Besides clinically recognized lung cancers, a careful histological examination of the respiratory tract of autopsied men who were previously exposed to mustard-gas revealed significantly higher frequency of abnormal lesions including dysplasia and microscopical early cancer within the bronchial epithelium. These findings were encountered in not only individuals exposed to the gas and suffered later from clinical lung cancer, but also those exposed to the gas and suffered later from various diseases other than lung cancer, and also those not exposed to the gas but suffered from clinical lung cancer. Smoking effects appeared to be also significant in lung cancer development. According to the investigation of the Radiation Effects Research Foundation, the relative risk of lung cancer increased significantly with radiation dose in A-bomb survivors in Hiroshima and Nagasaki. Small-cell type lung cancer showed somewhat greater sensitivity than other types of lung cancer. An annual relative frequency of malignant mesothelioma in the major diagnoses of all autopsy cases has been increasing dramatically during the past 2 decades in Hiroshima district. The majority of examined cases with malignant mesotheliomas showed a significant accumulation of asbestos bodies within pulmonary alveoli. Ninety-nine per cent of our recent autopsy cases showed an intraalveolar deposition of asbestos bodies and proportional distribution of cases with dense exposure to asbestos appeared to be greater than previous investigations reported by others from other districts. Aforementioned unfortunate phenomena in regard with either chemical or radiation carcinogenesis, admonish us to be wise enough to make an urgent effort for the exclusion of such an exogenous carcinogenic agent as asbestos from our living circumstances.
1. From the necessity for long-term preservation of the chromosome-types found in annual Haplopappus gracilis (2n=4), studies on the cloning of this plant were carried out by some vegetative treatments including tissue culture. Hence a tissue cultured block named as shoot primordium was found in 1983. Botanical properties observed in the shoot primordium and its applications were summarized in this paper. 2. A shoot primordium is a dome-shaped tissue which occurs on the way to an adventitious shoot from tissue cultured cells of an explant in somatic life cycle. The shoot primordium proliferates self-propagating and forms a small mass of shoot primordia. 3. Properties observed in shoot primordia were described in the following way : external and anatomical morphology, cells, pattern of proliferation, somatic life cycle, superior stability in chromosome number, high ability to regenerate, ability of rapid proliferation, production of secondary metabolites and application to cryopreservation. 4. Applicative techniques developed up to the presents for the shoot primordia were outlined on the following subject : induction of shoot primordium, subculture and regeneration, induction of artificial mutation, isolation of free single cells, induction of somatic embryos, induction of shoot primordia from callus, and cryopreservation. 5. Shoot primordia could be induced successfully in 66 higher plants among 89 plants examined. It is found that the shoot primordia can be induced easily in most of the annual plants and in the perennial plants examined. It is also able to induce shoot primordia in some woody plants.
Evidence of the presence of monomeric heterocyclic N-imine is shown. Crystal structure of the titled compound revealed its characteristic construction including three classified molecular pairs in a unit cell. One of them was assembled with a couple of hydrogen bonds and other pairs were observed as molecular complexes. SCF-MO calculations were performed for this compound based on the crystallographic coordinates and suggested intermolecular interactions between the molecules. The nonbonded interactions were calculated by using van der Waals potential functions to discuss the thermodynamic stability of these complexes.
Isopropylidenation of maltitol by using excess 2, 2-dimethoxypropane (DMP) and p-toluenesulfonic acid in N, N-dimethylformamide at room temperature for 15 h yielded four acetals which were designated 1 to 4 in the order of decreasing Rf value on thin layer chromatography. After column chromatography on silica gel, compounds 1-4 were separated as 4, 6 : 1', 2' : 5', 6'-triacetal (1, 14%), 4, 6 : 2', 3' : 5', 6'-triacetal (2, 40%), 1', 2' : 5', 6'-diacetal (3, 4%), and 2', 3' : 5', 6'-diacetal (4, 12%), respectively. Excess DMP or prolonged reaction time results in an acetal migration from 1', 2'-to 2', 3'-positions. The reaction and the yields of 1-4 were investigated by high performance liquid chromatography analysis of the benzoylated acetals. 2', 3'-Di-O-benzylmaltose and 3-O-α-D-glucopyranosyl-β-L-gulopyranose were synthesized after chemical modification of 2 and 4, respectively. Thus, maltitol acetals have a potential value in the synthesis of disaccharides with an α-glycosidic linkage.
Synthesis, structure and reactions of 1, 2, 3-triazine 2-imines are described. In solution, a monomeric form is the stable form of the compounds which were synthesized from 1, 2, 3-triazines. The compounds were quaternized and acylated to give N-substituted derivatives. Diazotization resulted in deamination, and reaction with electrophilic acetylenes gave Michael-typed adducts together with bicyclic adducts.
Although a plasmid carrying long palindromic sequence can multiply in E. coli recB recC sbcB recF, it gets a deletion in the palindrome during the multiplicaiton. This deletion occurs at a specific small inverted repeat sequence present in the palindrome. Though the sequence specificity of the inverted repeat used for the deletion is not yet understood, more than four nucleotides seem to be recognized. The frequency of the deletion is higher when the sensitive small inverted repeat presents nearer to the junction of the palindrome to the vector plasmid.
An interconversion model which incorporated a first-pass metabolism was applied to the disposition kinetics for acetohexamide and its reversible metabolite, hydroxyhexamide, in the rat. Four fundamental clearances, CL10, CL12, CL20 and CL21 were calculated from four area under the plasma concentration-time curve values. Simultaneous computer multi-lines fitting of the plasma concentration-time data and adequacy of pharmacokinetic parameters in this model were tested by using an iterative nonlinear least squares regression program, MULTI.
