be of importance in governing the inhibitory potency. An increase in the electron donating property of substituents toward the phenolic hydroxyl group enhanced the antioxidative activity by the stabilization of an electron-deficient radical-type transition state. The steric shielding by ortho-substituents stabilized the phenoxy radicals formed following the transition state. Derivatives having the carboxyl group were only weakly active presumably because of an intermolecular ion-dipole interaction of the phenolic hydroxyl group with the carboxylate anion which could retard the formation of the transition state.

Previous QSAR (quantitative structure-activity relationships) examples of steroid hormones were briefly surveyed. The absorption and distribution processes and pharmacological activities in which transport factors are critical are governed mainly by molecular hydrophobicity. When the expression of the overall biological activity is controlled by the binding-affinity with the receptor sites as the rate-limiting process, the QSAR pattern is more complicated, because stereoelectronic and hydrogen-bonding effects of substituents or substructures of the molecule are usually involved in the structure-affinity relationships. The binding affinities of a number of androstan-17β-ols and estratrien-17β-ols for androgen and estrogen receptor preparations were experimentally measured and their structure-affinity relationships were analyzed using classical and three-dimensional (CoMFA) QSAR procedures. The regiospecific stereoelectronic properties of the molecule were found to significantly regulate the affinity in each pair of combinations between ligand and receptor species. The hydrophobicity was of minor importance. The classical and CoMFA procedures were complementary to each other, illustrating the “components” involved in physicochemical and structural requirements for the binding affinity. The structural features of epitiostanol, an, antiestrogen, which is an androstanol derivative that has been marketed as an anti-breast cancer agent, agreed very well with the QSAR patterns from the two procedures.

Structural variations from agonists to their selective antagonists seemed to follow certain patterns. To analyze the variation patterns in the structural modification processes in past examples as well as to utilize the “common” variation patterns as possible principles to design new selective antagonistic drugs, the structures of agonists and their antagonists were superimposed on a two-dimensional grid template composed of regular hexagons and the topological similarities and dissimilarities of substructural elements between agonists and antagonists were examined. Between several pairs of neurotransmitter amines and their “selective” antagonists, similar patterns were disclosed in their structural modification processes. The generalized structural modification patterns were successfully applied as guiding principles to design and identify a new prototype structure of the 5-HT3 antagonist. The prototype structure was optimized by use of QSAR procedures leading to a compound which shows a potent antiemetic activity as well as a powerful gastrointestinal-motility modulation.

The effects of substituted benzyl (1R)-trans-chrysanthemates and related compounds on the action potential of the crayfish giant axon were investigated using an intracellular microelectrode. The effects are broadly classified into three types: deceleration of the falling-phase of the action potential (type A), elevation of the depolarizing after-potential (type B), and the combination type (type C). The potency of the type A compounds to decelerate the rate of the falling-phase was determined in terms of the concentration required for reducing the rate to a specified degree. This potency was shown to correlate with the potency to induce repetitive discharges in the cockroach central nerve cord in terms of minimum effective concentration, which was determined previously. The potency of the types B and C compounds to elevate the after-potential was, however, not related directly with the cockroach nerve repetitive activity. The elevation of the after-potential is one of the critical factors but other effects such as a depolarization of the resting potential may be involved in determining the repetitive activity.

An enzyme preparation from the homogenate of American cockroach heads [Periplaneta americana (L.)] converted tryptamine hydrochloride to a toluene-extractable material. Optimum conditions for the reaction were obtained with 0.3 M sodium phosphate buffer, pH 6.6, at 30°C. The enzyme was very unstable. Its activity was scarcely inhibited by such typical monoamine oxidase inhibitors as iproniazid phosphate and tranylcypromine hydrochloride. Enzyme activity was not affected by the addition of NADPH2, but was accelerated by acetyl coenzyme A or coenzyme A. A main product of the enzymic reaction was isolated and identified as N-acetyltryptamine by chromatography and spectroscopic analyses, which suggests that the enzyme is a kind of N-acetyltransferase.

