[Down-regulation of liver regeneration by LAK cells--a study for effect of neuraminidase treated LAK cells on liver regeneration]. Both effect of LAK cells and neuraminidase treated LAK (N-LAK) cells on liver regeneration were investigated after 70% partial hepatectomy in mice. Intravenous transfusion of LAK cells suppressed the liver regeneration depending on cell numbers injected. N-LAK cells accumulated into regenerating liver 1.7 times in cell number compared with LAK cells. Injection of 5 x 10(7) LAK cells and N-LAK cells into hepatectomized mice suppressed the liver regeneration by 16.5% and 53.8% respectively. These results indicated that suppression of the liver regeneration by LAK cells was dependent upon the number of injected LAK cells and the degree of accumulation of LAK cells into the liver, namely, LAK cells down-regulate the regeneration of liver cells in the micro-milieu.


[Treatment of hemobilia after percutaneous transhepatic cholangiography and drainage (PTCD)]. PTCD was performed in 206 of our patients during the past 6 years and 7 months. Of the 206, hemobilia occurred in 14 patients (6.8%). The hemorrhage was completely stopped by irrigation of the bile duct in 3 patients, compression with a larger catheter in 7 patients, and transcatheter anterior embolization (TAE) in 4 patients. TAE was performed on the patients whose hemobilia could not controlled by the compression with a larger catheter. In TAE, either a steel coil or a sponge was used as an embolus. Rebleeding occurred in one patients for whom the right hepatic artery was chosen as a embolization site. Therefore, it was decided that the embolization was going to be done in all the hepatic arteries when the blood stream in the portal vein and preserved functions of the liver of the subjected patients including the one with rebleeding were fully normal. A complete control of the hemorrhage was obtained in all patients. The PTCD root caused hemobilia was removed after TAE in considering the possibility of rebleeding from the root, and a new PTCD root was made.


[Studies on the influence of long-term doses of lipid peroxide generators on rat pancreas]. The role of oxygen derived free radicals or tissue lipid peroxides in the pathogenesis of chronic pancreatitis has not been established. To evaluate long-term effects of tissue lipid peroxides in the pathogenesis of chronic pancreatitis, we treated Wistar male rats with 2,2'-azo-bis-(2-amidino-propane) dihydrochloride (AAPH) and/or linoleic acid (LA) for 3 or 6 months. Rats were divided into eight groups. A: Saline-treated rats for 3 months as control, B: AAPH 40 mg/kgw intraperitoneally, twice a week for 3 months, C: LA 0.5 ml/kgw intraperitoneally, every other week for 3 months, D: AAPH and LA for 3 months, E: Saline-treated for 6 months, F: AAPH for 6 months, G: LA for 6 months, H: AAPH and LA for 6 months. The results were as follows: Lipid peroxide contents of the pancreas were elevated in groups: C, D, G and H. Histological examination revealed epithelial hyperplasia of large pancreatic ducts, vacuolization of ductal epithelium, intraepithelial neutrophilic infiltration, periductal mononuclear cell infiltration (ductulitis and peri-ductulitis), and sporadically in the lobules, destruction of acinar cells, neutrophilic infiltration and ductular proliferation in the same groups. These findings indicate that tissue damage was more severe in the pancreatic ducts than in the acinar cells, however no damage was seen in the endocrine pancreas. Vitamin E content of the pancreas was decreased in groups: B, C, D, F, G and H. Tissue glutathione peroxidase (GSH-Px) activity was increased in groups: D and H. Tissue catalase activity was increased in groups: D, G and H, but no change of superoxide dismutase (SOD) activity was seen in any of the groups. These results indicate that vitamin E may play the role of the main scavenger in the situation of a smaller dose of lipid peroxides, but when larger doses are administered, GSH-Px may play the main role as the scavenger in this experimental system.


[Relationship between autoimmune diseases and pneumoconiosis]. In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future.


[Epidemiologic study on physical conditions related to work among the elderly]. The present study was conducted in order to examine the epidemiologic factors related to work capacity among the elderly. As study area, Ogimi Village in Okinawa Prefecture was selected by reason of the long life expectancy of the inhabitants. Medical examination and interview were conducted on 756 inhabitants aged 65 yr and older. Working status was classified into two groups, that is, working group and non-working group. The association between working status and related factors was examined by using multiple logistic regression analysis. The examined factors were as follows: sex, age, history of apoplexy, history of being down, history of falls, history of fracture, chewing ability, pain, exercise habit, hobby, education, number of family members, alcohol, smoking, food intake frequencies and medical indicators (blood pressure, ECG, Quetlet index, skinfold thickness, grip strength, one-leg test with eyes opened, albumin, total cholesterol, hemoglobin and HDL-cholesterol). The results of the analysis revealed that grip strength and one-leg test with eyes opened had a statistically significant correlation with working status (p < 0.01). From the results, maintenance of muscle strength and equilibrium function were found to be the physical conditions related to work among the elderly in the agricultural area.


[Effect of hydrolysis conditions on the determination of urinary 2,5-hexanedione in workers exposed or not exposed to N-hexane]. In order to determine the optimal conditions of acid hydrolysis for urinary 2,5-hexanedione (HD) measurement, the effects of urine pH or volume of HCl added to urine and hydrolysis period were studied using gas chromatography-mass spectrometry (GC-MS). When 0.3 ml of concentrated HCl was added to 3 ml of urine, complete hydrolysis to liberate HD was attained 2 h after the start of heating at 100 degrees C for urine from non-exposed subjects. On the contrary, in urine from exposed subjects most of HD was liberated in 30 min at 100 degrees C, suggesting that the urinary substrates converted to HD by acid hydrolysis were different between exposed and non-exposed subjects. It was confirmed that hydrolysis for 2 h at 100 degrees C with 0.3 ml of concentrated HCl added to 3 ml of urine gave the most reliable levels and the greatest amounts of HD in both urine from exposed and non-exposed subjects. Reference values were determined by the hydrolysis conditions presented here. In 84 males, 52 females, and 136 with sexes combined the urinary HD levels were 0.35, 0.49, and 0.39 mg/l (geometric mean), respectively. Urinary HD levels determined without hydrolysis (free HD) were less than 0.006 mg/l in 31 control subjects examined. In urine from exposed subjects the amount of free HD was about one-fifth of the total HD (free plus conjugated HD) as determined with acid hydrolysates, although the percentage of free to total HD varied from 0.4 to 28%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Utility of Mahalanobis distance in evaluating the results of health examination]. A method using Mahalanobis distance (D2), the general probability distance in multivariate analysis, was studied for evaluating the results of health examination. D2 of each subject was computed by a personal computer with a BASIC program, and those whose D2 values lay out of 95% confidence interval were considered to be abnormal. In the present study, the mean value and standard deviation come from a normal range of Japanese, and the correlation coefficients between two items were obtained from blood donors in the hospital. These three parameters were necessary for calculation of D2. To examine the availability of this method, the data of a health examination on 370 new employees from 18 to 25 yr in age were analyzed with 9 items, including systolic pressure (SBP), diastolic pressure (DBP), serum glutamic oxaloacetic transaminase activity (GOT), serum glutamic pyruvic transaminase activity (GPT), serum gamma glutamyl transpeptidase activity (GGTP), serum total cholesterol (TCHO), serum triglyceride (TG), number of erythrocytes (RBC), and concentration of hemoglobin (Hb). It was shown that the data distributions of GOT, GPT, GGTP, and TG were log normal, and those of the other items were normal. With this method, 39 persons were also judged as abnormal from 46 subjects diagnosed to be abnormal by doctors, and the remaining 7 were missed but could be classed to be normal, as six of them had only slightly high levels of GPT (33-39 IU/l) and/or GGTP (42-57 IU/l), and one had a slightly high SBP (146 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)


[Sex difference of free erythrocyte protoporphyrin (FEP) level. III. Effect of estradiol on porphyrin metabolism, especially in FEP, in lead poisoned rats]. An experimental study of sex hormone on FEP level in rats was conducted to clarify sex difference of FEP level. A total of 42 male Donryu rats were divided into 7 groups; group I (control 1; olive oil injection without castration), group II (control 2; olive oil alone), group III (EL; estradiol in olive oil, 50 micrograms/kg.BW), group IV (EH; estradiol in olive oil, 250 micrograms/kg.BW), group II' (Pb; Pb 5 mg/kg.BW), group III' (PbEL; Pb 5 mg/kg.BW + estradiol in olive oil, 50 micrograms/kg.BW) and group IV' (PbEH; Pb 5 mg/kg.BW+estradiol in olive oil, 250 micrograms/kg.BW). Excluding group I, all rats of the 6 groups were castrated. After one week from castration, estradiol was subcutaneously injected 4 times a week, and lead was intraperitoneally injected once a week for 6 wk. Estradiol suppressed growth, Ht, Hb value and liver function, but did not show any evident effect on FEP, ALA-U and CP-U. Erythrocyte ALA-D activity in group IV' (Pb+estradiol at high dose) showed a level higher than that in group II' (Pb-treatment alone).


[Replacement of fluid lost due to sweating in a hot working-environment]. Replacement of fluid lost due to sweating in a hot working-environment was determined by measuring the body weight of 14 workers (53.6 +/- 7.1 years old) 5 times during a working day. They were engaged in repairing and/or maintaining blast furnaces in an environment of 27.9-42.6 degrees C in WBGT. The amount of fluid consumption from a free intake of either green tea and tap water or green tea, tap water and glucose-electrolyte solution (Pocari, Otsuka Pharmaceutical Co., referred to as G-E solution) was compared. The body weight loss during work was 1.70 +/- 0.70 kg when free intake of fluids plus G-E solution was allowed, while it was 1.60 +/- 0.65 kg when G-E solution was not allowed. Fluid intake with G-E solution was 1.03 +/- 0.35 l, and they could rehydrate 61%. Without the G-E solution fluid, was 0.75 +/- 0.37 l (47% rehydration). Fluid intake with G-E solution was significantly (p < 0.05) larger than that without it. The body weight difference between pre -ad post-work was significant (p < 0.001), i.e., it was 0.26 +/- 0.52 kg while drinking G-E solution and 0.52 +/- 0.53 kg without it. These results suggest that restoration of body fluid after thermal dehydration takes place much faster when consuming G-E solution.


