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By affinity chromatography with Sepharose coupled to 2'-deoxy-1-beta-D-ribofuranosyl-N4-dodecanoylcytosine, deoxycytidine kinase and cytidine deaminase were purified 1,950- and 2,240-fold, respectively, from Ehrlich carcinoma cells, and their enzyme activities for several deoxycytidine analogs were investigated.

To establish the novel approach in order to distinguish the transcriptionally active androgen receptor (AR) from the transcriptionally inactive AR, we performed the three-dimensional construction of confocal microscopic images of intranuclear AR. This method clearly distinguished the subnuclear localization of transcriptionally active AR tagged with green fluorescent protein (AR-GFP) from the transcriptionally inactive AR-GFP. Transcriptionally active AR-GFP mainly produced 250-400 fluorescence foci in the boundary region between euchromatin and heterochromatin. Although the AR-GFP bound to such antiandrogens as hydroxyflutamide or bicalutamide translocated to the nucleus, they homogeneously spread throughout the nucleus without producing any fluorescence foci. Antiandrogenic environmental disrupting chemicals, such as 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, vinclozolin, or nitrofen, also disrupted the intranuclear fluorescence foci. A point mutation (T877A) resulted in the loss of ligand specificity in AR-GFP. Even in this mutant receptor, agonists, such as dihydrotestosterone, hydroxyflutamide, or progesterone, produced the fluorescence foci in the nucleus, whereas the transcriptionally inactive mutant binding bicalutamide was observed to be spread homogeneously in the nucleus. Taken together, our findings suggest that, after nuclear translocation, AR is possibly located in the specific region in the nucleus while demonstrating clustering tightly depending on the agonist-induced transactivation competence.

As part of a collaborative work, male rats were administered 1,3-dinitrobenzene (1,3-DNB) daily at 0, 25 and 50 mg/kg/day from the age of 6 weeks for 4 weeks (4-week exp.), or at 25, 50 and 75 mg/kg/day from the age of 8 weeks for 2 weeks (2-week exp.). After the end of each administration period, all survivors were sacrificed, and their testes and epididymides were removed, weighed and examined histopathologically. The following results were obtained. In the 4-week exp.: At 50 mg/kg/day, the weights of testes and epididymides showed decrease with macroscopic atrophy. The testicular spermatogenic epithelium showed decrease in the number of sperm-spermatocytes, degeneration/necrosis, giant cell formation and vacuolation, reduction in sperm counts also being evident in the ducts of the epididymides. In the 2-week exp.: At 50 and 75 mg/kg/day, the weights of testes and/or epididymides showed decrease with macroscopic atrophy. Several histopathological changes in the testes and epididymides were essentially the same changes as in the group given 50 mg/kg/day in the 4-week exp., with a clear relation. These results indicate that a 2-week administration period is sufficient to detect testicular and epididymal histopathological changes induced by 1,3-dinitrobenzene in male rats.

Deoxycytidine kinase from Ehrlich carcinoma cells was purified 10400-fold by ammonium sulfate fractionation and affinity chromatography using Sepharose 4B coupled to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine , with a yield of 45%. The purified enzyme preparation showed a single major band with a molecular weight of 32000 on SDS-PAGE. The enzyme phosphorylated deoxyadenosine, deoxyguanosine, cytidine, and several deoxycytidine analogues as well as deoxycytidine. Also, the kinetic parameters of the enzyme for the substrates were estimated.

Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced.

The gene encoding the alpha isoform of rat Ca2+/calmodulin-dependent protein kinase II was cloned, and its exon-intron organization was analyzed. The coding region of cDNA consists of 18 exons spanning more than 50 kilobase pairs. Each of the discrete functional units, such as the ATP-binding site, the autophosphorylation site responsible for Ca2+-independent activity, the calmodulin-binding site, and link structure is encoded by a single exon. The largest and smallest exons consist of 229 and 41 base pairs, respectively. All splice junction sequences flanking the introns conform to the consensus splice junction sequence and the GT-AG splice rule.