The interaction of penicillin with high molecular components of plasma expander such as dextran, 6-hydroxyethylstarch, and polygeline were studied. The formation of penicilloyl polysaccharides and smaller amounts of penicilloyl polygeline during incubation were confirmed by ultrafiltration and gelfiltration. The ultrafiltration through Collodion-Bags SM 13200 was found to be a rapid and convenient method for the determination of macromolecular penicilloates. The accelerated degradation by the formation of penicilloyl esters with glucose and lactic acid was also suggested.

さまざまな化学構造をしたピレスロイドやDDT, メトキシクロルは, ザリガニ腹部中枢神経において観察される自発性放電頻度を著しく高めた. この生理活性の強さは化合物との処理温度に依存し, 約25℃で最大の活性を示したが, このような活性に対する温度効果は軸索の興奮活性におけるものとよく一致した. 多くのピレスロイドは, ザリガニ中枢神経巨大軸索の静止電位を脱分極させる作用をも示したが, この活性は自発性放電の増強活性より低かった. しかし, 両活性間にはある程度の相関性があり, これらの作用機構が共通のものであることを示唆するものと考えられる. 殺虫剤によって誘起された高頻度の自発性放電は薬剤との処理開始後2時間以上も持続したが, 外部からアセチルコリンを投与した場合には頻度は一時的に大きく増加したものの, その後間もなく処理前のレベル以下にまで低下した. また, 殺虫剤によって高められた自発性放電の頻度は外部より投与したGABAによって抑制された. このような結果から, ピレスロイドやDDTが自発性放電の頻度を高める効果をもたらす作用点を, 軸索, シナプス部位に分離して考察した.

Domoic acid and related compounds isolated from a red seaweed, Chondria armata , were strongly insecticidal toward various insects and also caused contraction of the hindgut excised from American cockroaches. The contraction of the hindgut did not occur when calcium ions were removed from or when a calcium channel blocker, verapamil, was added to the incubation medium. The addition of a cysteine proteinase inhibitor, strepin P-1, partially blocked the domoic acid activity. A low concentration of domoic acid enhanced the sensitivity of the insect neuromuscular junctions to glutamic acid. These results suggest that domoic acid not only affects calcium ion transport and stimulates a calcium-dependent process that regulates the release of glutamic acid from presynaptic nerve endings, but also acivates a calcium-dependent proteinase leading to generation of glutamic acid receptors on the neuromuscular postsynaptic membrane from the latent state. Proctolin, a neuropeptide of insects, also caused contraction of the hindgut. As with domoic acid, the proctolin-induced contraction did not occur without calcium ions in the incubation medium or after treatment with verapamil. It was also partially blocked by strepin P-1. Thus, proctolin is probably a natural regulator of signal transmission of the neuromuscular junctions of the insect hindgut, and domoic acid may bind to proctolin receptors to act.

The patient, a 61-year-old man, was diagnosed as having gastric cancer and underwent subtotal gastrectomy in 1979. In histopathological diagnosis, the tumor was a well differentiated tubular adenocarcinoma. An isolated shadow was found in the right and lower lung field during postoperative observation, and the patient was admitted to our hospital. After scrupulous examination, esophageal cancer was discovered by fluoroscopy of the upper digestive tract. Excision of the thoracic esophagus and the right and lower lung lobe was performed in August, 1983. With regard to esophageal reconstruction, interposition of the upper transverese colon in the ileocecum via the posterior sternum was performed. In histopathological diagnosis, the tumors were classified to be a well differentiated squamous cell carcinoma in the esophagus and a moderately differentiated papillary adenocarcinoma in the lung, and these were diagnosed as triple cancer according to the definition of Warren and Gates et al. The patient died of metastasis of the esophageal cancer to the liver in May, 1984.