A sandwich enzyme immunoassay for liver-specific antigen and its forensic evaluation. We attempted to develop a method for the determination of liver injuries, using a liver-specific antigen as a marker. The liver-specific antigen (LSA) was purified from the human liver and the antibody to the human LSA only reacted with the liver extract using the immuno-dot-blotting technique. Depending on the immunohistochemical study, the LSA was found to be located within the cytoplasm of hepatocytes. A sensitive and specific sandwich enzyme immunoassay was then developed for the measurement of LSA. The detection limit of human LSA was 1 fmol/tube (52 pg/tube) and this assay was not affected by hemolysis. The LSA levels in serum and blood from healthy subjects were distributed within a range below the detection limit. The LSA levels in the blood from cadavers whose livers had been damaged, were markedly elevated in comparison with the normal levels found in other cadavers (10-140 fold). No cross-reaction was observed with the liver extracts from several species (mouse, rat, guinea pig and rabbit). These results suggest that the measurement of LSA levels in blood will become a useful marker for the detection of liver injury.


Further study of human salivary alpha-amylase polymorphism. Genetic variants of salivary alpha-amylase were studied using isoelectric focusing in a pH gradient of 6-8 and silver staining methods. Five phenotypes which were tentatively named Amy1 N, Amy1 SN, Amy1 V1N, Amy1 V2SN and Amy1 V3N were detected. The phenotype frequencies in 371 unrelated Japanese were: Amy1 N = 94.33, Amy1 SN = 2.43, Amy1 V1N = 0.54, Amy1 V2SN = 0.27 and Amy1 V3N = 2.43%, respectively. Although variant bands of Amy1 V1N were detected by immunoblotting method using anti-human salivary amylase, those bands were not stained by starch-iodine method for the detection of amylase activity. This suggested that a mutation was occurred in the region of amylase molecule which showed the activity. Amy1 V2SN comprised the production of three Amy1 genes and indicated the duplication of Amy1 gene. The individuals showing Amy1 V3N phenotype accorded with those showing amylase variant by PAGE.


Beta-endorphin secretion at the time of sudden death due to cardiac or respiratory failure. Using male and female Wistar rats, pituitary response to cardiac and respiratory failure type (CFT and RFT) sudden death caused by the intravenous administration of KC1 and SCC, respectively, was examined by analyzing variation in pituitary immunoreactive beta-endorphin (IR-beta-EP) levels determined by radioimmunoassay after death and in circulating IR-beta-EP levels during periods of agony. In the pituitary gland of both sexes which differed significantly in ratio of the organ weight to body weight for CFT and RFT (CFT greater than RFT), IR-beta-EP was significantly less in RFT than in CFT (p less than 0.05). No variation in plasma IR-beta-EP was noted during short periods of agony in CFT, but it markedly increased during long periods of agony in RFT. The highest elevation at 2 or 4 minutes after SCC administration was about 3 times the preadministration value for IR-beta-EP in males (p less than 0.01). But elevation in females was lower than in males. Rise plasma IR-beta-EP during agony of RFT is regarded to be of pituitary origin due to dexamethasone treatment. The pituitary was thus concluded to respond more to the fatal agony in RFT than in CFT.


[Potentiation by carbon dioxide of carbon monoxide-induced death in the hypoxic condition]. This study was aimed at clarifying the effect of carbon dioxide (CO2) on the toxicity of carbon monoxide (CO) in the hypoxic condition. In order to evaluate the coexistent toxicity of CO2 and CO under hypoxic hypoxia, we investigated the difference of CO toxicity between under the hypoxic and hypercapnic hypoxia in point of lethality in conscious male mice. Furthermore, we measured blood gases (pO2 and pCO2), pH, COHb concentration, and blood pressure (BP) and heart rate (HR) in urethane anesthetized male rabbits inhaled with 2 toxic gases: N2-toxic gas (O2 5.0%, CO 1.8%, N2 93.2%) and CO2-toxic gas (O2 5.0%, CO2 16.0%, CO 1.8%, N2 77.2%). The animals were inhaled with the 2 toxic gases until the BP reached 0 or 20 mmHg. In the latter case, when the BP reached 20 mmHg, the animals were inhaled with air and were intravenously infused with saline (20 ml/kg/30 min). Conscious mouse experiment: In the both types of hypoxia, LC50 were decreased with the decrease of O2 concentration and the LC50 of CO in hypercapnic hypoxia was significantly lower than that in nitrogen-replacement hypoxia in the range of 12% and 9% of O2 concentration in male mice. BP 0 mmHg-group experiment in rabbits: All the rabbits inhaled with N2-toxic gas or CO2-toxic gas died. The time to BP 0 mmHg in CO2-toxic gas group (7.8 +/- 0.33 min) was shorter than that in N2-toxic gas group (11.5 +/- 1.00 min). Although both toxic gases lowered pO2 level and elevated COHb% of the blood, CO2-toxic gas extremely elevated pCO2 level by 80-100 mmHg corresponding to lowering the serum pH by 0.37-0.45. BP was firstly elevated during 2-3 minutes by inhalation of these toxic gases and was finally lowered to die. HR decreased continuously after the inhalation of toxic gases until the animals died. BP 20 mmHg-group experiment in rabbits:Recoveries of COHb%, pCO2 level and pH of the blood in N2-toxic gas intoxication were significantly faster than those in CO2-toxic gas group. The times to COHb 10% were 64.2 min and 78.2 min in N2-toxic gas and CO2-toxic gas, respectively. But, there was no significant difference between N2-toxic gas and CO2-toxic gas intoxications in the recoveries of pO2 level, BP and HR. The above results suggest that CO2 potentiates the CO-intoxication under hypoxic hypoxia and our methods of coexistent gas toxicity may be useful for examining the gas toxicity in fire accident.


[Trace analysis for drugs and poisons in human tissues]. Despite continuous developments of analytical techniques in terms of sensitivity and accuracy, uncountable increase in number of chemical substances are brought into the field of forensic sciences to be analyzed. Based on the idea that progress in analytical technique to cope with the change of situation is always required, a research team including 10 members was organized to set up the most advanced methods at present to analyze the important drugs and poisons in biological materials for forensic purposes. Stimulant drugs such as methamphetamine and amphetamine were studied on the improvement of extraction procedure prior to mass spectrometric analysis. A conventional solvent extraction method was replaced by an extraction technique using Extrelut column. The technical procedure was simplified and the accuracy of measurement was improved. The changes in CO-Hb concentration in the whole blood in storage was examined with regard to the lapse of time and temperature, where a differential spectrophotometry was used. Useful information could be obtained from practical aspects. Analytical conditions of gas chromatography were revised on volatiles including alcohols, especially as to column conditions. The use of capillary column was recommended for sensitivity and peak separation. The optimum conditions for detecting barbiturates in the blood were examined. The combination of Sep-pak C18 cartridge with a capillary column for gas chromatography using nitrogen phosphorus detection was found preferable. Mass spectrometry of various kinds of local anesthetics was studied. Quantitative analysis of the drugs was examined on gas chromatography with a surface ionization detector. Three types of insecticides including organophosphorus, chlorinated and fluorine compounds were analyzed by gas chromatography/mass spectrometry in order to establish a sensitive and selective method. The detection limits, calibration and reproducibility were examined. Herbicide, paraquat, was examined on the sensitivity, recovery, required time and costs in connection with methods of pretreatment and analytical procedure. A secondary spectrophotometry was found useful practically. Antimony in biological tissues was analyzed, using a flameless atomic absorption spectrometer with carbon tube atomizer. The time for analysis was reduced, and sensitivity was improved. Immunoassay method was examined from general aspects on drugs and hormones. Using antibodies specific to haptens, the dynamics of such antigens as drugs and hormones in the body tissues were observed. Interfering substances at the time of toxicological analysis were checked in order to obtain reliable information. Exact identification was found possible by using gas chromatography/mass spectrometry. As described above, the research was made from the practical aspects of forensic toxicology, and meaningful results could be obtained from each study.


[Reports on medico-legal data from massive investigation performed by the Medico-Legal Society of Japan--weight and size of internal organs of normal Japanese today]. A statistical study was made on the weight and size of internal organs of normal Japanese. The most of them were judicially autopsied by forensic pathologists all over Japan up to 1989. In these materials, the following cases were excluded; cases with long postmortem intervals, with diseases or damages to many organs, receiving therapeutic transfusion or infusion and cases of death by fire. In every case, the data was neglected when the organ itself had abnormality or damage, but the data from other organs were included. Thus, the total number of cases was 5,144, comprising 3,322 males and 1,822 females. The materials used are as follows; sudden natural death 941 cases (18.4%), death due to wound(s) 2,476 cases (48.4%), asphyxia 1,261 cases (24.7%), poisoning 257 cases (5.0%), death from cold 68 cases (1.3%), death due to burns 46 cases (0.9%) and others 62 cases (1.2%). The results obtained are presented in Table 1-12.


Analysis of glycated albumin in postmortem blood samples as the diagnostic parameters of diabetes mellitus. Glycated hemoglobin (GHb), fructosamine and glycated albumin (GA) in hemolytic sera from cadavers were analyzed for the postmortem diagnosis of diabetes mellitus. The levels of GHb and fructosamine were determined by boronate affinity chromatography and colorimetry, respectively. Albumin fraction was isolated from the samples by Affi-Gel Blue affinity chromatography. The glycated and non-glycated molecules were separated by boronate affinity chromatography, and quantitated by bromcresol green method. Fructosamine could not be analyzed from highly hemolytic sera containing more than 10 g/l hemoglobin. In such samples, the levels of GHb and GA were deviated from the standard values, indicating their postmortem degradation. In less hemolytic samples, GA was as informative as GHb and fructosamine for the diagnosis of diabetes mellitus.