The immunotoxicity of S-1, which is a new antineoplastic agent, was investigated in BALB/c mice. S-1 contains tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molecular ratio of 1:0.4:1. 5-fluorouracil (5-FU) and UFT were used as reference drugs. S-1 and reference drugs were administered by oral gavage for 7 days. The high dose employed in this study was determined as the maximally tolerated dose of a 9-day repeated-dose study in sarcoma 180-bearing mice. Decreased body weight was observed in mice treated with 5-FU and UFT but not in those treated with S-1. A significant decrease in thymus and spleen weight was observed in S-1-, UFT- and 5-FU-treated mice, and the degree was same for the three drugs. Though the number of white blood cells decreased dose-dependently for the three drugs, S-1 had the weakest effect. The number of red blood cells also decreased, but the effect was not dose-dependent, and its magnitude was the same for the 3 drugs. S-1 induced a dose-dependent decrease in the IgM antibody PFC response to sheep erythrocytes. The delayed type hypersensitivity response used a footpad reaction method was significantly suppressed at the highest dose of S-1. 5-FU and UFT suppressed humoral and cell-mediated immunity in almost the same manner as S-1. The degree of suppressive effects was greater on the humoral immune response than on the cell-mediated immune response. The number of CFU-GM colonies was significantly decreased in the highest dose group of each drug and in a lower group as well in S-1-treated mice. This finding might reflect the fact that S-1 induced continuous high levels of 5-FU in the blood. Under these experimental conditions, S-1 induced immunosuppressive effects in BALB/c mice, and the degree of suppression was almost same as that induced by 5-FU and UFT.

The antigenicity was tested of a new antineoplastic agent S-1 (a combination of tegafur (FT), CDHP and potassium oxonate (Oxo)) in mice and guinea pigs. 1. Male BALB/c or C3H/He mice were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and human serum albumin (HSA). S-1 was administered by oral gavage, and the other compounds were administered intraperitoneally with adjuvant (alum). In the heterologous passive cutaneous anaphylaxis (PCA) test, using Sprague-Dawley rats as recipients, no IgE antibodies against S-1, CDHP, or Oxo were detected to any serum obtained from the sensitized mice, and no eliciting antigenicities were seen for CDHP or Oxo. 2. Male Hartley guinea pigs were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and HSA. S-1 was administered by oral gavage, and the other compounds were administered subcutaneously with Freund's complete adjuvant (FCA). The homologous PCA test, active systemic anaphylaxis test, and passive hemagglutination test showed no production of antibodies against S-1, CDHP, or Oxo in any sensitized guinea pig, and no eliciting antigenicities for CDHP or Oxo. 3. Female Hartley guinea pigs were sensitized with S-1 subcutaneously with FCA. The active cutaneous anaphylaxis test revealed that S-1 did not induce cell-mediated delayed type hypersensitivity. 4. These results indicated that S-1, Oxo, and CDHP were not antigenic in mice and guinea pigs.

In this paper measurements of the radionuclides of 36Cl, 41Ca, 60Co, 152Eu and 154Eu in samples from Hiroshima, which were exposed to neutrons of the A-bomb explosion, are interpreted. In order to calculate the neutron spectrum at the sample site, neutron transport calculations using Monte Carlo techniques were carried out. Activation profiles in a granite mock-up irradiated with reactor neutrons could be reproduced by this method using DS86 input parameters. The calculated neutron spectrum at the sample site for non-thermal neutrons is identical to that obtained in DS86, but contains some 50% more thermal neutrons. The influence of parameters like soil composition, source terms and air humidity on the activation of these radioisotopes is discussed. The granite-covered earth at the sample site, for example, hardens the spectrum in comparison with DS86 values. Even when using a fission spectrum pointing downward and neglecting air humidity one cannot explain our 36Cl measurements. If the effective thermal neutron fluences, that have a similar ratio of resonance integral to thermal neutron capture cross sections obtained from 36Cl, 41Ca and 152Eu, are averaged, a bomb yield of about 16 kt is deduced in agreement with a bomb yield of (15 +/- 3) kt estimated in DS86.

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The two BRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase-polymerase chain reaction (RT-PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)-1 beta expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL-1 beta levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL-1 beta is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL-1 beta production by liver macrophages, and the produced IL-1 beta activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL-1 beta by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.

