Since 1969, authors have been doing a statistical analysis of airborne pollen grains, aiming at the clarification of their atmospheric behaviors, in connection with an increase in a number of pollinosis cases. The airborne pollens were collected three times a week starting from January 1 and ending December 31 with the help of cascade impactor, by which 600 l of air was suctioned at the rate of 51 per min for 2 h from 10 : 00 a.m. to 12 : 00 at the rooftop of one of the buildings (16 m high)in the Narashino Campus of Toho University, Funabashi, Chiba. The collected airborne pollens were numerated and classified under microscope according to the Ikuse's classification system for Japanese pollens. The number of days (n) was plotted as a function of daily number of a certain type of airborne pollens (x), not fitting to a simple normal distribution. However, the data were found to approximate a normal distribution when x was log-transformed as ln (x+1). Among the statistical methods tested, semilogarithmic plot, Weibull plot, Edwards' plot and circular graph method were found to be useful in the follow-up of seasonal variation of environmental pollen grains, especially when used in combination.
Application studies of radionuclides in pharmaceutical fields are described concerning two major categories, such as the use of γ-emitter in nuclear medicine and β-emitter in tracer investigation. In the former radionuclide an effort has been made to develop radioactive new diagnostic agents in the nephro-urology field. Of several agents examined two new radiopharmaceuticals, 99mTc-malic acid and 99mTc-dimercaptopropionic acid proved to be sufficient for renal imaging with adequate concentration in experimental animals and humans. Useful information was obtained for diagnosis of renal diseases using both the labeled agents. Identification and purity tests of radiopharmaceuticals also set forth for official compendia such as the Japanese pharmacopoeia and so on. In the latter one the fates of two medicines, thalidomide and norphenylephrine, were studied and the safety evaluation of some xenobiotics including food additives, plasticizers and domestic chemical products, etc. was carried out in animals using synthesized 14C- or 3H-labeled compounds. In addition, the metabolism of n-propyl-N-nitrosourea, a carcinogen, in rats, and chemical modification of high molecular substances such as DNA, RNA and proteins by 1, 1'-ethylene-bis(1-nitrosourea)(EBNU), a carcinostatic agent, were studied in vitro by the use of the tracer technique.
The nuclear matrix (nuclear scaffold), the RNA-protein skeleton of the nucleus, has a role in the organization and function of nuclear DNA. Nuclear processes associated with the nuclear matrix include transcription, replication, repair and splicing. We have purified a nuclear matrix protein, P130, which binds to several matrix attachment regions (MARs). Since the nucleotide sequence of P130 cDNA cloned by us was closely similar to that of matrin 3 cDNA cloned, except for two incorrect nucleotides within the matrin 3 coding region, and since the functions of matrin 3 were unknown, P130, referred to as P130/Mat3, was functionally characterized. The primary structure deduced for P130/Mat3 contained two DNA binding domains with C2H2-type zinc finger motif and two RNA binding domains. In addition, there were a nuclear localization signal and several phosphorylation sites for tyrosine or serine/threonine protein kinases, suggesting its multiple functions. MAR inserted upstream from the SV40 promoter in pMAR/luc assisted luciferase gene transcription in a transient expression system in Ac2F cells. Cotransfection of a plasmid carrying P130/Mat3 cDNA downstream from the CMV promoter into Ac2F cells produced this protein a level 4 times higher than that in wild-type Ac2F, causing 20 times higher luciferase activity from pMAR/luc than that induced by pMAR/luc alone. These findings indicated that MAR functions as a cis-element to which P130/Mat3 binds as one of the possible transactivators. Nuclear matrix proteins, which are tissue- and cell-type-specific, are altered with transformation and state of differentiation. We have shown that an MAR binding protein, P230, is detectable in rat hepatoma cells but not in normal liver, and suggested that this protein is a diagnostic and prognostic marker for liver cancer. It is clear that nuclear matrix proteins hold a considerable promise as diagnostic tools for pathologists. Present evidence, including our data, suggests that nuclear matrix proteins may be useful biomarkers of neoplastic disease in the serum, body fluids, and tissues. Nuclear matrix proteins are also potential candidates for the use as tumor prognostic factors and targets of anticancer drugs through apoptosis. We will discuss screening of drugs that interact with nuclear matrix proteins and influence nuclear events.
The fact that hemin can inhibit the mutagenic activity of compounds bearing polycyclic structures is ascribable to the ability of the porphyrin structure to complex with the planar surface of the mutagens. The elucidation of this mechanism has led to the discovery of copper phthalocyanine trisulfonate (cpt) as an efficient ligand to trap polycyclic compounds on polymeric supports that bear cpt through covalent bond linkages. In blue cotton, the support for cpt is cotton, in blue rayon, it is amorphous rayon, and in blue chitin it is poly-N-acetylglucosamine. Using these blue materials, we have successfully isolated mutagens of polycyclic structures, e.g., heterocyclic amines, from environmental complex mixtures such as food, urine, feces, and river water. Preparation and properties of these adsorbents are described. Chlorophyllin linked to Sepharose and chitosan is also described. The use of these green materials is discussed.