[Identification of optical isomers of methamphetamine and its application to forensic medicine]. In order to identify optical isomers (d and l-) of methamphetamine (MAMP), GC-MS analysis using optically resolvable reagent of N-trifluoroacetyl-L-prolyl chloride (L-TPC) and HPLC analysis using chiral cellulose-based columns were compared. In analysis of d- or l-MAMP (M) of TPC (T) derivatives by the GC-MS, contrary to the expectation that only d(M)-L(T) or l(M)-L(T) could be detected chemically, two diastereomers of d(M)-L(T) and d(M)-D(T) for d-MAMP and two of l(M)-L(T) and l(M)-D(T) for l-MAMP were demonstrated respectively. This results was attributed to a small percentage of D-TPC present in L-TPC. For racemic (dl)-MAMP, none of these four isomers could be individually isolated, and they were detected as two overlapping peaks. In the HPLC analysis using chiral columns, d- and l-isomers of MAMP and amphetamine (AMP) could be clearly isolated with merely one analytical procedure, and the l/d ratio was possible to calculate with facility. From the rats urine administered d- or l-MAMP, only the corresponded optically active form of the administered drug was detected, and when racemic (dl)-MAMP was administered, d-MAMP, l-MAMP and their metabolites AMP were distinctly detected. The l/d ratio calculated from amount of MAMP and AMP excreted in rat urine within 24 hr was not in accordance with that of the administered dl-MAMP (l/d = 1.01): the l/d ratio was 0.45 for MAMP and 0.58 for AMP, and 0.50 for the total of MAMP and AMP. The similar results were observed in case of racemic (dl)-AMP. From several human specimens obtained from the cadavers dead by MAMP poisoning, only d-MAMP and the metabolite d-AMP were detected, and neither l-MAMP or l-AMP were demonstrated. In particular, a high concentration of d-MAMP was detected in gastric contents, brain, lung and liver. From the MAMP powder in possession, only d-MAMP was detected. These results suggest that this chiral column-HPLC procedure could be applied to medicolegal practice and forensic scientific investigation.


[Investigation of algorithm for the calculation of probability of paternity likelihood using personal computer program, including the application to parentage testing in the decreased party]. Algorithm for the computerized calculation of probability of paternity likelihood was investigated. The probability is calculated by Essen-Möller's formula as W = X/(X+Y) = 1/(1 + Y/X). The X value is also given as X = Hl, m, n/Kl, m, where kl, m and Hl, m, n are the probabilities of mother-child and mother-child-father combinations, respectively. In this study, four functions as F(PQ) = [1-(P not equal to Q)] x p x q, Z(RS) = (1- (R = S)), K(PQ,RS) = 1/2([(R = P) + (R = Q)].s + [(S = P) + (S = Q)].r).F (PQ)/Z(RS) and H(PQ, RS, TU) = 1/4([(R = P) + (R = Q)] [(S = T) + (S = U)] + [(S = P) + (S = Q)] [(R = T) + (R = U)]) x F(PQ).F(TU)/Z(RS) were created, where PQ, RS and TU were the genotypes of mother, child and the alleged father, P, Q, R, S, T and U were their alleles, and p, q, r, s, t and u were the allele frequencies. The equality or inequality in parenthesis was the relation operator which gave -1 or 0 when the expression was true of false, respectively. Then, three formulae as Y = n sigma k = l F([TU]k), Kl, m = 1 sigma i = l m sigma j = l K ([PQ]i, [RS]j) and Hl, m, n = l sigma i = l m sigma j = l n sigma k = l H([PQ]i, [RS]j, [TU]k) were obtained, where [PQ]i, [RS]j and [TU]k were one of the mother's, one of the child's and one of the putative father's genotypes considered from their phenotypes, respectively. Using these formulae, the probability of paternity likelihood could be calculated in every case. These formulae were programmed in BASIC language using a personal computer. Algorithm for the calculation of the probability in the deceased party was also investigated.


[Three cases of acute methamphetamine intoxication--analysis of optically active methamphetamine]. Three typical cases of acute methamphetamine intoxication are reported. The concentrations of methamphetamine in the blood were 27.2, 6.43 and 0.60 micrograms/ml, respectively. All three victims had been exposed to high temperature in a bathroom or a closed room in summer at the time of death. Macroscopic autopsy revealed hemorrhagic pulmonary edema, and histologically, diffuse contraction-band necrosis was evident in the myocardium in all cases. The absolute structures of six illegally available methamphetamine showed an (S)-configuration with an optical purity of > 99% in enantiomeric excess and four were racemic form.


[Analysis of thinner components using the Curie-point pyrolyzer-gas chromatographic method in the tissues of a victim fatally poisoned]. A 43-year-old male was found dead in the trunk of his car which was filled with thinner vapor. Thinner components in the tissues were analyzed using a gas chromatograph equipped with Curie-point pyrolyzer (Py-GC), and a gas chromatograph-mass spectrometer. The Py-GC method was able to analyze with very small materials. It was simple and quick but not as sensitive as the head-space gas chromatographic method. Toluene, ethylbenzene and xylenes were detected in the tissues, and their presence was confirmed by gas chromatography-mass spectrometry. The concentrations of toluene, ethylbenzene and xylenes in blood and the brain were 56.8, 6.8 and 4.5 micrograms/ml; and 203, 43.5 and 33.9 micrograms/g, respectively. The cause of death was thus judged as be thinner poisoning.


[A fatal case caused by organophosphorus insecticide intoxication and confirmed by the metabolite found in the blood]. An 83-year-old woman and two other members of her family were poisoned after eating lettuce prepared with Ethimethon Granule 6 instead of salt by mistake. Ethimethon Granule 6 is a mixture of organophosphorus pesticides, disulfoton and diazinon. All three were admitted to a hospital, and she died 22 h after ingestion and the others recovered. Disulfoton and diazinon in the remaining lettuce were detected and confirmed by gas chromatography-mass spectrometry. The pesticides, however, were not detected in the blood sample collected from the victim at autopsy. A metabolite of disulfoton, phosphorothiolate sulfone, was detected by FPD-gas chromatography, and confirmed by gas chromatography-mass spectrometry.


[A case of suicide by an intravenous injection of pancuronium]. A 25-year-old male anesthesiologist was found dead in his room with an intravenous drip line connected with his leg. There were several empty ampules of pancuronium, midazolam and buprenorphine around him. Pancuronium and midazolam in the blood and urine samples collected at postmortem examination were detected by spectrofluorometry and ECD-gas chromatography, respectively. The concentrations of pancuronium and midazolam were 0.3 micrograms/g and 0.12 micrograms/g in the blood, respectively; 0.9 micrograms/g and 0.05 micrograms/g in the urine, respectively. The cause of death was determined to be asphyxia due to respiratory muscle paralysis caused by pancuronium.


Inhibitory reflex during bronchoconstrictions induced by histamine and Ascaris suum antigen. We investigated the involvements of sympathetic and nonadrenergic nervous systems in the inhibitory reflex following bronchoconstriction in dogs. Inhalations of a 0.00125% solution of histamine and Ascaris suum antigen (3 mg protein) to the bronchial side induced reflex tracheal constriction following bronchoconstriction. An intra-arterial infusion of 5 micrograms/min of atropine to the tracheal site changed the reflex tracheal constrictions by histamine and antigen inhalations into tracheal dilatations. The reflex tracheal dilatations were abolished by the combination of intra-arterial propranolol (100 micrograms) and transections of both the bilateral superior laryngeal nerves and the spinal cord at the C1 level. The reflex tracheal constrictions induced by histamine and antigen inhalations were increased with 100 micrograms propranolol. Furthermore, the reflex tracheal constrictions were enhanced by the combination of 100 micrograms propranolol and transection of the spinal cord. These findings indicate that during the constriction of the bronchial smooth muscle, not only a reflex tracheal constriction mechanism but also one of reflex dilatation operates and that the latter reflex response may be mainly mediated by the sympathetic nerves, with partial involvement of the nonadrenergic nerves. This inhibitory reflex may attenuate asthmatic bronchoconstriction.


Peptide leukotriene antagonistic activity of AS-35, a new antiallergic drug. The effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (AS-35), a newly synthesized compound, on leukotrienes (LTs) antagonistic activities were investigated in vitro and in vivo. In isolated guinea pig preparations, AS-35 antagonized LTC4-, LTD4- and LTE4-induced contractions of the ileum with IC50 values of 8 nM, 4 nM and 3 nM, respectively. In the trachea, the agent also antagonized LTD4- and LTE4-induced contractions with IC50 values of 10 nM and 20 nM, respectively. However, LTC4-induced tracheal contraction in the presence of L-serine borate was not antagonized by AS-35. Histamine-, acetylcholine-, serotonin- and bradykinin-induced contractions of the ileum, carbachol-, prostaglandin D2-, prostaglandin F2 alpha-induced contractions of the trachea and LTB4-induced chemotaxis of rat polymorphonuclear leukocytes were not inhibited by AS-35. As to the in vivo models, AS-35 (i.v.) dose-dependently antagonized bronchoconstriction induced by i.v.-injection of LTC4 and LTD4 in anesthetized guinea pigs, but did not inhibit histamine-induced bronchoconstriction. Oral administration of AS-35 also antagonized LTD4- as well as antigen-induced LT-mediated bronchoconstriction. In addition, LTD4-induced increase in the cutaneous vascular permeability of guinea pig was inhibited by the drug (p.o.). These results indicate that AS-35 is an orally effective, potent and selective peptide LT antagonist.


Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. The inhibitory effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (AS-35), a peptide leukotriene (LT) antagonist, on specific bindings of radiolabeled LTC4 and LTD4 in guinea pig lung membrane were investigated to clarify the mechanism by which this agent inhibited LT-induced physiological responses. Binding assays were performed at 20 degrees C in 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM CaCl2, 10 mM MgCl2 and 10 mM cysteine in the absence (LTD4 binding assay) or presence (LTC4 binding assay) of 80 mM L-serine borate. Scatchard analysis of each LT specific binding indicated a single and high affinity binding site with a Kd of 0.21 +/- 0.05 nM and Bmax of 808 +/- 71 fmol/mg protein for [3H]-LTD4, and with a Kd of 21.6 +/- 3.8 nM and Bmax of 74.9 +/- 2.6 pmol/mg protein for [3H]-LTC4. Competition binding studies showed that AS-35 antagonized [3H]-LTD4 specific binding with a Ki value of 92.7 nM. In contrast, AS-35 was 100 times less effective in inhibiting [3H]-LTC4 specific binding, compared with [3H]-LTD4 specific binding. These results indicate that AS-35 interacts directly with peptide LTs receptors, especially the LTD4 specific binding site to produce its pharmacological effects.