Single dose toxicity studies of suplatast tosilate (IPD-1151T) were carried out in mice, rats and dogs of both sexes. The results were as follows: 1. The LD50 values of IPD-1151T were as follows: Mice, 12,500 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Mice 81 (male) and 96 (female) mg/kg in intravenous route; Rats, 10,000 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Rats, 96 (male) and 93 (female) mg/kg in intravenous route; Dogs, 2,124 (male) and 2,660 (female) mg/kg in oral route. On the LD50 values, no sexual difference was apparent in all species, but the species difference was noted between the rodent and dog. LD50 values of dog were lower level than those of rodent. 2. As toxic signs, mucous diarrhea with specific smell was noted in orally administered rodent. In addition, rats showed soiled fur in the perianal. In intravenous route, the rodent showed dyspnea, tonic convulsion and lateral position and deaths occurred within 10 min in mice and within 30 min in rats after administration. Dog showed toxic signs similar to those in rodents and deaths occurred within 3 hours. 3. In pathological examinations, dead mice and dogs administered orally showed lung congestion, liver fading or slight hemorrhage in the endo-and/or exocardium. Dead rodent administered intravenously showed only slight hemorrhage and congestion in the lung. Alive mice, rats and dogs showed no remarkable changes. 4. The main cause of deaths seemed to be respiratory disturbance in all species.

Accelerator mass spectrometry was performed at the Munich tandem laboratory to determine 36Cl/Cl ratios of samples from a tombstone exposed to neutrons from the Hiroshima bomb. The ratios were determined from the surface to deeper positions. The depth profile of 36Cl/Cl can be used for estimating the neutron energy distribution and intensity near the hypocentre in Hiroshima.

Fifty-three Japanese children with non-rheumatic myocarditis were investigated with regard to left ventricular hypertrophy (LVH), which was assessed electrocardiographically. Follow-up periods ranged from 12 to 58 months with a mean of 22.8 months. Left ventricular posterior wall thickness (LVPWT) evaluated echocardiographically was compared to the electrocardiographic findings of LVH. The overall prevalence of LVH was 30.2% (16 patients). In 3 patients, LVH was detected during the first examination. In the other patients, however, LVH was detected later during the follow-up periods. In all but 2 patients, LVH disappeared during the follow-up periods. The development into hypertrophic cardiomyopathy was evident in only one patient. The LVPWT showed no definite relation to the presence of LVH. Thus, LVH on an electrocardiogram appears to be a common finding in children with non-rheumatic myocarditis.

Titers of antideoxyribonuclease-B (ADNB, by Streptonase-B test), antistreptolysin-O (ASO, by Rantz-Randall's micromethod) and Kinase test (antivaridase agglutination test) were performed on 118 sera of patients with suspected streptococcal infection and compared. Between ASO and ADNB, a fairly significant correlation was seen (r = 0.69), but many cases in which ADNB exceeded ASO were observed. Between Kinase and ADNB, no significant correlation was seen (r = 0.49). Successive determination of antibody titers were made in 14 consecutive patients with acute glomerulonephritis, anaphylactoid purpura nephritis, rheumatic fever and chronic rheumatic heart disease. In general, ADNB titer was significantly higher than ASO with few exceptions. The duration of high titer of ADNB was much longer than ASO Kinase titers were sometimes unstable. Throughout this study it has been noted that the result of ADNB was very easily to read and was highly reproducible. There were no nonspecific or pseudopositive reactions. Therefore, ADNB is useful for the diagnosis of streptococcal infection and its complication especially when other antibody titers give negative or doubtful results.

A 68-year-old male, who had advanced rectal cancer with multiple pulmonary metastases, had undergone resection of rectal cancer operatively and was treated with a combination chemotherapy using 5'-DFUR (5'-deoxy-5-fluorouridine) and MMC (mitomycin C) for multiple pulmonary metastases. Nine months from the start of this therapy, pulmonary metastatic lesions disappeared completely on chest X-ray examination and computed tomography. This case corresponded to complete response (CR) according to the response criteria proposed by Koyama-Saitoh. No significant side effects were observed during this chemotherapy. From the results in this case, the combination chemotherapy was considered to be one of the effective antineoplastic therapies available for pulmonary metastasis from large bowel cancer.

IgE-mediated histamine release from whole blood was analyzed in 44 patients with bronchial asthma by observing maximum present release and dose-response curves of histamine release induced by anti-IgE and house dust extract. The maximum histamine release from whole blood induced by anti-IgE correlated with total serum IgE levels. There was a close correlation between allergen-induced release from whole blood and the serum levels of specific IgE antibodies. In the maximum histamine release from whole blood induced by both anti-IgE and allergen, the interaction with a serum factor was not clearly recognized. Effect of a serum factor was shown in the dose-response curves of anti-IgE-induced histamine release, but not in those of allergen-induced histamine release. The dose-response curves caused by anti-IgE showed that basophils from cases with a high serum IgE level require much more anti-IgE to produce maximum histamine release than basophils from cases with a low serum IgE level. The results showed that IgE molecules contained in the serum participate in anti-IgE-induced histamine release from whole blood.