The effects of age and apparent clearance (ACL) of phenobarbital (PB) concurrently administered as anticonvulsant(s) were studied in 651 epileptic children ranged with age from 2 months to 16.5 years old. ACL was calculated from the following equation; ACL=Dose (mg/kg/d)·F (bioavailavility of PB)/C (serum level of PB)·τ (dosing interval). F was assumed to be 1.0 and 0.8 for elixir and powder forms of PB, respectively. ACL of PB was significantly (p<0.05) correlated with age (r=0.590-0.741) in either patients taking PB alone or taking PB with other anticonvulsant(s). ACL of PB decreased with an increase in the age of patients. Mean ACL of PB in patients taking PB with sodium valproate or with more than two other anticonvulsants was significantly (p<0.05) smaller than that of patients taking PB alone, independent of groups subdivided with age. Neither phenytoin nor carbamazepine altered ACL of PB significantly. The serum level of PB should be monitored closely in pediatric patients taking PB with sodium valproate or more than two other anticonvulsants.
A method of high performance liquid chromatography for the determination of unchanged furosemide and its metabolites in the plasma and urine of human subjects is reported. A reversed phase Hibar Lichrosorb RP-8 column was applied to the present method. Furosemide from samples was extracted with diethylether. Beta-glucronidate of furosemide was determined after the addition of beta-glucronidase. 4-Chloro-5-sulfamoyl-anthranilic acid (CSA) was determined by the supernatant obtained from ten minutes centrifugation of the urine with ethanol. In the plasma and urine concentrations of unchanged furosemide of healthy volunteers, there were recognized differences among individuals. In patients with chronic renal failure, urine concentration of beta-glucronidate of furosemide increased in response to impairment of creatinine clearance. CSA could be detected only in the urine of patients receiving renal transplantation under a large dose administration of furosemide (above 200mg/d during rejection). And CSA does not seem to be an artifact product by the procedures of extraction. No interference could be observed by the drugs co-administered with furosemide. The present method can be utilized for a routine drug monitoring system of furosemide. Mechanism of formation of metabolites of furosemide should be further studied.
Aqueous solubility of menaquinone-4 (MK-4), a potent antihemorrhagic vitamin K2, largely increased with heptakis(2, 6-di-O-methyl)-β-cyclodextrin (DM-β-CyD), forming the higher-order complexes. By the analysis of phase solubility diagram, the stoichiometric ratio of the main complex was estimated to be 1 : 3 (MK-4/DM-β-CyD) with the stability constant of 46400M-1. Then, the 1 : 3 solid complex was prepared by the kneading method, and its dissolution, absorption, and pharmacological characteristics were compared with those of MK-4. The plasma levels of MK-4 after the oral administration to dogs and rats in the form of complex were significantly higher than the MK-4 alone, particularly in the cases of the fasted state and the lack of bile. When the complex was administered orally to rats under bile duct cannulation, MK-4 was absorbed through both portal and lymphatic routes. The oral administration of DM-β-CyD complex also attained the shortening of the blood-clotting time of MK-4 for warfarin-induced hypoprothrombinemic dogs. The enhanced bioavailability seemed to be mainly ascribable to the increase in dissolution of MK-4 by DM-β-CyD complexation.
Safflower (Carthamus tinctorius LINNE) has been traditionally used for the treatment of Oketsu, namely blood stasis in Chinese medicine. Aqueous extract from safflower inhibited the rabbit platelet aggregation induced by adenosine diphosphate. The sole inhibitor was isolated by high performance liquid chromatography (HPLC), and identified as adenosine by 13C- and 1H-nuclear magnetic resonance. As the result of quantitative analysis by HPLC using the capsule type C18 column, 16-550 ppm of adenosine were detected in safflowers collected from different districts.
The new method of iodine determination we developed consists of the following three techniques; oxygen flask combustion by using sample oxidizer, ion extraction with a phase transfer catalyst, and ion chromatography by using a routine ODS column; This method is applicable to measuring iodine not only in the blood, plasma, and urine, but also in the tissues and feces that are impossible to be measured by the conventional means.
The photoacoustic spectra of the powder mixture of methaphyllin with lactose and of acrinol and zinc oxide ointment were measured in the visible region. Linear relationships between relative photoacoustic signal and the concentration of drug were observed in the two systems. Each correlation coefficient of the regression line was more than 0.99. It is considered that photoacoustic spectroscopy is a useful method for the quantitative analysis of drug in the powder mixture and of drug in the ointment.
The purpose of this study was to investigate the relationship between the amount absorbed and the partition coefficient by using cinnamic acid in solutions with various pH solution. Cinnamic acid concentrations were measured by high-performance liquid chromatography. The partition coefficient of cinnamic acid between water and diethylhexyl phthalate, used as a plasticizer in polyvinyl chloride of the administration set, were measured at 30°C. The equilibrium absorbed amount of cinnamic acid was influenced by the pH of solutions. When the cinnamic acid concentration was 75 μg/ml in aqueous solutions, it was 1.05 mg/g at pH 1.23 and decreased to 0.63 mg/g at pH 3.96. And the calculated amount of cinnamic acid absorbed supposing that the equilibrium absorbed amount was in proportion to the apparent partition coefficient, was in good accordance with the experimental data.