Improvement of drug-induced cardiac failure by NKH477, a novel forskolin derivative, in the dog heart-lung preparation. The efficacy of NKH477, a novel water-soluble forskolin derivative, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital, propranolol or verapamil so that cardiac output had been reduced by about 40-50% of the respective control were all improved by NKH477 (10-100 micrograms) in a dose-dependent manner. With 100 micrograms NKH477, almost complete restoration of cardiac performance was attained in the respective cardiac failures. In the combination of NKH477 with ouabain (30 micrograms), 30 micrograms of NKH477 completely restored the cardiac function depressed by pentobarbital, associated with a slight but not significant increase in heart rate. No arrhythmias were induced by any of the NKH477 doses used in the experiments. These results suggest that NKH477 should be subjected to clinical trials in the treatment of cardiac failure.


The contraction mechanisms for norepinephrine in single cells prepared from tracheal smooth muscles of guinea pig of different ages. Single cells were prepared from guinea pig tracheal smooth muscle and used in an experiment on the contraction mechanisms for norepinephrine and a study on the change of alpha 2-adrenoceptors with age. Specific bindings of [3H]p-aminoclonidine to the single cells from the tracheal smooth muscles of 6- and 40-week-old guinea pigs were saturable and analyzed by Scatchard plot. The maximum number of [3H]p-aminoclonidine binding sites was larger in the preparation from 40-week-old guinea pigs than that from 6-week-old animals, while its dissociation constant did not change with age. The amount of prostaglandin F2 alpha released from the single cells was increased by norepinephrine, not affected by phenylephrine, and reduced by an alpha 2-antagonist such as yohimbine. The amount released by norepinephrine was significantly larger in the preparation from 6-week-old guinea pigs than that from 40-week-old animals. These results suggest that the age-related decrease in the potency of norepinephrine is due to reduction in the amount of excitable prostaglandin F2 alpha released by the drug, but not to a change in the total amount of alpha 2-adrenoceptors or the dissociation constant of the drug with respect to these adrenoceptors. Furthermore, alpha 2-adrenoceptors in the tracheal smooth muscle cell play an important role in the release of prostaglandin F2 alpha and the production of contractile responses of these muscles.


Inhibition of gastric glucosamine synthetase activity by oxygen radicals: a possible cause of decreased mucosal protective capacity. To clarify the role of oxygen radicals in the mucus metabolism of the gastrointestinal tract, the effect of oxygen radicals on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, was investigated using homogenate derived from rat gastric mucosa. The simultaneous addition of both xanthine and xanthine oxidase caused a significant inhibition of the enzyme activity, and this decrease was counteracted by catalase, but not by superoxide dismutase. Hydrogen peroxide also caused a significant decrease in the enzyme activity; and this effect of hydrogen peroxide was counteracted by catalase and dithiothreitol, but not by mannitol, dimethyl sulfoxide and reduced glutathione. The inhibition of glucosamine synthetase activity by oxygen radicals is considered to be caused by the oxidation of sulfhydryl groups of the enzyme molecule. The present results also suggest that oxygen radicals in the gastrointestinal tract may induce the suppression of a protective mechanism of the gastric mucosa by inhibiting glucosamine synthesis activity.


Neurochemical investigation on the effects of a new diphenylpiperazine calcium antagonist, KB-2796, on the central dopaminergic system of rats. The effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the striatal dopaminergic system of rats were investigated in comparison with various calcium antagonists and the dopamine antagonist chlorpromazine. The inhibiting effect of KB-2796 on [3H]spiperone binding to striatal membranes in vitro was weaker than those of chlorpromazine and the other diphenylpiperazine analogues, flunarizine and cinnarizine, and more potent than those of verapamil and nicardipine. Diltiazem and nifedipine were inactive. KB-2796 (30, 100 mg/kg, p.o.) had no effect on Kd and Bmax values of in vitro [3H]spiperone specific binding to striatal membranes obtained from the rat at 36 hr and 7 days after repeated administration for 18 days, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased Bmax values by 47% and 31%, respectively, at 36 hr, but not at 7 days after the final administration. At 1 hr after the single administration, KB-2796 (30, 100 mg/kg, p.o.) had no effect on the content of dopamine and its metabolites in the striatum, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased the level of homovanillic acid. These results indicate that flunarizine may affect dopaminergic neurotransmission by partially blocking dopamine D2 receptors, while KB-2796 has negligible in vivo effect on the dopaminergic system.


Different pathways for Ca2+ influx and intracellular release of Ca2+ mediated by muscarinic receptors in ileal longitudinal smooth muscle. Muscarinic receptor-mediated elevations in intracellular Ca2+ concentration ([Ca2+]i) in the longitudinal smooth muscle of guinea pig ileum were studied by the use of fura-2 fluorescence. Dose-response analysis indicated a difference in the potencies of carbachol (CCh) to increase [Ca2+]i in the presence and absence of extracellular Ca2+. For the increase in [Ca2+]i due to Ca2+ release from intracellular stores in the absence of extracellular Ca2+, the ED50 value of CCh was 3 x 10(-5) M. On the other hand, in the presence of Ca2+, the ED50 value was 2.5 x 10(-7) M, indicating that a low concentration of CCh (less than 10(-7) M) caused influx of extracellular Ca2+ without Ca2+ release. Oxotremorine and pilocarpine induced Ca2+ influx, but were less potent inducers of Ca2+ release. CCh also stimulated the formation of inositol trisphosphates (IP3) with an ED50 value of (4.5 x 10(-5) M), which was similar to that for Ca2+ release from intracellular stores. Treatment of the smooth muscle with neomycin (1 mM), a phospholipase C inhibitor, abolished both CCh-induced IP3 formation and Ca2+ release from intracellular stores, but did not affect CCh-induced Ca2+ influx. These results suggest that the pathway for muscarinic stimulation of Ca2+ influx through plasma membranes is different from that for Ca2+ release from intracellular stores, which seems to be coupled with IP3 formation.


Effect of Ca2+ antagonists on high-K+ evoked increase in [Ca2+]i in rat cerebral synaptosomes and hippocampal neurons. By fura-2 fluorometry, we investigated the direct effects of Ca2+ antagonists including a new benzothiazepine, clentiazem, on the high-K(+)-evoked increase in the concentration of cytosolic free Ca2+ ([Ca2+]i) in rat cerebral synaptosomes and cultured hippocampal neurons. In both preparations, metal ions inhibited the high-K(+)-induced increase in [Ca2+]i, in the following order: La3+ greater than Cd2+ much greater than Ni2+. Although flunarizine and nicardipine inhibited the K(+)-induced increase in [Ca2+]i in synaptosomes, other Ca2+ antagonists, including clentiazem and nitrendipine, had little effect at 10 microM. In hippocampal neurons, clentiazem inhibited the K(+)-induced increase in [Ca2+]i at 10 microM, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes.


Circadian rhythm of plasma uric acid and handling stress-induced hyperuricemia in conscious cebus monkeys. An apparent circadian rhythm of plasma uric acid and the effect of handling stress on plasma uric acid level in conscious cebus monkeys were demonstrated. The lowest level of plasma uric acid in the circadian rhythm occurred early in the morning and the highest, before bedtime at night. With experimental handling stress, the plasma uric acid level rose to much more than the maximum level of the circadian rhythm. Stress-induced hyperuricemia could be inhibited without an increase of urinary uric acid excretion by the minor tranquilizer diazepam at doses of more than 1 mg/kg, p.o. On the other hand, benzbromarone at 20 mg/kg, p.o. significantly inhibited the hyperuricemia with a hyperuricosuric effect, while probenecid at 50 mg/kg, p.o. had no effect on either the increased plasma uric acid or urinary uric acid excretion. Accordingly, it is concluded that the plasma uric acid level in conscious cebus monkeys easily fluctuates with experimental conditions and that the animals can be utilized to evaluate the hypouricemic and hyperuricosuric property of benzbromarone-like agents.


The effect of nilvadipine, a dihydropyridine type calcium channel blocker, on local cerebral blood flow in rats. The effect of nilvadipine, a dihydropyridine type calcium channel blocker, on local cerebral blood flow (lCBF) was investigated using the autoradiographic iodo[14C]antipyrine technique in rats. In control rats, lCBF in cortical areas and in the superior colliculus and inferior colliculus was higher than that in the hippocampus, septal nucleus, globus pallidus and substantia nigra. Nilvadipine (32 micrograms/kg, i.v.) increased lCBF in all structures (significantly in 11 of 21 structures) in spite of a 33% reduction in mean arterial blood pressure. These results confirm that nilvadipine has the ability to increase cerebral blood flow.


Influence of adrenalectomy on chronopharmacological phenomenon of furosemide in rats. The role of adrenal corticoids in the time-dependent changes in the effects of furosemide was examined. Furosemide (30 mg/kg) was given orally to adrenalectomized or sham-operated rats at 12 a.m. or 12 p.m. Urine volume and urinary excretion of sodium and furosemide for 8 hr were significantly greater at 12 a.m. than at 12 p.m. in the sham-operated rats. However, such time-dependent changes in these parameters disappeared in the adrenalectomized animals. These findings indicate that adrenal corticoids are directly or indirectly involved in this event.


[The influence of significant others on the formation of own self-image]. This study aims to verify how other persons influential for the formation of own self-image change during the period from pre-adolescence to early adolescence, and what sorts of dynamism operating among the self-image, self-image assumed by others (reflected self-image: RS), and the images of others (objective self-image: O). A SCT questionnaire was administered to altogether 370 students of both sexes in 4th, 5th and 6th grades and freshman and sophomore year of junior high school. The significant others were identified on the bases of similarity between individual own self-image and ones assumed by others. All descriptions were classified as positive, negative or other, and the inter-relationships among them were examined. Findings were as follows: 1) Though the significant others in this period did not necessarily shift from their parents to chums, males were most susceptive to others' influence in the 6th grade, while females seemed to have already established their own self-images insusceptive to others by this age. 2) The significance of chums was confirmed for males throughout their school years. For females, however, no such trend was found, suggesting that any particular significant person would either appear in a later year or never be identified.