Cefoperazone (CPZ) has a broad antibacterial spectrum against Gram-positive, -negative aerobic and anaerobic organisms, it is also highly active against Pseudomonas sp. and Enterobacter sp. which are hardly susceptible to current cephalosporins. The clinical studies on CPZ were performed in postoperative wound infections and abdominal cavity infections, and the following results were obtained. Overall clinical effect: The rates of effectiveness were 100% in postoperative wound infections and 71.4% in abdominal cavity infections. Bacteriological effect: The rates of eradication were 90% in postoperative wound infections and 80% in abdominal cavity infections. Side effects: Any side effects on marked changes in laboratory findings were not observed in any of the cases treated with CPZ. Based on the above results, we considered that CPZ is a highly useful antibiotic for the treatment of postoperative infections.

Candida albicans-induced histamine release from basophils was studied in 54 patients with bronchial asthma in comparison with the release caused by house dust and anti-IgE. The release of histamine induced by C. albicans and that induced by house dust were closely related to the serum levels of specific IgE antibodies as expressed by RAST scores. A correlation of C. albicans-induced histamine release with the release caused by anti-IgE was not generally observed. On the other hand, a close correlation was found between house dust- and anti-IgE-induced histamine release. It was suggested from these results that the differences between C. albicans- and house dust-induced histamine release might be due to the different antigenicity of the two allergens.

The correlation between blood eosinophilia and anti-IgE-mediated histamine release was investigated in 22 bronchial asthma patients with peripheral eosinophilia (over 8%). In the cases (Group A-1 and Group A-2) in which house dust was the specific antigen, significant histamine release from basophils was induced by anti-IgE and house dust. The result indicates a relationship between eosinophilia and the IgE-mediated mechanism of disease onset. In the cases (Group A-3) with RAST scores of 0+ and 1+ to house dust, the anti-IgE-induced histamine release varied from low to high percentages, and the participation of the IgE-mediated pathway was indicated in some cases. In the cases (Group B) with negative skin reactions, few patients had a family history of allergic disease. Their ages at onset were higher, and they demonstrated lower total IgE levels. These cases showed an extremely low percent of histamine release from basophils, which indicated the absence of a correlation between eosinophilia and IgE-mediated mechanisms.

A follow-up study of childhood myocarditis for at least 12 months (12--39 months, average 19.7 months) was made on 26 patients. Regular cardiological examinations (X-ray, ECG, PCG, MCG and UCG) and serum enzyme studies (especially LDH isozyme and CPK isozyme) were done. Clinical and cardiological normalization was seen in 13 (50.0%), not necessarily with normalized enzyme study. Major residual abnormalities were: CRBBB (3), VPC (3), abnormal Q (1), A-V block I (1), large IVth sound (1) and chronic nonobstructive cardiomyopathy (HNCM) (1). Mild, transient recurrences were seen in 3. Enzyme abnormalities, which existed at the first visit in all cases, disappeared only in 12. This suggests that somewhat active inflammatory process may persist for years, even after clinical and cardiological normalization. The patient with HNCM had a heavy familial history of cardiomyopathy. The relationship between myocarditis and cardiomyopathy was discussed. It is necessary to examine every patients with cardiomyopathy from the stand of view of myocarditis.

