Prevalence rates and risk factors for allergic symptoms among inhabitants in rural districts

In order to determine the prevalence of allergic disorders and their association with agricultural factors, a total of 3,717 inhabitants of rural districts in Kumamoto Prefecture were ashed to fill out a questionnaire concerning their allergic status. The results obtained were as follows: One or more items of allergic symptoms were reported by 44% of the subjects. The prevalence rate of each symptom was 8% for respiratory organs, 5% for delayed type of respiratory disorders, 10% for nasal mucosa, 16% for eyes, 16% for urticaria-like derma and 26% for eczema-like derma. Twenty-one percent of the subjects had past histories of allergic diseases such as asthma (3%), nasal allergy (3%), urticaria (6%), contact dermatitis (9%) and so forth. These allergic conditions were seen to be more common among farmers than non-agricultural workers, and also among subjects with allergic constitution than those without such constitution. The highest (62%) prevalence of allergic symptoms was observed in farmers engaged in poultry raising, followed by those engaged in raising flowers (58%), tobacco (58%), cortinellus shiitake (55%), cucumber in plastic greenhouse (53%) and mandarin orange (53%). Among the symptomatic subjects, 12-38% of those with each symptom gave farm work as the direct causative factor for developing the corresponding symptom. Pesticide spraying was the most common agent among those factors.     

Hormone-dependency of human breast cancer in in vitro clonogenic assay

The in vitro clonogenic assay has been used to assess the biological effects of estradiol-17 beta (E 2) and an antiestrogen, tamoxifen (TAM) on human breast cancer, and the results were compared with the estrogen receptor status (ER). The sera used were treated with dextran-coated charcoal to avoid the modification effects of the endogenous hormones. There was a significant difference between ER (+) and ER (-) breast cancers in the incidence of cases in which the plating efficiency of cancers increased more than 50% over those of untreated control by adding 10(-8) M of E 2 (40.2% vs. 21.3%). TAM, 10(-6) M revealed a less than 50% colony formation of the control in 30.5% of ER (+) cancers, whereas only 13.0% of ER (-) cancers showed a response to TAM.     

Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat.

Glutathione transferase P (GST-P; glutathione transferase, EC 2.5.1.18) is known to be specifically expressed at high levels in precancerous lesions and in hepatocellular carcinomas from a very early phase of chemically induced hepatocarcinogenesis in the rat. The almost invariable occurrence of this phenotype in these lesions strongly suggests a mechanism by which GST-P gene is activated together with a crucial transforming gene of liver cells. To distinguish the two alternative possibilities--either the GST-P gene is coactivated with a closely located transforming gene by a cis mechanism or it is activated in trans by a common trans-acting factor--we carried out carcinogenesis experiments using transgenic rats harboring the bacterial chloramphenicol acetyltransferase reporter gene ligated to the upstream regulatory sequence of the GST-P gene. In each of three independent lines tested, liver foci and nodules produced by chemical carcinogens (Solt-Farber procedure) were found to express high levels of chloramphenicol acetyltransferase activity, indicating clearly that the GST-P gene is activated by a trans mechanism during hepatocarcinogenesis.     

Structural changes and cell viability of cultured epithelium after freezing storage

Numerous clinical reports have shown the utility of cultured epithelial grafting in the field of plastic and reconstructive surgery. Recently, freezing storage of the cultured epithelium has been tried and has successfully grafted after thawing. It is clinically convenient if it is possible for cultured epithelium to keep its normal structure and viability. However, few papers have described the structural changes in cultured epithelium after freezing storage. In the present study, the morphological changes and cell viability of cultured mucosal epithelial sheets after freezing were studied in comparison with cultured epidermal sheets. Furthermore, we discuss the effect of storage temperature and cryoprotectants.As a result, there were some structural changes such as vacuolar degeneration in the cultured mucosal sheets using dimethyl sulphoxide (DMSO) as a cryoprotectant. Such changes were more clearly observed at −80°C than at −196°C with DMSO. However, little morphological change was observed in both epithelial sheets cultured with glycerin. The cell viability analysed by flow cytometry showed that more than 62% of the cells kept their viability after freezing storage. These results suggest that the optimum conditions of freezing for cultured epithelium were −196°C storage by slow cooling methods with glycerin as a cryoprotectant.     