[The effects of individual differences on self-evaluation maintenance model]. This study was conducted to examine the effects of individual differences in affiliation motivation, achievement motivation, and self-esteem on the self-evaluation maintenance (SEM) model proposed by Tesser et al. (1984). One hundred and seventy college students answered a questionnaire for measuring affiliation motivation, achievement motivation, and self-esteem, and also assessed their own as well as their friends' academic achievements in their senior high school subjects with both high and low degrees of relevancy. For those who were high in affiliative motivation, a significantly greater difference between the own and the friends' achievements was found in the academic subjects with low rather than high relevancy. However, the same difference was also greater in the academic subjects with low rather than high relevancy for those who were low in their achievement motivation or self-esteem. These results suggest that individual differences in some variables such as affiliation motivation, achievement motivation, and self-esteem would play an important role in the SEM model.


[The effects of fear on individual and group escape in a computer simulated maze]. The purpose is to compare the effects of fear on escape behavior of individual and group conditions, in a computer-simulated maze. CRT display did not provide a bird's eye view of the maze, to the subjects, but only cues, what they would see, if they were actually inside of the maze. In the group escape condition, bodies and behaviors of other people were also shown in the maze. Subjects often got too close each other and collided with each other. Fear increased the time and locomotion required to reach the exit, because of the occurrence of a "traffic jam" in the group escape condition, however, fear reduced time in the individual escape condition. In addition, fear influenced types of escape behavior, depending on the form of maze.


[Structure and functions of self-recognition need in adolescent women]. The purpose is to propose a construct of self-recognition need, and to elucidate structure and functions of the need in adolescent women. First, 242 female subjects (average age 19.0) responded to a questionnaire. The results were factor analyzed to construct two scales of the need: self-recognition need scale and escape from negative information need. Inquiring these scales and their relation with maladjustment in daily life, the higher the maladjustment, the stronger their self-recognition need. In the second survey, 236 female subjects (average age 18.9) responded, (1) subjects with stronger self-recognition approached positively to many information seeking (even when they expect negative information about themselves), (2) self-recognition need showed positive correlation with motivation for praise acquisition and rejection avoidance. The implication of these results were discussed.


[The effects of meaning information on heart rate, respiration, frontalis EMG, and peripheral temperature during imagery]. The present study investigated the effects of meaning information on psychophysiological responses during imagery. Eighteen undergraduates were divided into arousal and relaxation groups, which were then given arousal-meaning- and relaxation-meaning-oriented trainings, respectively. After the training, the subjects were given the imagery test, and inter-heartbeat-interval (IBI), respiration, frontalis EMG, and peripheral temperature during neutral, snake, and social imageries were analyzed. The results showed that there was a significant main effect in IBI for groups: the arousal group demonstrated greater IBI changes than the relaxation group. Regarding EMG, significant increases were present during snake and social imageries in the arousal group, whereas no significant increase was observed in the relaxation group. No significant difference between groups was found in respiration and temperature. The results suggest that there are some situations that accompany their primary meanings, and that meaning-oriented trainings can modify the structure of the response propositions.


[The effects of role playing on prosocial behavior in preschool children]. The purpose was to examine the effects of two types of role-playing experience on prosocial behavior in preschool children. Subjects were 72 6-year-olds. In the Empathy role-playing (E), each pair of children enacted alternately a victim and an eyewitness using a glove puppet, in which the emphasis was only on empathizing with the victim. In the Empathy and Helping role-playing (EH), they enacted alternately a victim and a helper, in which the emphasis was on empathizing and helping a victim. In the Control role-playing (C), they played roles alternately of a customer and a salesman in a grocery store. All children were assessed as for helping and sharing behaviors for a real victim before and after the role playing session. In the comparison between pre- and post-tests for helping behavior. All groups (C, E, EH) increased helping tendency, but only in EH group the proportion of subjects, whose attitude changed from helper to non-helper. As for sharing behavior, all three groups increased the number of sharing significantly in the post-test.


[A study of revised self-monitoring scale]. The present study attempted to construct the Japanese version of Revised Self-Monitoring Scale (Lennox & Wolfe, 1984). Factor analysis of this scale yielded two factors: 1) Sensitivity to expressive behavior of others, 2) Ability to modify self-presentation. This scale and its two factors had acceptable internal consistency: these results were almost similar with the original study. In correlational analyses with other personality measures, this scale correlated positively with both Private and Public Self-Consciousness Scale and Maudsley Personality Inventory-E Scale, but positively or negatively with some scales of Yatabe-Guilford Personality Inventory (e.g., G, S: positively. I, T: negatively.). Moreover the correlations between the two factors and the above mentioned measures provided interesting results. The availability of this scale was discussed.


[Type A personality and level of aspiration in preschool children: some basic characteristics of aspiration levels and their modifications by introducing risk-taking and competitive situations]. The purpose of this study was to investigate some characteristics of aspiration levels of Type A preschoolers. Twenty-two Type A and twenty-one Type B subjects selected from 245 preschoolers were given three tasks: ball-throwing task 1, ball-throwing task 2, and ringtoss task. After investigating some basic characteristics of aspiration levels in a standard situation (ball-throwing task 1), risk-taking (ball-throwing task 2) and competitive (ringtoss task) situations were introduced in order to study the modifications of aspiration levels. The results indicated that Type A children showed higher aspiration levels than Type B children, but that no differences of changes in aspiration levels by introducing risk-taking and competitive situations were found between the two types. These results were discussed from the view point of formation of Type A characteristics.


[Retrieval of faces from features described by eyewitnesses]. This experiment proposes a computer technique to find a witnessed one in the database of faces, from an eyewitness's feature description. The method is basically to choose the face with maximum likelihood for an eyewitness's description. The likelihood is derived from one of three models, in which the description of a features by a witness is based on either (i) judgement through all features, (ii) feature sampling with replacement, or (iii) feature sampling without replacement. Three models were assessed by free description task of facial features. these three models showed sufficient accuracy of retrieval, and the feature sampling without replacement model was superior to other two models.


[An examination of two distinct aspects of anxiety in adolescence]. This study aimed at measuring and examining two aspects of anxiety in adolescence. After reviewing previous studies, it was hypothesized that anxiety concept has a positive aspect of human growth promotion in addition to a negative aspect of growth inhibition. In Study I, 20 preparatory items for both positive and negative anxiety were administered to 817 high school students with three other scales relevant to human growth: "purpose in life", identity dimension, and self-concept. Ten positive anxiety items and 15 negative items were selected, referring to pattern of factor loadings. These two anxiety scales were validated using three reference scales and responses of 12 neurotic clients as standards, and the mutual independence of two aspects was confirmed. In Study II, the characteristics of two aspects of anxiety in adolescence were examined, using the data of 817 high school students and 379 undergraduates. It was found that the level of positive anxiety increased through high school years, reaching a peak in freshman year, while the negative anxiety remained about the same level in the same period.


[Effects of leader behavior on subordinate's upward influence tactics and relationship between subordinate and leader]. This study aimed at examining the upward influence tactics employed by subordinates toward their immediate superiors (the leader) in relation to the cohesiveness of a given group, leadership behavior on the part of the leader, and leadership behavior on the part of the group's top leader. The survey involved a sample of 120 nurses. Each nurse was asked to complete a questionnaire, which was prepared on the basis of an earlier preliminary study. The results of the group survey were as follows: (1) A nurse (the subordinate) generally gave play to the tactics of rationality and enthusiasm vis-a-vis a democratically inclined head nurse (the immediate superior); (2) coalition behavior was widely practiced in groups that were highly cohesive, while higher authority was employed vis-a-vis a democratically inclined top head nurse (the top leader); (3) the above-mentioned actions employing tactics of influence [(1) to (2)] had, in turn, an effect on the degree of response on the part of the head nurse (the leader) and on the ex post factor relationship between the two parties (nurse and head nurse).


[Self-disclosure and loneliness].

[Self-disclosure and loneliness]. This study examined the relationship between self-disclosure and loneliness. The self-disclosure questionnaire (ESDQ) and the loneliness scale (LSO, consists of two subscales, U-scale and E-scale) were administered to 114 female subjects (junior college students). Results show that self-disclosure scores were negatively related to the U-scale of loneliness (whether or not they believe in mutual sympathy among human beings), but not to the E-scale of loneliness (whether or not they are conscious of individuality of each individual). The results suggest that we have to specify the quality of loneliness in question, when we examine the relationship between self-disclosure and loneliness.


[Saccadic eye movement guided by the visual form]. This report describes an experiment in which was measured the onset latency of the saccade to the peripheral target under three conditions of visual cues for the target location. In the central cue condition (the C-condition), the cue was an arrow presented in the central visual field. In the peripheral cue condition (the P-condition), the cue was the form in which the target was presented in the peripheral visual field. In the one-sided cue condition (the O-condition), the cue was the target itself. The saccade latency was measured by means of electro-oculography. The results were; (1) the saccade latencies in the three conditions were significantly different from each other, (2) the latency was longest in the C-condition and shortest in the O-condition, (3) the difference in latency between the P and C-conditions was three times as large as that between O and P-conditions, (4) the latency variance was significantly larger in the C-condition than in the other conditions, (5) the difference in the variances was not significant between the O and P-conditions. The results were interpreted in terms of (a) cognitive processing of visual form and (b) the characteristics of the saccade system.


[Assessment of autonomic function by the spectral analysis of heart rate variability: an examination in a mirror drawing task]. The effect of an experimental task on autonomic function was investigated by spectral analysis of heart rate variability in 13 male college students. Power spectral density of heart rate variability has been said to contain two significant components: respiratory sinus arrhythmia (RSA) as an index of cardiac vagal activity, and Mayer wave related sinus arrhythmia (MWSA) as an index of sympathetic activity with vagal modulation. Those two components were examined during a task of mirror drawing on the CRT. In order to eliminate the effect of respiratory rate on RSA, the respiratory rate was controlled at 15 breaths/min. Furthermore, the coefficient of variance of R-R interval (CV-RR) and the fluctuation of plethysmograph (PTG) were calculated simultaneously. Results indicated that, while RSA decreased significantly, MWSA did not change during the task. On the other hand, neither CV-RR nor PTG showed any significant differences during the task. These findings indicated that cardiac parasympathetic activity was diminished in the mirror drawing task. The significance of spectral analysis of heart rate variability were discussed.