We have built a database for CARPIS(Case Reports of Adverse Drug Reaction and Poisoning Information System) since 1987, and the case reports of adverse drug reactions accumulated in the CARPIS database to be total about 20000. The purpose of our study is to develop, implement, and assess an estimation procedure for preventing the adverse drug reactions by subjective symptoms (complaints) of patients using this CARPIS. The case reports of the adverse reactions are not a systematical study and are elapse reports by the case, which encountered on the way of the cure. Therefore, it might be possible to use as the data if not gaining enough evaluation. Especially, the abstracts in the annual meeting of the society are fragmentary and does not often have objective evidence. Therefore, we contrived an original evaluation method and carefully selected the case reports for our study. Also, the adverse reactions are very colorful and it is difficult to handle them at once. Therefore, we study every organ and want to aim to make a finally all-round format. We reported on the Liver disorders, the Extra-pyramidal symptoms, the Drug eruption, the Leukopenia and so on. We discovered that there was an adverse reaction which shows very peculiar subjective symptoms (ex. Extra-pyramidal symptoms) and unpeculiar subjective symptoms (ex. Leukopenia). We want to show our point of view and the future of our study below.
The mechanism of the alteration in marble burying behavior-isolated housing (MBB-IH) mice was investigated. The determination of hypothalamus monoamine and serum corticosterone contents indicated that MBB-IH mice readily responded to the stress stimuli in conditioned fear stress. Six drugs, such as buspirone (10 mg/kg, p.o.), zimelidine (10 mg/kg, p.o.), clomipramin (10 mg/kg, p.o.), yohimbine (5 mg/kg, p.o.), ethyl β-carboline-3-carboxylate (β-CCE, 5 mg/kg, p.o.) and flumazenil (15 mg/kg, p.o.) were singly and/or three times administered to MBB-IH mice. Their inhibitory activity on the MBB-IH mice was considered by the use of activity profiles consisting of spontaneous locomotor activity, marble burying behavior and hypothalamus monoamine content. Using these profiles, we calculated the activities as vector in three-dimensional space, and compared the distance from the control point (DCP). DCPDOPAC and DCP5-HIAA were shortened by single administration of β-CCE and flumazenil. Oren-gedoku-to (30 and 300 mg/kg, p.o.) shortened the DCPDOPAC and DCP5-HIAA similarly to β-CCE. The blended crude drugs in Oren-gedoku-to, Coptis rhizome (636.0 mg/kg, p.o.), Scutellaria root (644.4 mg/kg, p.o.) and Gardenia fruit (894.8 mg/kg, p.o.) shortened the DCPDOPAC. Coptis rhizome and Scutellaria root also shortened the DCP5-HIAA. These results suggest that GABA neuron function intensely affects the alteration of MBB-IH and Oren-gedoku-to has the intrinsic benzodiazepine-like activity.
Objectives : The purpose of this study is to develop, implement, and assess an estimation procedure for preventing adverse drug reaction by subjective symptoms (complaints) of patients. This time, we focused and studied on drug eruptions. Methods : We have built a database for CARPIS (Case Reports of Adverse Drug Reaction and Poisoning Information System) since 1987, and the case reports of adverse drug reactions accumulated in the CARPIS database to be total about 20000. We studied 1473 cases of drug eruptions cumulated in CARPIS database. The evaluation scores were created based on the subjective symptoms and backgrounds of the patients. We estimated 1473 cases using this evaluation scores. Results : We could estimate 1455 cases (98.8%) in 1473 cases to be drug eruptions using this evaluation scores. The validity of this evaluation scores were sensitivity=98.8%, specificity=91.0% and predictive value of positive test=99.4%. The positive likelihood ratio was 11.0 and negative likelihood ratio was 0.01. Conclusions : This study confirmed the validity of our evaluation scores. We reported the evaluation scores about drug-induced liver diseases, drug-induced extra-pyramidal symptoms and drug-induced leukopenia before. In order to apply these evaluation scores to the clinical practice, we prepared an evaluation form for subjective symptoms and backgrounds of the patients with adverse drug reactions.
To determine l-ephedrine (E) and d-pseudoephedrine (PE) concentrations in human plasma simultaneously, we used a selected-ion monitoring method with gas chromatography-mass spectrometry (GC-MS) using deuterium-labeled E and PE as internal standards. The E and PE in human plasma were extracted with hexane-ethylacetate (9/1) under alkaline conditions and were easily converted into their heptafluorobutyryl derivatives by treating with heptafluorobutyrylimidazole. The calibration curves of E and PE showed a good linearity in the range from 0.82 to 81.9 ng/ml for E, and from 0.41 to 41.0 ng/ml for PE, respectively. the limit of detection was 0.82 ng/ml for E and 0.41 ng/ml for PE in human plasma, respectively.
Antifungal activity of Shikon, roots of Lithospermum erythrorhizon and Arnebia euchroma was investigated in vitro. The extracts containing the pigments of Ko-shikon or Nan-shikon showed the antifungal activities against Candida albicans. Acetylshikonin, one of these pigments, inhibited the fungal growth at MIC 15.6 μg/ml (RPMI24h) or 3.9 μg/ml (YNB24h).