Sixty-eight patients of clinically diagnosed myocarditis, 0--15 years of age, were followed up and analyzed. Forty (58.8%) were males. The majority were older than 5 years. Clinical courses were rather mild, chronic and self-limiting at large. Only 1 case had a relation to chronic cariomyopathy. Exertional symptoms (chest pain, chest distress, syncope) were seen in 25 (36.8%). ECG changes were very common: the majority were nonspecific ST elevation, depression or both, mainly in leads II, III, V5 and V6. Positive Master' test, prolonged QTc, widened mean spatial QRS-T angle and various arrhythmias were also observed. Cardiac performance, estimated by echocardiogram and phono-mechanocardiogram was lowered in 41 (60.3%). Large IV sound and large A wave in apexcardiogram were also frequently found. All but 3 patients showed continuous elevation of serum enzymes, namely, LDH, LDH-1/LDH-2, CPK, CPK-MB, HBD and GOT. Etiological evidences were obtained by serological study in 11 cases (16.2%): 2 of Coxsackie B-1, 3 of Coxsackie B-2, 1 of Coxsackie B-4, 2 of mycoplasma pneumoniae, 1 of cytomegalovirus, 1 of ECHO-7 and 1 of rubella. We proposed a criteria for diagnosis of myocarditis as follows: (1) Exertional symptoms. (2) ECG findings. (3) Serum enzyme abnormality. (4) Lowered cardiac performance. (5) Cardiomegaly. (6) Changing character of all signs and symptoms.

Anti-IgE-induced histamine release from basophils was examined in 46 asthmatic subjects using a whole blood method. Basophils from subjects less than 30 years old released more histamine than those from subjects aged 41 to 50. The age at onset of the disease also affected the reactivity of basophils to anti-IgE: basophils showed a high response in subjects whose age at onset was between 0 and 10 years, and low response in the subjects whose age at onset was between 41 and 50 years. There was a correlation between histamine release and serum IgE levels. However, individual dose-response curves of histamine release varied greatly in whom serum IgE levels were low.

Seventy-one cases of bronchial asthma were classified into three types: bronchospasm, bronchospasm-hypersecretion and bronchiolar obstruction types. The characteristics of each type were studied in relation to patient age and age at onset of the disease. In the 71 subjects studied, the most frequent type was the bronchospasm type followed by the bronchospasm-hypersecretion type and bronchiolar obstruction type. Intractable asthma was most frequently observed in the bronchiolar obstruction type and least in the bronchospasm type. Most of the patients under 50 years of age showed the bronchospasm type. The bronchospasm-hypersecretion type was characteristically accompanied by blood eosinophilia when the patient age was under 50 years. In the bronchospasm-hypersecretion type, the incidence of intractable asthma was high in patients under 50 years of age, but not remarkable in those over 50. A large proportion of the patients over 50 years of age were of the bronchiolar obstruction type. There was no difference in the incidence of intractable asthma between the two groups classified by age at onset.

In order to evaluate the long-term-safety of halopredone acetate (THS-201: 17 alpha, 21-diacetoxy-2-bromo-6 beta, 9 alpha-difluoro-11 beta-hydroxy-1, 4-pregnadiene-3, 20-dione), a 52-week chronic toxicity study was performed on the basis of its local accumulation in dogs. In doses of 0.1, 0.5 and 2.5 mg/kg, THS-201 was injected into the right knee joint in both sexes of dogs every 2 weeks for 39 weeks and withdrawn for 13 weeks. In this study, the below slight local changes were observed in both sexes of dogs treated with 2.5 mg/kg/2 weeks of THS-201: focal loss of hair of the injection site, lesser stain in cartilage matrix of articular cartilage and meniscus in light microscopic examinations, and irregular thickness and elongation of collagen fibers, roughness of fibrous density and decrement of proteoglycans in electron microscopic examinations. In conclusion, systemic adverse effects were not observed in any dogs treated with THS-201.

Acute toxicity studies of propiverine hydrochloride (P-4) were carried out in mice, rats and dogs of both sexes. 1. The LD50 values of P-4 were as follows: Mice; 410 (male) and 323 (female) mg/kg in oral route, 223 (male) and 283 (female) mg/kg in subcutaneous route and 36 (male and female) mg/kg in intravenous route, Rats; 1000 (male) and 1092 (female) mg/kg in oral route, 1632 (male) and 1411 (female) mg/kg in subcutaneous route, and 22 (male) and 25 (female) mg/kg in intravenous route. On the LD50 values, no sexual difference was apparent but the species difference between mice and rats observed to be present in oral and subcutaneous routes. The approximate lethal doses of P-4 in dogs were 987-1137 mg/kg for male and 865-894 mg/kg for female in oral route, and the values were almost same as those in rats of oral route. 2. Major toxic signs such as clonic convulsion, bradypnoea, dyspnoea, decreased spontaneous activity and hematuria were observed in mice and rats. Furthermore mydriasis in rats, and transitory salivation and/or vocalization in mice and rats were observed. In some rats, sedation, salivation, soil at hypogastrium, rale and emaciation were detected from the next day of oral administration. In dogs, toxic signs such as vomiting, tremor, tonic and/or clonic convulsion, mydriasis and gasping were observed. 3. Pathological changes observed in dead animals were congestion of lungs, liver and kidneys in all routes, congestion and hemorrhage in digestive tracts in oral route, inflammatory changes at the injection site in subcutaneous route. In addition, retention of hematuria in urinary bladder in rats of oral and subcutaneous routes, the hemorrhagic changes of heart, atonia of urinary bladder and retention of urine in dogs were observed. 4. The main cause of death seemed to be respiratory disturbance in all species and the weakness in a few rats of oral route.

