Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase.

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.

IL-4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: two-locus haplotypes are more informative than individual SNPs.

The IL-4RA locus encodes for the alpha chain of the IL-4 receptor, and is both a functional and positional candidate gene for atopy and allergic disease. Recently Ober et al. have shown that the study of haplotypes at multiple loci in the IL-4RA gene could be more informative than the separate study of single nucleotide polymorphisms (SNPs). One hundred and fifty subjects affected by atopic asthma and 150 healthy control subjects were studied in the English population (Oxford district). Subjects and controls were genotyped for the Ile50Val, Ser478Pro and Gln551Arg polymorphism of the IL-4 receptor alpha chain. The distribution of haplotypes 50-478 shows a highly significant association with IgE levels. In particular, the haplotype Val50/Pro478 is much less frequent in subjects with IgE levels > 100 U mL-1 than in those with IgE levels < 100 U mL-1. Furthermore, the distribution of haplotype 50-551 shows a weak association with IgE levels that is lacking for 478-551 haplotypes. A lower frequency of the Val50/Pro478 haplotype is also observed among asthmatic subjects as compared to healthy controls. With regard to individual SNPs (50 478 and 551), no significant association has been observed with IgE levels or with asthma, thus confirming the higher informative value of the haplotype analysis as compared to separate study on SNPs.

Cost-benefit analysis methods for assessing air pollution control programs in urban environments-A review.

The most common method of evaluating beneficial impacts of environmental policies is cost-benefit analysis (CBA). In the present review, CBA methods for air pollution impacts are reviewed. Three types of air pollution effects are identified, including health, productivity, and amenity. Market valuation, stated preference methods, and revealed preference methods are identified for valuing benefits. Three types of costs are deseribed, including private sector costs, societal costs, and governmental regulatory costs. A benefits valuation approach based on Freeman's principals is described. A costs valuation approach based on U.S. Environmental Protection Agency and Dixon et al. principals is deseribed. Limitations associated with estimates of benefits and costs are summarized. Input assumptions and results are compared for several existing air pollution control analyses. The importance of CBA in environmental policy studies is discussed. Our conceptual approaches should be useful in analyses of urban air pollution impacts and air pollution prevention policies.

Comparative study of the antitumor effect of two types of murine recombinant interferons, (beta) and (gamma), against B16-F10 melanoma.

A comparative study of the antitumor effect of murine recombinant interferon(beta) less than Mu-rIFN(beta) greater than and murine recombinant interferon(gamma) less than Mu-rIFN(gamma) greater on B16-F10 melanoma was conducted. Administration of Mu-rIFN(gamma) i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN(beta) both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN(gamma) demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN(gamma) at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN(beta) hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN(beta) than Mu-rIFN(gamma), whereas Mu-rIFN(gamma) enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(beta). Injection of Mu-rIFN(gamma) i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(gamma). From these results, it is suggested that the inhibitory effect of Mu-rIFN(gamma) on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN(beta).

Prognostic factors in non-small cell lung cancer: multiregression analysis in the National Cancer Center Hospital (Japan).

A total of 190 patients with unresectable non-small cell lung cancer (NSCLC) were analyzed retrospectively using eight pretreatment and three treatment-related prognostic factors in terms of influence on survival. All the patients received chemotherapy with or without chest irradiation, according to the protocol of phase II or phase III trials of the National Cancer Center Hospital Tokyo between April 1980 and December 1985. The eight pretreatment factors selected were performance status, sex, stage, age, histology, and metastasis to brain, bone or, liver. Three treatment-related factors were radiation therapy to the primary site, response to chemotherapy, and treatment period, before or after clinical administration of cis-diamminedichloroplatinum (II) (CDDP). Of the 190 patients, 71 (37.4%) were alive for more than 1 year, but only 17 patients (8.9%) survived 2 years after the initiation of chemotherapy. By univariate analysis, performance status 0-1, female, no metastasis to bone or liver, response to chemotherapy, and treatment period after CDDP were considered to be favorable prognostic factors. By multiregression analysis, performance status, sex, and treatment period after CDDP proved to be important factors for long-term survival. Consideration of these prognostic factors could enable the results of chemotherapy to be more accurately evaluated, and stratification of patients with advanced NSCLC based on performance status and sex before entry into a randomized controlled trial is recommended.

A case of adiposis dolorosa: lipid metabolism and hormone secretion.

The present report describes a 53-year-old non-obese man with adiposis dolorosa whose pain was dramatically relieved by the intravenous injection of lidocaine. The patient showed a paradoxical response of growth hormone to thyrotropin-releasing hormone. In addition, in-vitro studies on adipose tissue metabolism revealed the reduced glucose conversion to neutral glycerides in painful adipose tissue. These abnormalities may be related in some ways to the pathogenesis of this disorder.

Effect of TEI-4120 (3-benzoyl-N-beta-ethoxyisopropyl-2-methlindole) on carrageenan induced disseminated intravascular coagulation (DIC) in rats.

In order to evaluate TEI-4120 (3-benzoyl-N-beta-ethoxyisopropyl-2-methylindole), as a possible therapheutic compound to disseminated intravascular coagulation (DIC), DIC model in rats was induced by the treatment of lambda-carrageenan according to the method of Sugiyama et al. with minor modification. Two hours after intraperitoneal injection of lambda-carrageenan, plasma fibrinogen decreased and platelet count, prothrombin time, serial thrombin time and plasma TXB2 prolonged or increased. By use of this model, the activities of TEI-4120, new antithrombotic compound, was evaluated compared with three other compounds, aspirin, warfarin and heparin. As a result, TEI-4120 is effective in this model. Combination therapy of TEI-4120 and warfarin is more effective than single administration of TEI-4120. The effect of combination therapy of TEI-4120 and warfarin is consistent with that of heparin. The above result suggests that TEI-4120 seems to be a promising compound to the therapy of DIC.