[Effect of interrun interval on serial pattern learning in rats]. The effect of interrun interval (IRI) on serial pattern learning was investigated in a runway. One of two serial sequences, a monotonic decreasing sequence (14-7-3-1-0 food pellets) or a nonmonotonic sequence (14-1-3-7-0), was combined factorially with a short (30 s) or a long (30 min) IRI. Following 28 acquisition trials, a short (or long) IRI was transferred to the same sequence with a long (or short) IRI. It was found that anticipation of the O-pellet developed more rapidly in the group receiving a monotonic sequence with a 30 s IRI than that with a 30 min IRI in acquisition phase. The O-pellet was not anticipated by either of the two nonmonotonic groups. Anticipation was eliminated by the increase in IRI, whereas it was developed by the decrease in IRI in the monotonic sequence. These results suggest that time-related factors such as the decay of the memory of numbers of pellets are needed for Capaldi's memory discrimination theory.


[An evaluation of the span and direction of spread of the concept "now" (Japanese ima): using both the dual scaling and factor analysis methods]. The purpose of this study was to obtain information about both the span and direction of spread of the concept "now" (Japanese ima) used in short sentences such as "I am--a student." 583 subjects were presented with 55 sentences, and were required first to rate on a 5-point scale the degree of spread of the concept used in each sentence, and then to express its span and direction in terms of seconds, minutes, ... years, decades, or centuries in both a past- and a future-orientation. The latter data were analysed using the Dual Scaling method which revealed three major solutions: "span", "direction", and "interrelation between the previous two". The former data were analysed using the Factor Analysis method which revealed six factors: "moment", "conversion", "limitlessness", "absorption", "limitation" and "hopelessness". Furthermore, second-order analyses were carried out using these six factors, revealing three further factors: "duration", "change" and "timelessness". It was concluded that these latter three factors were identical with the three solutions obtained by Dual Scaling.


[Factors related to the maintenance of social interaction among withdrawn preschool children]. It is difficult for withdrawn children to enter a play and to maintain social interaction with other children. This investigation attempted to identify whether the difficulty was due to their incorrect perception of others' responses or due to the lack of their self-confidence. Forty-five 5- and 6-years old nursery school children enrolled in six day-care classrooms served as subjects. They were divided into high middle or low groups by the degree of withdrawal, and each child was asked to play with two other same-age peers. Analyses by the observation of video recordings and the interviewing of the children revealed that the low withdrawals could perceive other children's responses more correctly than any other group, whereas there was no difference among the three groups in self-confidence. Thus, it was interpreted that those highly withdrawal children cannot skillfully enter plays with other children because they were unable to perceive other children's responses correctly. After entering a play, they also remained solitary almost all the time. The highly withdrawn children tended to keep themselves alone, while the children in low and middle degrees of withdrawal seemed to attempt to join other children even after being rejected or neglected by other children.


[Influence of affect on everyday memory: self-reference of retrieval cue]. There have been two views as to mood congruent recall: The one interprets it as an automatic process, while the other explains that it appears only when self-referent information processing is running. In this study, one experiment was conducted in order to examine these two opposing views. By false feedback of task performance, positive or negative mood had been induced in each subject, who was given two "cue" words, and asked to retrieve everyday events. The result was that mood congruent recall occurred when the word "self" was presented as a cue; but no effect of mood with neutral cues. This result supports the hypothesis that mood congruent recall is found only when self-referent information is processed. However, such effect was not evident in positive mood condition. In positive mood condition, there remains a possibility that mood congruent recall may be an automatic process. The effects of mood on memory were discussed from various viewpoints.


[The relationships between sympathetic and parasympathetic tones and cardiovascular responses during active coping]. The relationships between sympathetic and parasympathetic tones and a variety of cardiovascular measures were examined in 27 male college students subjected to an active coping, namely a reaction time task, for five minutes. The results demonstrated an enhanced sympathetic tone during the first one minute (P1), indicating the decreases of pre-ejection period (PEP), left ventricular ejection time, and electromechanical systole (QS2), and the increase of QT/QS2. The reactivities of QT/QS2 and PEP defined by mean changes in the P1 period differed in their relationship with cardiovascular responses in the last four minutes. Although the PEP reactivity was associated with the cardiac performance (stroke volume and PEP/LVET), the QT/QS2 reactivity was correlated with the mean blood pressure (MBP). The reactivities of respiratory sinus arrhythmia (RSA) were defined by the residual difference obtained by subtracting values estimated by baseline RSAs from the mean value of changes during five minutes period. Subjects with high RSA reactivity (vagal withdrawal) showed higher heart rate and MBP than those with low RSA reactivity. The results are discussed with respect to the cardiac loading factors and hemodynamics.


[Dyspnea and respiratory reflexes].

[Dyspnea and respiratory reflexes]. It has been suggested that afferents from intercostal muscles may play a role in the genesis of dyspnea. In this study, lower intercostal muscles were tapped or vibrated to induce a reflex, evoked potentials, and sensation. The tapping stimulus induced H reflex in the same muscle with a latency of 12 msec. Also the same stimulus induced evoked potentials in the cerebral cortex (N1: 19.8 +/- 1.2 msec). This suggests projection of the intercostal muscle spindle afferents to the cerebral cortex. 100 Hz vibration induced a later component, presumably an event-related potential, at 250 msec after the onset of both the inspiratory and expiratory phase. Thus, it may be possible that intercostal muscle spindle afferents project to the cerebral cortex and play a role in respiratory sensation. It has been suggested that dyspnea is reduced by increasing inspiratory and expiratory intercostal muscle spindle afferents during the inspiratory and expiratory phases, respectively. Thus, stretching the inspiratory and expiratory intercostal muscles during the respective muscular contraction phase may be effective in reducing dyspnea.


[Dyspnea sensation and chemical control of breathing]. In order to estimate the role of peripheral chemosensitivity in dyspnea sensation, we performed BH experiment under the acute or chronic hypoxic condition. The former was simulated by a given rate (0-3.2 mg/kg/hr) of doxapram infusion. The latter experiment was carried out during sojourn in Lhasa (3700 m), China. Subjects conducted BH by inhaling 7% CO2 in O2 and assessed dyspnea sensation by visual analog scale (VAS) while repeatedly measuring PCO2 at breaking point (BP). Lowering of resting PETCO2 by augmented ventilation was derived by doxapram infusion and during acclimatization at high altitude. The effect of PCO2 on VAS was enhanced by doxapram. However, altitude acclimatization resulted in attenuated effect of PCO2 on VAS despite of further development of hypocapnia. The rate of PCO2 elevation during doxapram infusion was reduced and it might be attributed to decreased body storage of CO2. On the other hand, its rate was tended to recover to sea level value after acclimatization at high altitude and it may have cancelled the mitigated dyspnea sensation. Thus, BHT almost comparable period in both acute hypoxia and during altitude acclimatization. These results suggest that CO2 storage in the body contributes to modify dyspnea sensation as well as augmented peripheral chemosensitivity.


[Dyspnea and behavioral control].

[Dyspnea and behavioral control]. Respiration is automatically regulated via chemo- and mechanoreceptors existing in and outside the lungs, but it is also controlled voluntarily by behavioral factors. Voluntary increase in ventilation accentuates dyspnea and the sensory intensity at a given ventilation does not differ from that of exercise-induced hyperventilation, but it is significantly smaller than that during hypercapnia or hypoxia. Voluntary constraint of ventilation augments dyspnea in proportion to the degree of constraint even under isocapnic hyperoxia, and the respiratory sensation during constrained breathing is qualitatively more discomfortable than that during hyperventilation. Changes in the level and pattern of breathing under constant levels of chemical stimuli increase respiratory sensations and the intensity of dyspnea is minimal near the spontaneous levels, which supports the hypothesis that breathing is behaviorally regulated in part to minimize dyspnea. The system of behavioral control of breathing appears to be involved in the maintenance of body homeostasis by modifying the respiratory output through respiratory sensations.


[Dyspnea sensation during resistive loading]. To examine the relationship among the sensation of dyspnea, the respiratory muscle oxygen consumption (VO2 resp), minute ventilation and occlusion pressure, seven normal volunteers were studied during incremental dead space loading induced hyperventilation with and without inspiratory resistive load. Although the sensation of dyspnea and VO2 resp at the same level of minute ventilation increased with an increase in resistance, there appeared to be a unique relationship among the sensation of dyspnea, VO2 resp and occlusion pressure, which was not affected by inspiratory resistive loading from 0 to 20 cmH2O/l/sec. These results show that the ventilatory command signal is closely related to the dyspnea sensation. We also found that during incremental dead space loading the quality of the sensation changed relatively quickly at some point, where tidal volume was maximum with each resistive loading and the breathing pattern changed. In the other experiment, the functional residual capacity (FRC) decreased during inspiratory resistive and elastic loading. Because the decreased FRC was associated with the decrease in the dyspnea sensation, it was speculated that the subject decreased his FRC through a cortical response so that the sensation of dyspnea during loading decreased.


[Relationship of respiratory muscle fatigue and respiratory effort sensation: mechanisms and treatment]. We investigated whether fatigue of the expiratory muscle may account for a change in the respiratory effort sensation in normal subjects. We also examined the effects of inspiratory muscle training (IMT) and a beta 2-agonist, fenoterol, on respiratory effort sensation during loaded breathing. Experiment 1: Expiratory threshold loading was performed until exhaustion or 30 min, to induce expiratory muscle fatigue. The respiratory effort sensation was scored using a modified Borg scale. The maximum static expiratory pressure during loading (PEmaxload) decreased with time, and the Borg score rose with time. The relationship between the sensory score and PEmaxload was virtually linear. Experiment 2: Twice daily, IMT was performed using a pressure threshold device for 15 min in each session. The inspiratory threshold was set to 30% of each subject's maximum inspiratory pressure (Plmax) and IMT was continued for 4 weeks. Respiratory sensation (Borg score) was evaluated during a progressive exercise test. IMT increased inspiratory muscle pressure by 30%. However, there was no change in Borg score during the exercise test. Experiment 3: Fenoterol (5 mg) was given 2 hours before the inspiratory threshold loading, and then threshold loaded breathing was continued until exhaustion or 60 min. Endurance time increased by 50% in fenoterol group compared to placebo group. The increase in Borg score with time was less in fenoterol group than in placebo group. The decrease in respiratory muscle strength after loading was comparable in both groups. We conclude that the increased respiratory effort sensation during expiratory threshold loading is closely related to expiratory muscle fatigue as indicated by the decrease in expiratory muscle force.(ABSTRACT TRUNCATED AT 250 WORDS)