The inhibitory effect of nicardipine, a calcium antagonist, on the antigen- and anti-IgE-induced histamine release from basophilic leucocytes of patients with bronchial asthma was examined. The agent significantly inhibited both antigen-stimulated and anti-IgE-induced histamine release from basophils (the maximum percent inhibition was 57.8 +/- 7.2% and 56.0 +/- 8.8%, respectively). Pre-incubation of basophils with nicardipine for periods of up to 120 min did not alter the inhibitory effect. These results suggest that nicardipine modifies the histamine release from basophils which closely participate in an attack of bronchial asthma.

The release of histamine by allergen and anti-IgE from whole blood was observed in 34 asthmatic subjects with a positive skin test to house dust. The time course of histamine release showed that the release by allergen and anti-IgE peaked after 15 min incubation. There was no significant difference in the time course of the release from whole blood between allergen and anti-IgE. Anti-IgE-induced histamine release correlated to a certain extent with the serum IgE level. Histamine release by house dust, on the other hand, correlated with the radioallergosorbent test score. A striking difference was present in the dose-response slope between allergen and anti-IgE. The maximum percent release correlated with the dose-response slope by allergen, but not by anti-IgE. The amount of histamine release induced by anti-IgE paralleled the amount of the release by house dust in the cases sensitive to the allergen; less sensitive basophils to anti-IgE were less sensitive to house dust.

A clinical study was performed on concentration of cefotiam (CTM) in the gallbladder bile and the gallbladder tissue in benign diseases of the biliary tract. By an hour intravenous infusion the CTM concentration obtained 2 hours after the start of the infusion revealed that the level of the CTM in A bile was atmost same as that in B bile (3.1--46.0 micrograms/ml). The concentration in gallbladder tissue was 5.7--116 micrograms/ml. In addition, the CTM level was higher enough than the MIC of CTM covering more than 80% of the strains of E. coli and Klebsiella obtained from the focus. From these results, it is concluded that CTM is clinically effective and useful in the case of biliary disease.

DNA polymerase alpha activity is associated with cell proliferation, independently of the cell cycle phase, and a simple and reproducible method for the immunohistochemical demonstration of DNA polymerase alpha has been developed. In an analysis of a total of 76 human breast cancer tissues using this procedure, the clinico-pathological findings revealed that only the estrogen receptor (ER) significantly correlated with the DNA polymerase alpha activity. Therefore, this suggests that ER-negative tumors had a higher proliferative activity.

Basophil histamine release induced by allergens (house dust and Candida albicans) and anti-IgE was examined in 31 patients with bronchial asthma in relation to patient age, age at onset of the disease and serum IgE levels. Basophils from patients under 40 years of age generally released a significantly large amount of histamine by stimulation with house dust and anti-IgE. On the other hand, histamine release from patients over 41 years of age was generally not marked when the cells were incubated with house dust and anti-IgE, although, in some cases, the release induced by C. albicans was fairly marked. Basophils from patients under 30 years of age at onset were reactive to house dust and anti-IgE, while the cells from patients over 41 years of age at onset tended to be reactive only to C. albicans. Basophils from patients with low serum IgE levels were less reactive than the cells from patients with high levels of IgE to house dust and anti-IgE. C. albicans-induced release of histamine did not correlate with serum IgE levels.

A 47 year old woman with two isolated lumps in her right breast underwent an excisional biopsy and the histological findings of both lesions revealed fibroadenoma with an in situ lobular carcinoma. Patey's modified radical mastectomy was performed after which careful follow-up was continued. To date, a total 161 cases of carcinoma arising in a fibroadenoma have been reported in the world literature and a review of these literature is given following the case report.