The CC16 A38G polymorphism is associated with the development of asthma in children with allergic rhinitis.

BACKGROUND: Although asthma and allergic rhinitis (AR) are considered to be one syndrome, many questions remain unanswered. Why do some AR patients develop asthma but others do not, and which factors play a role in the development of asthma that have so far not been clearly elucidated. OBJECTIVE: We hypothesize that children with AR who have the Clara cell secretory protein (CC16, secretoglobin 1A1) 38A/38A genotype (rs3741240) have an increased likelihood of developing asthma. METHODS: The study sample included 117 children, with AR, but no asthma diagnosed within the following 5 years, as the control group. Cases group (n=202) included age- and gender-matched children with AR first, and asthma developed 3-5 years later, as the study group. The CC16 genotype was determined by PCR and Sau96I restriction digestion of PCR products. The serum CC16 levels were measured by ELISA. Total serum IgE, allergen specific IgE, eosinophil count and pulmonary function were also measured. RESULTS: In children with rhinitis who develop asthma, the frequencies of the AA genotype were significantly higher than those who did not develop asthma [odds ratio (OR)=2.527; 95% confidence interval (CI)=1.571-4.065; P<0.01]. Serum CC16 levels in the children with rhinitis who develop asthma and carry the AA genotype were significantly lower than those who carry the non-AA genotype and those who did not develop asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that CC16 38A/38A genotype plays a role in the development of early asthma in children with AR. Early identification of rhinitis children at risk may assist in designing preventative approach to asthma development.

Paclitaxel induces apoptosis via caspase-3 activation in human osteogenic sarcoma cells (U-2 OS).

Paclitaxel has been found to exhibit cytotoxic and antitumor activity. There is little information regarding the mechanisms of apoptotic-inducing effect of paclitaxel on human osteogenic sarcoma U-2 OS cells. Several key regulatory proteins are involved in the initiation of apoptosis. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis. We examined the effect of paclitaxel on the cell cycle arrest and apoptosis in U-2 OS cells using flow cytometric analysis and Western blotting. We also measured the inhibition of paclitaxel-induced apoptosis and the caspase-3 activity by the broad-spectrum caspase inhibitor z-VAD-fmk on U-2 OS cells. The increased levels of casapse-3 were also confirmed by cDNA microarray. Our observations were: (1) paclitaxel treatment resulted in G2/M-cycle arrest in U-2 OS cells; (2) time and dose dependent apoptosis of U-2 OS cells was induced by paclitaxel; (3) in U-2 OS cells, z-VAD-fmk blocked the paclitaxel-induced apoptosis and caspase-3 activation. These results suggest that paclitaxel-induced G2/M-cycle arrest of the G2/M phase and apoptosis via a caspase-3 pathway in U-2 OS cells.

Oral administration of paclitaxel affects the distribution and metabolism of 2-aminofluorene in various tissues of Sprague-Dawley rats.

To evaluate the question of whether or not paclitaxel affects the distribution and metabolism of chemical carcinogens such as 2-aminofluorene (AF) on Sprague-Dawley rats were examined. The AF, acetylated AF and AF metabolites were determined and examined by using high performance liquid chromatography. After having received AF only, AF with paclitaxel at the same time and paclitaxel pretreated for 24 h then treated with AF for 24 h, urine, stool and tissues such as liver, kidneys, stomach, colon, bladder and blood were collected and assayed for AF and its metabolites. Compared to the control group, paclitaxel caused an increase of the metabolites excreted in urine and stool. The major metabolite excreted in urine and stool was 9-OH-AAF. The liver is the major metabolism center and the major residual metabolite of AF in the liver was also 9-OH-AAF.

Eosinophilic gastroenteritis in children-report of one case.

Eosinophilic gastroenteritis is rare in pediatric patients. The three main manifestations, defined by Klein et al. in 1970, were (a) predominant mucosal, (b) predominant muscular-layer, and (c) predominant subserosal disease. The predominant subserosal type is the rarest of the three. We report on a 43-month-old boy who, on admission, suffered from recurrent abdominal pain, vomiting and diarrhea for one week, with ascites and pleural effusion noted. The white blood cell (WBC) count of ascites fluid was 8,000/mm3, with a differential count of 99% eosinophils. The peripheral WBC count was 44,000/mm3, with 78% eosinophils. Three days after diagnosis, ascites, pleural effusion and other gastrointestinal symptoms were gradually relieved using steroid therapy, with the peripheral eosinophil count returning to normal. The steroid therapy was discontinued after two months with tapering dose. The boy was in good health with no recurrence of symptoms in a follow-up conducted after one year.

Household distribution of house dust mite in central Taiwan.