[Relationship between anaerobic threshold and breathlessness during exercise]. We studied the possibility that during incremental exercise anaerobic threshold (AT) is associated with an increase in breathlessness in subjects with increased impedance or respiratory system. Six patients with chronic lung diseases (CLD) and six healthy subjects performed cycle ergometer exercise under two conditions; with free resistive loading and with 9 cmH2O/l/sec of inspiratory resistive loading (IRL). Ventilation, respiratory pattern, VO2, VCO2, were measured every 15 sec by a metabolic cart, Minato Respiromonitor RM 300. AT was determined by V-slope method. Mouth occlusion pressure (P0.1) was also measured in six subjects during exercise. The subjects selected a number of modified Borg scale (psi) to express their breathlessness during exercise by pushing a electrically potentiated remote button. Slopes of changes in psi with increasing work-load, delta psi/delta watt-slope, were calculated before and after V-slope AT, and each inflection point of VE, respiratory rate, VT/Ti, and VCO2. In order to evaluate which parameters are the most responsible for a change in psi, statistical significance (P-value) in changes of slope of each parameters were compared. The delta psi-slope increased with the highest significance after AT point. Under IRL the significance was more pronounced. There was a highly significant linear correlation between P0.1 and psi during exercise both under free resistive loading and IRL. In addition the increase of P0.1 with incremental exercise was characterized by a presence of inflection at a workload of V-slope AT in most of the subjects. From these results it was concluded that anaerobic threshold was closely associated with an increase of breathlessness during exercise via enhancing respiratory motor command.(ABSTRACT TRUNCATED AT 250 WORDS)


[Relation between dyspnea and personality in patients with pulmonary emphysema and healthy subjects]. To determine whether personality is related to dyspnea sensation, 19 healthy males and 17 male patients with pulmonary emphysema were tested for modified visual analog scale (VAS) during hypoxic and hypercapnic interventions. Personality was tested by both Yatabe-Guillford test and manifest anxiety scale. VAS score correlated positively with anxiety score during hypercapnia and inspiratory resistive loading under hypercapnia in healthy subjects. In patients, anxiety score correlated positively with VAS scores during hypoxia, hypercapnia, and resistive loading under hypercapnia. Scores for nervousness and cyclic tendency correlated with VAS scores during hypoxia and hypercapnia in patients. These results indicate close relation between anxiety and dyspnea in healthy as well as emphysematous subjects. In emphysema, nervousness and cyclic tendency are the additional determinants for dyspnea.


[Dyspnea and rib cage distortion in postural changes]. We studied the topographical ventilatory motion and electrical muscle activity (EMG) of intercostal muscle within the rib cage for the patients complaining dyspnea produced mostly by their postural changes. There were inappropriateness between the rib cage motion and EMG and this inappropriateness was closely related to a sensation of dyspnea. We could relieve partly dyspnea by applying the negative pressure ventilator, because of prevention of a distortion of rib cage. Based on these clinical observation, we concluded that one of mechanism to sense dyspnea was the inappropriateness between motion and electrical muscle activity within the rib cage.


[A study of chest X-ray classification of farmer's lung--correlation between X-ray pattern and background factors]. Patients with farmer's lung were classified into five groups according to their chest X-ray pattern, and the background of each group was studied with respect to stage, severity, and prognosis. Type I group, which has fine nodular shadows on chest X-ray, showed a significantly high percentage of lymphocytes in BAL cells (p less than 0.01). Type V group, which has irregular patchy shadows on chest X-ray, showed increased peripheral WBC counts, increased CRP score, and decreased PaO2 compared to the other groups. Type II, III, and IV groups, which are characterized by combined X-ray patterns such as nodular shadows, ring-like shadows, and irregular pulmonary markings, had no specific background features according to our study. Our results suggest that type I and type V groups are likely to represent acute phase and severe phase, respectively. We could not identify any significant factors indicative of chronic disease in terms of restrictive and diffusion impairment of pulmonary function tests and pathologic findings obtained by TBLB. The chest X-ray classification we proposed is useful for the diagnosis of the acute and severe stages of farmer's lung.


[Relationship between clinical symptoms and nocturnal oxygen desaturation in sleep apnea syndrome and chronic lung disease]. Nocturnal oxygen desaturation (NOD) is commonly seen not only in sleep apnea syndrome (SAS) but also in chronic lung disease (CLD) including chronic obstructive lung disease even without sleep apnea. However, the relationship of NOD to clinical symptoms such as morning headache, sleep deprivation due to breathlessness, and daytime sleepiness is not known. In this study, we examined by polysomnography the relationship between several NOD indexes, parameters of apnea, and subjective symptoms in 25 patients with SAS and 22 patients with CLD. In addition, the relation between daytime arterial blood gas data and NOD indexes, parameters of apnea, was examined. In the SAS group, there were no differences in any parameters of NOD and apnea between patients with subjective symptoms and those without symptoms. However, in the CLD group, symptomatic patients had significantly lower lowest SaO2, higher mean SaO2, and longer total desaturation time. In both groups, daytime PaCO2 had a significant correlation with several NOD parameters such as mean SaO2, lowest SaO2, and total desaturation time. In the SAS group, daytime PaCO2 was also correlated with the parameters of apnea. On the other hand, daytime PaO2 was significantly correlated with mean SaO2 only in the CLD group. From these data, we conclude that in patients with SAS, daytime PaCO2 is a variable that is related to the degree of NOD, and that in patients with CLD, subjective symptoms and daytime PaO2 in addition to daytime PaCO2 are associated with NOD.


[Probucol inhibits tobacco smoke-induced decrease in plasma anti-elastase activity and ferroxidase activity in rats]. Elastolytic enzymes and active oxygen species derived from leukocytes and alveolar macrophages during exposure to tobacco smoke, together with active oxygen species directly derived from tobacco smoke, are thought to play a crucial role in the pathogenesis of pulmonary emphysema by inactivating alpha 1 protease inhibitor (alpha 1 PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smoke-induced decrease in plasma anti-elastase activity (EIA) and ferroxidase activity (FA) in conscious venous catheter instrumented rats. Rats exposed to the smoke of 5 cigarettes (nicotine 11 mg, tar 115 mg) in a plastic chamber showed a prompt increase in plasma COHb to 17.9 +/- 2.7%, and a prompt decrease in plasma EIA by -17.9% (p less than 0.05) and FA by -14.8% (p less than 0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normal cholesterol plasma levels, and rats administered probucol for 4 weeks showed hypocholesterolemic plasma levels. EIA and FA were not depressed after smoking, and lipid peroxide product (TBA reactive substance) in lung tissue (p less than 0.05) and serum (p less than 0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p less than 0.01) compared with control rats. These results indicate that probucol, via its antioxidant action rather than its cholesterol lowering effect, has a protective effect on lung exposed to tobacco smoke in terms of protease-antiprotease balance and oxidant-antioxidant balance.


[Manipulation, premedication, and chemoprophylaxis for fiberoptic bronchoscopy]. Manipulation, premedication, and chemoprophylaxis for fiberoptic bronchoscopy vary among institutions. We analyzed the actual conditions by means of a questionnaire distributed to 29 institutions. With regard to premedication, a combination of atropine sulfate and sedatives, such as hydroxyzine hydrochloride, was the most common method. In cases with heart disease and elderly subjects, a lower dosage or omission of atropine was common. In cases with marked anxiety, narcotics were prescribed. Bronchofiberscopic examination was performed under local anesthesia at all institutions. Lidocaine 4% was used for anesthesia of the orolarynx, and 2% was used for the tracheobronchus. For prophylaxis of infection, 19 of 29 institutions prescribed antibiotics routinely or under certain circumstances. ECG was used in 14 institutions, and percutaneous oxygen monitoring in 5 institutions. It is concluded that the manipulation and premedication for fiberoptic bronchoscopy vary between institutions. It is necessary to determine more efficacious and safer methods for fiberoptic bronchoscopy.


[Malignancies in patients with sarcoidosis]. We evaluated the occurrence and type of malignant tumors in 148 patients with sarcoidosis followed at the Okayama University Hospital. Nine patients had malignancies; in 2 of 9 patients the development of malignancy preceded that of sarcoidosis, and one patient presented with sarcoidosis and malignancy at the same time. Six patients developed six types of malignancy following the development sarcoidosis; one case each of stomach cancer, lung cancer, breast cancer, thyroid cancer, testicular tumor, laryngeal cancer, and chronic lymphocytic leukemia. There was no significant difference between sexes (3 males and 3 females). The mean age of the cancer group at the onset of sarcoidosis was 56 years, which was significantly higher (p less than 0.05) than that of the control group. In these 6 patients, the mean interval from onset of sarcoidosis to detection of cancer was 11.7 years (range 1.5 to 30.2 years). The relative risk of malignancy was calculated based on the data for 148 patients with sarcoidosis with a total of 1371 person-years. The expected incidences of cancer for all sites and specific sites were estimated by applying age- and sex-adjusted person-years. The observed incidence of cancer was significantly (p less than 0.05) greater than the expected incidence for thyroid cancer, laryngeal cancer, and leukemia. No significant difference in incidence was found for all sites or for the other sites of cancer. The increased cancer incidence in sarcoidosis may be secondary to immunological abnormalities associated with this disease.


[Long-term effects and complications of home nasal CPAP therapy for obstructive sleep apnea patients]. We treated 23 patients with obstructive sleep apnea syndrome (OSAS) by nasal continuous positive airway pressure (NCPAP) at home, and examined the long-term compliance, clinical effects, and complications after NCPAP therapy. Nineteen patients continued and four patients discontinued the therapy during the mean observation period of 15 months, and the compliance was 83%. There was no significant difference in age, weight, and sleep data between the compliant group (C) and non-compliant group (NC). The causes of discontinuation of therapy were lack of adaptation to the apparatus (2 cases), improvement of clinical symptoms due to weight reduction (1 case), and induction of asthma attack (1 case). Disappearance of excessive daytime sleepiness, improvement of sleep quality, and disappearance of nocturia were observed in most cases, and disappearance of morning headache and improvement of sexual ability and emotional instability were also observed in several cases. Nine cases (39%) complained of discomfort due to the nasal mask and 6 cases (26%) complained of dryness of the mouth and nose, whereas 10 cases (43%) experienced no adverse effects. No serious complications were observed. These findings suggest that long-term home NCPAP is an effective and safe treatment for OSAS patients.