Juvenile hormone mimetic activities on Aedes aegypti (yellow-fever mosquito) and Tenebrio molitor (yellow mealworm) of compounds having (2E,4E)-3,7,11-trimethyl-2,4-dodecadienone structures were comparatively and quantitatively analyzed in terms of their physiochemical structural parameters and by regression analysis. They were structurally composed of three classes, ester and thiol ester derivatives, amides, and ketones, depending on the C1 substituents. The results indicated that the steric dimensions and the hydrophobicity of the whole molecule are important factors in governing the activity through these classes as well as through both insect species. The effects of the structure of the C1 and C11 substituents, the two ends of the chain molecule, are specific to the insect. The length along the bond axis of the C1 substituents is significant and the hydroxy and alkoxy functions attached to the C11 atom favor the activity on A. aegypti, whereas with T. molitor the width of the C1 substituents in the direction perpendicular to the bond axis is significant and the position-specific hydrophobicity of the C1 moiety enhances the activity. The activity is also affected differently by the compound types. The amide and ketone series of compounds are more active than the corresponding ester type of compounds on T. molitor, while the favorable types on A. aegypti are the ester and ketone derivatives. Correlation equations formulated for 85 active compounds on A. aegypti and 84 compounds on T. molitor led us to draw a hypothetical "mode of action" model for each species, which visualizes the overall similarity as well as the species differences of the interaction site or the receptor and may show the structural conditions necessary for activity.

Twenty-five synthetic pyrethroids and related chemicals were assessed for their effects on the uptake of Ca 2+ (as 45 Ca 2+ ) by crude homogenates prepared from crayfish ( Procambarus clarkii ) nerve cords and 20 were assessed on the uptake by homogenates prepared from lobster ( Panulirus japonicus ) axons. A parabolic relationship was demonstrated between inhibition of Ca 2+ uptake for this series of chemicals and lipophilicity (log P ) in both species when tested at 5 μ M . Optimal log P for maximal inhibition was located at about 6.6 and 84(±6)% inhibition was obtained with resmethrin. Compounds of higher or lower log P were either weaker inhibitors, not inhibitors or occasionally resulted in slightly increased levels of Ca 2+ uptake. No direct correlations between the potential for the pyrethroids to inhibit Ca 2+ uptake and the potential for these agents to increase the frequency of spontaneous discharges in crayfish nerve cords, to induce repetitive firing in American cockroaches, or the lethality to cockroaches or to any other neurophysiological or toxicity parameter could be established. It was concluded that although some synthetic pyrethroids are moderately potent inhibitors of Ca 2+ uptake into nerve cord and axonic preparations (i.e., I 50 for trans -resmethrin equals 1 μ M ) this inhibition alone does not relate to the neurophysiological changes in isolated nerve preparations or to the toxicity of these agents in insects.

The kinetics of the degradation of cefotiam in aqueous solution was studied at 25°C and an ionic strength of 0.6 over the pH range of 2 to 12. The degradation was a pseudo first order reaction in this pH range. The rate-pH profile showed a characteristic maximum near the isoelectric point of cefotiam (pH 5.8). The optimal pH of an aqueous solution of cefotiam dihydrochloride for stability was calculated to be 8.0. The degradation pathways were shown to involve spontaneous hydrolysis of four ion species and hydroxide ion-catalyzed hydrolysis of the monoanion. Aminoglycosides accelerated the degradation of cefotiam by a pseudo second order reaction. From analysis of the rate-pH profile of the second order rate constants of these aminoglycosides, it appeared that the reaction was substantially a third order reaction with regards to cefotiam, aminoglycoside and hydroxide ion. Therefore, the combined use of cefotiam and aminoglycosides should be avoided at alkaline pH and/or at high concentration.

A series of aralkyl and alkyl carbamates of the type R1OCONR2R3 (R1=alkyl or aralkyl, R2, R3=H, Me, Et) were prepared and tested for anticonvulsant activity in mice by means of the maximal electroshock seizure test. The ED50 values were analyzed in terms of hydrophobic (log P), electronic (σ1) and other parameters by regression analysis. The results are essentially the same as those for previously studied m-and p-substituted benzyl N, N-dimethylcarbamates (X-C6H4-CH2OCONMe2). The activity depended parabolically on log P with an optimum log P of 1.7, and was negatively correlated with σ1. It was also found that the potency is reduced when R1 is an alkyl group or includes a hydrogen-bonding group. Structural requirements for the optimal potency and the aromatic ring contribution to the activity are discussed.