House dust mite (HDM) is a common inhalant allergen which can precipitate atopic disease episodes including asthma and allergic rhinitis. However, the relationship between HDM and asthma in subtropical regions of Asia, which may be affected by differences in climate and environmental variables, has not been widely studied. To assess this relation in the subtropical region of central Taiwan, we collected HDM samples from the houses of eight asthmatic patients as well as four normal subjects over a 1-year period. HDMs were collected by vacuum from the following four areas: living room floor, sofa, the top surface of child's mattress and bedroom floor. The mite concentrations, site distribution, seasonal variation, individual species and correlation with asthmatic attacks were studied. The HDM concentration had a seasonal variation, with the highest concentrations noted from July to November with gradually decrease from December to June. Among the four areas of collection, the highest concentration of mites was found on the child's mattress (p < 0.05). Dermatophagoides pteronyssinus was the dominant species (77%) and Dermatophagoides farinae was the second (13%). Our data showed that: 1. The highest concentrations of HDM occurred during the period from July to November. 2. The child's mattress was the household region with the highest percentage of HDM and thus should be considered of great concern as a likely source of the exacerbation of asthma. 3. D. pteronyssinus was the dominant species.

Allergic diseases in preschool children in Taichung City.

The occurrence of allergic diseases in preschool children was studied on the basis of a questionnaire sent to the parents of 5,408 kindergarten students, 3 to 6 years of age, in Taichung City. The overall response rate was 81% and included 2311 (52.8%) boys and 2062 (47.2%) girls. Allergic diseases had been recognized in 34.6% of the children. The cumulative (lifetime) prevalence of bronchial asthma (BA), allergic rhinitis (AR), atopic eczema (AE), and urticaria were 9.4%, 26.4%, 6.6% and 6.8%, respectively. The current (past 12 months) prevalence of BA, AR, and AE was 6.7%, 14.8%, and 3.5%, respectively. BA and AR occurred more frequently in boys than in girls (P < 0.001); no significant difference was found between boys and girls in AE (P = 0.328). There were statistically significant relationships between positive family history and BA, AR and AE (P < 0.001). In conclusion, allergic diseases constitutes an important health problem for pre-school students in Taichung City.

Renal function in neonatal hyperbilirubinemia.

A total of 75 jaundiced infants with gestational ages ranging from 37 to 42 weeks were studied during the first 10 days of age to evaluate renal function by measuring endogenous creatinine clearance (Ccr), fractional excretion of N-acetyl-beta-D-glucosaminidase (NAG) to creatinine, fractional excretion of sodium (FENa) and urine osmolality. All jaundiced infants were divided into two groups. Group 1 infants (n = 35) had total serum bilirubin levels ranging between 21 and 39.6 mg/dl (mean 27.2). Exchange transfusions were performed in all group 1 infants at the time of the initial study. Group 2 infants (n = 40), whose total serum bilirubin levels ranged between 12.3 and 20 mg/dl (mean 16.4), received phototherapy, except for 2. Conjugated bilirubin levels were less than 1.0 mg/dl in all these infants. Results were compared with 25 untreated control infants with corresponding gestational and postnatal ages. Follow-up studies were done in 27 of the 35 group 1 infants and in 32 of the 40 group 2 infants prior to hospital discharge, when total serum bilirubin levels had decreased to less than 10 mg/dl. Ccr, fractional excretion of NAG to creatinine, FENa and urine osmolality of group 1 infants were statistically significantly different when compared to those of group 2 and the control infants. The measured parameters in the post-treatment follow-up study of group 1 infants returned to near-normal levels when total serum bilirubin levels became normal. However, no significant differences were seen between group 2 and the control infants in any of the measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal calcification in very low birth weight infants.

Between January 1990 and December 1991, serial real-time ultrasound examinations and analyses of urine were performed on a total of 50 infants with birth weights less than 1,500 g to assess the incidence of renal calcification. Five infants (10%) developed renal calcification at a mean age of 48.8 +/- 14.1 days. These 5 infants with renal calcification had significantly shorter gestations (28.2 +/- 0.8 vs. 30.1 +/- 1.7 weeks, p < 0.0005) and lower birth weights (934 +/- 45 vs. 1,311 +/- 188 g, p < 0.0005) when compared with infants without renal calcification. None of the affected infants were treated with furosemide. Affected infants had a mean urine volume of 85.8 +/- 11.3 ml/kg/24 h, mean urine calcium level of 5.07 +/- 1.18 mg/kg/24 h, mean urine calcium to creatinine (mg/mg) ratio of 0.67 +/- 0.09, and a mean urine N-acetyl-beta-D-glucosaminidase (NAG) to creatinine (U/g) ratio of 259 +/- 133. Urinalyses showed that affected infants had significantly higher urine pH values and hematuria. Alkaline phosphatase concentrations and initial parathyroid hormone levels were not different among the two groups. In summary, renal calcification occurred in 10% of very low birth weight infants and multiple risk factors seem to be contributory. The smaller, sicker and more immature infants appear to have increased risk for developing renal calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

Engagement of CD14 on human monocytes terminates T cell proliferation by delivering a negative signal to T cells.