[Endoscopic endobronchial metastasis].

[Endoscopic endobronchial metastasis]. Although the incidence of endobronchial metastasis in cases of extrathoracic tumors is 2 to 5 percent in autopsy reports, it is about 30 percent according to endoscopic examination (so-called endoscopic endobronchial metastasis). To confirm the nature of endoscopic endobronchial metastasis, we reviewed the records from 1980 to 1990, presuming the primary foci of metastasis. Of the 36 patients with metastatic pulmonary tumor, 6 (16.7%) were diagnosed as having endobronchial metastasis endoscopically. The primary tumors were colonic cancer (2), prostatic cancer (2), cancer of the tongue (1), and renal cell carcinoma (1). The chest X-ray findings were nodular shadow (3), atelectasis (2), and hilar lymphadenopathy with atelectasis (1). Three patients were treated by lobectomy and the others by systemic therapy alone. The presumed primary foci of metastasis were peripheral lung (3), mediastinal lymph node (1), and undetermined (2). The results of the present study suggest that so-called endoscopic endobronchial metastasis does not necessarily imply metastasis to the bronchial wall.


[Bronchoalveolar lavage fluid findings in rheumatoid arthritis]. Findings of bronchoalveolar lavage fluid (BALF) were compared among three groups of patients: rheumatoid arthritis (RA) with or without interstitial lung disease (ILD), and collagen disease other than RA accompanied by ILD. Regardless of the presence or absence of associated ILD, the RA groups showed higher numbers of neutrophils in BALF with a mean number about 10 times that of the collagen disease group. In contrast, the percentages of lymphocytes in the RA groups were lower than that in the collagen disease group. Classification of alveolitis on the basis of BALF findings revealed neutrophil type (N) in 55% of the RA patients and lymphocyte type (L) in 25%. In the collagen disease group, N was found in 15.4%, and L in 38.5%. Regarding the lymphocyte subsets, many patients with RA accompanied by ILD had a CD 4/8 ratio of 1 or great. These findings suggest that highly characteristic neutrophil alveolitis is present in the pulmonary interstitium from the initial stage of RA.


[Percent home stay, an index for the clinical evaluation of home oxygen therapy]. To evaluate the usefulness of % home stay as an index for evaluation of the clinical effects of long term home oxygen therapy (HOT), we retrospectively examined 70 consecutive cases with chronic respiratory failure treated by HOT in the Ogaki area. The clinical data, underlying diseases, and survival rate of the cases were similar to recent official statistics in Japan; thus, we considered these cases to be a representative population. For evaluation, we tentatively used a % home stay of 70% as the standard level, which was determined by the 25th percentile line. To examine the usefulness of this standard, we classified the study population into 2 groups (the group with % home stay of greater than 70% (Group A, n = 54), and the group with % home stay of less than 70% (Group B, n = 16)), and compared the outcomes, survival rates, life situations, and background factors between these groups. As a result, there were significant differences in outcome (at home 34%, hospitalized 11%, and dead 22% in group A, and 6%, 44%, and 50%, respectively in group B, p less than 0.05), survival rate (p less than 0.05 by logrank test), and life situation between these groups. Thus, a % home stay of 70% is thought to be a useful standard for clinical evaluation, because it reflects both the prognosis and quality of life of patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[A study of epithelioid cell granulomas in transbronchial lung biopsy specimens of sarcoidosis patients--correlation between granulomas and clinical activity or chest X-ray lesions]. The 565 pulmonary tissue specimens taken from 155 sarcoidosis patients by transbronchial lung biopsy (TBLB) were studied by light microscopy. Particular attention was paid to the mean number and type of epithelioid cell granulomas, the mean number of giant cells, and the degree of lymphocyte cuffing, perigranulomal fibrosis, and granuloma confluence. The granulomas were divided into three types, hypertrophic, atrophic, and hyalinofibrous. In stage II and III patients, the mean number of granulomas and giant cells, the positive rate of hyalinofibrous granuloma, the relative proportion of the hyalinofibrous granuloma group, and the degree of fibrosis and confluence were significantly higher than those in stage O and I patients. The mean number of granulomas was related to the serum level of angiotensin converting enzyme and 67Ga uptake into lung parenchyma, but not to the cellular findings of bronchoalveolar lavage fluid (BALF). The lymphocyte count of BALF in the hypertrophic granuloma group was significantly higher than that in the atrophic and hyalinofibrous granuloma groups. CD4/CD8 ratio of lymphocytes in BALF was significantly lower in the hyalinofibrous granuloma group than in the other groups. In stage I patients, the resolution of intrathoracic lesions on chest X-ray was significantly more frequent in the atrophic granuloma group than in the hypertrophic granuloma group, 2 and 5 years after TBLB was performed. The pulmonary lesions had a tendency to persist for a long time in stage II and III patients with hyalinofibrous granuloma or granuloma confluence. Newly appearing pulmonary lesions showed hypertrophic granulomas as well as marked lymphocyte cuffing.


[A case of obstructive sleep apnea syndrome with increased lung water content during sleep]. A 57-year-old man was admitted complaining of sleep disturbance. All night polysomnography showed a pattern of obstructive sleep apnea. We performed 201Tl scintigraphy to evaluate hemodynamic change and degree of stress on the right ventricle during sleep, and compared it with a 201Tl scintigram during wakefulness. We recognized 201Tl uptake by the lung in the 201Tl scintigram during sleep, but not during wakefulness. To determine the mechanism of 201Tl uptake by the lung during sleep, we measured lung water content during sleep by double indicator dilution method (Nihon Koden, NTV-1100). We recognized an increase of lung water content during sleep. We consider that the increase of lung water content during sleep is caused by sleep apnea, probably by hemodynamic change due to negative pleural pressure swings during sleep apnea.


[A case of flomoxef-induced pneumonitis]. We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan.


[An autopsy case of sarcoidosis associated with renal failure]. A 62-year-old woman presented with uveitis and abnormal chest X-ray (bilateral hilar adenopathy). Skin biopsy in 1983 had revealed non-caseating epithelioid cell granuloma consistent with sarcoidosis. Her serum biochemical investigations and exploratory laparoscopy suggested nodular liver cirrhosis, but biopsy was not performed. Both blood urea nitrogen (BUN) and serum creatinine values were within normal limits. She received prednisolone therapy of 15 mg daily initially, and later a maintenance dose of 5 mg daily. In 1985, she complained of skin itching and her laboratory data revealed severe renal insufficiency (BUN 97 mg/dl, serum creatinine 12.2 mg/dl) and hypercalcemia (corrected serum calcium level: 11.5 mg/dl). Prednisolone treatment (40 mg daily) resulted in a dramatic improvement of renal function as well as other clinical abnormalities due to sarcoidosis, without any significant changes in liver function. She died of cerebral infarction in 1989. Autopsy showed interstitial nephritis with tubular calcinosis and hyalinized glomeruli. It is postulated that hypercalcemia due to sarcoidosis contributed to the renal failure in this patient. This case suggests that renal damage due to sarcoidosis may be reversible with appropriate corticosteroid therapy.


[A case of aspirin-induced asthma due to ketoprofen adhesive agent]. A 40-year-old woman who had been diagnosed as having aspirin-induced asthma was admitted with stridor. She had a history of surgery for sinusitis and nasal polyps, and severe asthmatic attack requiring mechanical ventilation after administration of puranoprofen (Niflan). On the second day of hospitalization, she used a ketoprofen adhesive agent (Miltax, 30 mg) for a stiff shoulder. Stridor developed five hours later, progressing to a severe asthmatic attack with loss of consciousness, requiring mechanical ventilation. The serum level of ketoprofen was very high (81.7 ng/ml); therefore, provocation challenge test was performed to confirm the possible relationship between the ketoprofen adhesive agent and asthmatic attack. After closed patching of the agent (15 mg) on her lower leg, stridor developed, and FEV1.0 and PFR decreased, in association with an increase of the serum level of ketoprofen to a maximum of 38.0 ng/ml. These results show that the topical application of a ketoprofen adhesive agent induced the asthmatic attack by transdermal absorption in this patient.


[A case of foreign body granuloma due to aspiration of a twig of Cryptomeria]. A 65-year-old man was admitted to Oita Medical School Hospital with complaints of hemoptysis and left anterior chest pain. Chest X-ray film showed a nodular shadow, about 1 cm in diameter, in the left S8 area. A specimen obtained by transbronchial biopsy showed no malignant findings. However, left lower lobectomy was performed because of the possibility of malignancy. The resected specimen contained a twig of cryptomeria within dark-red lung tissue. Histologically, the foreign body granuloma was surrounding a vegetable fiber. We had no information of an episode of pruning a cryptomeria and aspiration of a twig before the operation. Cryptomeria is an extremely rare bronchopulmonary foreign body, and the present case suggests that bronchopulmonary foreign body granuloma is an important disease in the differential diagnosis of pulmonary nodules.


[A case of pulmonary infiltration with eosinophilia (PIE) syndrome induced by Saiboku-To (TJ96). Detection of ECF activity in lymphocytes stimulated with TJ96]. A case of PIE syndrome induced by Saiboku-To (TJ96) is reported. A 56-year-old woman had been treated for intractable bronchial asthma since the age of 42 years. She had a history of PIE syndrome induced by disodium cromoglycate 4 years previously (Jpn. J. Thoracic Disease, 27.1.1989). To reduce the dose of prednisolone for her asthma, administration of TJ96 was started in Dec. 1989. After 5 months of TJ96 treatment, she developed dry cough, fever, and chest pain. Physical findings and laboratory examinations revealed pulmonary infiltrations in the right lung field and severe eosinophilia. Because of suspected drug-induced PIE, TJ96 was stopped and 30 mg/day prednisolone was administered. Her symptoms and laboratory abnormalities subsequently resolved. To confirm the diagnosis of drug-induced PIE syndrome, drug-induced lymphocyte stimulation tests with TJ96 and other drugs were performed. TJ96 significantly induced lymphocyte blastogenesis with a stimulation index of 6.1. Moreover, the supernatant of the incubation mixture of TJ96 and peripheral lymphocytes from the patient showed marked eosinophil chemotactic activity. To our knowledge, there has been no previous report of PIE syndrome induced by TJ96. In addition, this is the first report of the detection of ECF activity in lymphocytes induced by an offending drug in vitro.