Responsiveness of human gastric tumors implanted in nude mice to clinically equivalent doses of various antitumor agents

To reproduce clinical effects of various antitumor agents in the human tumor/nude mouse model, we investigated the responsiveness of 11 lines of human gastric tumor xenografts to doses of the agents pharmacokinetically equivalent to the respective clinical doses, which we designated the "rational dose" (RD). We found that the response rates to mitomycin C, 3-[(4-amino-2-methyl-5-pyrimidinyl]methyl-1-[2-chloroethyl]-1- nitrosourea (ACNU), adriamycin, 5-fluorouracil were 18%, and that to vinblastine was 30%; on the other hand, those to vincristine, methotrexate, and cyclophosphamide were poor. In contrast, in our previous study using the maximum tolerated doses, response rates to mitomycin C, ACNU, and vinblastine were as high as 64-82%, and those to adriamycin and 5-fluorouracil were 18%. When these results were compared with the clinical response rates of gastric tumors, as a whole, the results with RD's exhibited much better coincidence with the clinical data in terms of relative therapeutic potency, indicating the validity of the use of clinically equivalent doses instead of maximum tolerated doses in the human tumor model.     

Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea-pigs in vivo

BACKGROUND: Indoor formaldehyde (FA) might worsen allergies and be an underlying factor for the increasing incidence and severity of asthma; the exact mechanism, however, remains unclear. OBJECTIVE: The present study examined the effects of repeated exposure to FA on methacholine- and antigen-induced bronchoconstriction in guinea-pigs in vivo. METHODS: First, non-sensitized guinea-pigs were transnasally treated with 0.1 or 1.0% FA or saline three times a week for 6 weeks, and increasing concentrations of methacholine (50, 100, and 200 microg/mL) were inhaled at 5-min intervals. Second, guinea-pigs pre-treated with transnasal administration of FA or saline using the same protocol were passively sensitized with anti-ovalbumin (OA) serum 7 days before antigen challenge. Third, guinea-pigs were actively sensitized with OA and pre-treated with transnasal administration of FA or saline using the same protocol. The lateral pressure of the tracheal tube (Pao) was measured under anesthesia and artificial ventilation. RESULTS: The antigen-induced increase in Pao in actively sensitized guinea-pigs was significantly potentiated by FA exposure in a dose-dependent manner. The dose-response curve of the methacholine-induced increase in Pao in non-sensitized guinea-pigs or of the antigen-induced increase in Pao in passively sensitized guinea-pigs was not altered by FA exposure. Transnasal administration of FA significantly increased the serum anti-OA homocytotropic antibody titre (IgG) as measured by the passive cutaneous anaphylaxis reaction in actively sensitized guinea-pigs. CONCLUSION: The results suggest that repeated exposure to FA worsens allergic bronchoconstriction through enhancing antigen sensitization.     

Relationship between HLA-D and in vitro and in vivo responsiveness to Candida allergen.

In vitro reaction to Candida allergen was studied in 100 normal healthy Japanese and related to HLA. A significant association was found between the low responder group (< 7,000 c.p.m.) and HLA-B15 and the high responder group (> 7,000 c.p.m.) and HLA-B7, as well as Dwl. Four HLA-D homozygote cells of types HLA-Dwl and DHO, were tested; these fitted in the high responder group. HLA-DYT and DEn fitted into the low responder group. Responsiveness to Candida allergen corresponded to skin test (r = 0.884, P < 0.01). From these results, in vitro lymphocyte reaction to Candida allergen and skin tests showed close correlation and an association with HLA antigens, HLA-D in particular.     

Disease associations and altered immune function in CD45 138G variant carriers

The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.