We have recently shown that engagement of the human monocytic Ag CD14 by murine mAb induces lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion. To determine whether CD14 plays a role in monocyte-T cell interactions, we tested the effect of anti-CD14 mAb on the proliferation of human T cells. Our results show that anti-CD14 mAb strongly inhibited T cell proliferation induced by Ag, anti-CD3 mAb, and mitogenic lectins. Inhibition by anti-CD14 mAb was epitope-dependent and required physical contact between monocytes and T cells. CD14 engagement did not affect IL-2R expression or IL-2 synthesis but induced a state of unresponsiveness that was not IL-2 specific; proliferation of anti-CD3-activated T cell blasts in response to both IL-2 and IL-4 was abrogated by addition of monocytes preincubated with anti-CD14 mAb. Inhibition of T cell proliferation after engagement of CD14 on monocytes was likely to result from delivery of a negative signal to T cells, rather than from disruption of a costimulatory monocyte-derived signal, because incubation of monocytes with anti-CD14 mAb also inhibited monocyte-independent T cell proliferation induced by PMA and ionophore. These results, together, point to a role of CD14 in the monocyte-dependent regulation of T cell proliferation.

Changes of allergen-specific antibodies, circulating immune complexes and restoration of polymorphonuclear leukocyte function after hyposensitization.

To explore the working mechanism(s) and the safety of long-term hyposensitization (HS) with house dust (HD), a series of studies were undertaken on 30 newly diagnosed and 30 hyposensitized asthmatic children. Twenty age- and sex-matched school children were included as control. The results showed: (1) HS was able to decrease the total serum IgE and increase the production of allergen-specific IgG blocking antibody, however, the allergen-specific IgE antibody remained nearly the same after HS for a couple of years, (2) Normal controls had allergen-specific IgG antibody but no IgE antibody, (3) Circulating immune complex concentration in the treated group did not differ significantly from the untreated group, (4) HS was able to suppress in vivo and in vitro histamine production and restore polymorphonuclear leukocyte (PMN) function in terms of Fc gamma R expression. These results suggest that HS is a specific and safe treatment, and provide solid rationale for its use in the treatment of respiratory allergic disease.

Defective monokine production and decreased responsiveness of polymorphonuclear leukocytes to recombinant interleukin-1 in asthmatic patients.

Augmented IgE production and increased infections are often seen in allergic patients. As monocytes (MN) and polymorphonuclear leukocytes (PMN) are involved in both immune regulation and inflammatory reaction, MN function in terms of monokine production stimulated with lipopolysaccharide (MN supernatant; MN-sup) and its biological activity and the response of PMN to MN-sup and recombinant interleukin-1 (rIL-1) regarding chemotactic activity and expression of IgG Fc receptor (FcR) were studied in 26 normal children and 28 new and 22 hyposensitized (HS) asthmatic children. The results showed the following. There was no difference in IL-1 production, as assayed by thymocyte proliferation, among the three groups. All MN-sup from the three groups could enhance IL-2 production, but that of new patients was less efficient. In the absence of PWM, MN-sup of new patients greatly augmented the production of IgG, IgA, IgM, and IgE, but that of HS patients could enhance only IgE synthesis. MN-sup of patients enhanced less efficiently the chemotactic activity and FcR expression of PMN from healthy volunteers, and PMN from asthmatics responded much less vigorously to rIL-1 regarding the above-mentioned functions. The number of PMN with membrane IL-1 was much lower in allergic patients. Thus the abnormal MN and PMN functions may be used to explain partly the augmented IgE production and increased infections in allergic patients.

Immunological changes after hyposensitization in house-dust-sensitive asthmatic children: a review.

Patients with allergic diseases are characterized by the presence of elevated total serum IgE and specific IgE antibodies against a variety of environmental allergens. To explore the causes for augmented IgE antibody production and the working mechanisms of hyposensitization (HS), a series of studies has been conducted on house-dust-sensitive, newly diagnosed, and hyposensitized asthmatic children and normals. The specific IgE and IgG antibodies were measured by radioallergosorbent test; the lymphoproliferative capability was measured by 3H-thymidine incorporation; the allergen-specific suppressor activity was determined by the extent of house-dust-activated, interleukin-2 (IL-2)-expanded lymphocytes to suppress the allergen-induced proliferation of autologous mononuclear cells (MNC); and IL-2 was produced by stimulating MNC with allergen or phytohemagglutinin (PHA) and quantitated by its capability to support the proliferation of mouse IL-2-dependent cytotoxic T-cell line. The results showed: 1) HS was effective in 90% of patients in terms of decreased attacks and medication taken; 2) the patients were defective in suppressor T-cell function for IgE production; 3) HS was able to restore the regulatory T-cell function and increase the production of IgG-blocking antibody; and 4) IL-2 production may be used as an indicator for initiation and discontinuation of HS. Therefore, hyposensitization is an effective and specific treatment for allergic bronchial asthma and can partially correct an immunoregulatory aberration in atopic individuals.