Yasuhei Odajima

Altered eosinophil levels as a result of viral infection in asthma exacerbation in childhood

Respiratory viral infection is known to be a significant cause of asthma exacerbation. Eosinophils have been considered to play an important role in the pathogenesis of virus‐induced asthma exacerbations. To determine how often asthma exacerbation is caused by virus infections and to examine the relationship between eosinophilia and asthma episode, we investigated 64 children who experienced asthma attacks between October 1999 and March 2000. We used rapid enzyme immunoassays to detect antigens of respiratory syncytial virus (RSV), influenza A virus, and adenovirus in nasopharyngeal secretions (NPS) of these children, and enumerated eosinophils in the blood and NPS. We detected RSV in 27% and influenza A virus in 17% of the patients. No adenovirus infection or RSV/influenza A co‐infection was detected. RSV‐infected children were younger (3.85 ± 0.83 years old) than influenza A virus‐infected patients (5.23 ± 1.34 years old). Eighty‐two per cent of patients in the RSV group and 36% of patients in the influenza A virus group had moderate‐to‐severe asthma episodes (p < 0.05). In RSV‐infected children, the eosinophil counts in NPS were higher in the ‘severe’ group, and younger patients had a greater number of eosinophils in their NPS than older patients (p < 0.05). These trends were not found in influenza A virus patients. In conclusion, our results indicate that, compared with influenza A virus‐induced asthma attacks, RSV infection had a higher probability of being associated with asthma exacerbation in infants and younger children and induced attacks of greater severity. The increase in the number of eosinophils in the NPS of RSV‐infected children may be responsible, in part, for these differences.

Airway Remodeling: A Comparison Between Fatal and Nonfatal Asthma

Background: Airway remodeling has been recently one of the main goals in asthma research because it has been implicated to influence airway behavior and evolution of asthma; hence, important in long‐term followup of asthmatic patients. Methods: Airways of fatal asthma (n = 3), non‐fatal asthma (n = 3) and control cases (n = 4) were studied using morphometry and immunohistochemical and H&E staining. Results: The basement membrane was thicker in the cartilaginous and membranous airways of fatal and non‐fatal asthma groups compared to the control group (p < 0.05). Smooth muscle shortening was greater in airways of fatal asthma cases while submucosal gland area and mucus plug occupying ratio were greater in fatal asthma large airways compared to the two other groups (p < 0.01). Increased intact and degranulated mast cells were observed in smooth muscle and in submucosal gland of fatal asthma airways (p < 0.01) and were associated with greater degree of smooth muscle shortening and larger submucosal gland area, respectively. Eosinophil and EG2 + cell infiltrations were greatest in lamina propria of airways of fatal asthma than in non‐fatal and control cases (p < 0.01), but were not associated with any airway structural change. Conclusion: Increased infiltration of eosinophils in the lamina propria and mast cells in smooth muscle and submucosal glands may have a role in airway remodeling of fatal asthma airways but needs further investigation. Moreover, mast cells in cartilaginous airways may participate in the regulation of smooth muscle tone and mucous gland secretion and hyperplasia.

IgE Binding to Raw and Boiled Shrimp Proteins in Atopic and Nonatopic Patients with Adverse Reactions to Shrimp

Background: Characterization of seafood allergens is important to understand the immune response to these allergens. Moreover, a detailed comparison between atopic and nonatopic patients with adverse reactions to shrimp has never been reported. Methods: Raw and boiled shrimp extracts were analyzed by immunoblotting using sera from 9 atopic and 7 nonatopic patients with a history of adverse reactions to shrimp, and 13 control subjects. Total IgE, specific IgE and skin prick tests (SPT) to shrimp were also investigated. Results: The level of specific IgE to shrimp was higher in atopic patients than nonatopic patients (p < 0.05). Symptoms, SPT results and major allergens involved were similar in atopic and nonatopic patients. The 16.5-kD protein had the highest frequency of IgE binding followed by the 40-kD protein in these patients. Other minor IgE-binding proteins were observed at the 20-, 22-, 54-, 72-, 129- and 140-kD regions. Patients who had binding to the 16.5-kD protein had either positive (25% raw/31% cooked) or negative (13% raw/cooked) CAP-FEIA-RAST, while patients who recognized the 40-kD protein all had positive (31% raw/19% cooked) CAP-FEIA-RAST. All control subjects had negative immunoblots for these two proteins. Conclusion: The 16.5-kD protein was the most frequent protein identified regardless of CAP-FEIA-RAST results, while the 40-kD protein was only present in patients with positive CAP-FEIA-RAST. Therefore, 16.5-kD protein may be an important allergen that is clinically relevant in both atopic and nonatopic patients with adverse reactions to shrimp even if it is not detected by the CAP-FEIA-RAST system.

How to Prevent Allergic Disease

We have investigated methods for decreasing the number of allergic patients and have produced the following data. We compared mothers’ total IgE levels and allergen-specific IgG and IgG4 levels in 72

Pharmacokinetic study of mizoribine in an adolescent with lupus nephritis

Mizoribine was previously isolated from the soil fungus Eupenicillum brefeldianum and has been shown to be an effective immunosuppressant. 1–6 In many studies, mizoribine has been used at a daily dosage of 2–5 mg/kg or 150–200 mg. 1,4,5 Our patient was given two different total daily dosages of mizoribine. The first total daily dosage was 250 mg and the second was 300 mg. We monitored the serum concentration of mizoribine. Although plasma concentration of mizoribine has been investigated in adult patients with lupus nephritis, 7 to our knowledge there are no reports about monitoring the serum concentration of mizoribine in a pediatric case of lupus nephritis.

Role of chemical mediators after antigen and exercise challenge in children with asthma

Changes in chemical mediators after antigen challenge and exercise challenge tests were studied in children with asthma. Chemical mediators studied after antigen challenge and exercise challenge included histamine, leukotrienes (LTB4, LTC4, and LTD4), and neutrophil chemotactic factor of anaphylaxis (NCA). The pharmacologic modification of immediate and late-phase reactions was evaluated for procaterol (beta 2-agonist), cromolyn sodium, and prednisolone. Histamine levels were noted to rise in patients who had a dual response of a mild to moderate nature, but did not change in patients who had severe asthma. During exercise challenge cromolyn sodium inhibited both immediate and late-phase reactions but also inhibited plasma generation of NCA. Prednisolone, on the other hand, did not affect immediate reactions, but blocked late-phase reactions to exercise and also decreased NCA generation. Procaterol inhibited the generation of LTD4 and also inhibited NCA when compared with placebo. Exercise challenge did not alter levels of plasma histamine or of LTB4 or LTC4.

Juvenile amyopathic dermatomyositis complicated by progressive interstitial pneumonia.

ACT may be the expression of an inborn error of metabolism with the features of an endoplasmic reticulum storage disease, such as seen in PiZZ AAT patients. In fact the pathological features of both deficiencies are very much alike. In the present case the presence of micronodular cirrhosis with PAS-positive diastase-resistant coarse globules in the hepatocytes, led initially to a misdiagnosis of cirrhosis associated with AAT deficiency. Nevertheless, immunohistochemistry showed no AAT immunoreactivity in the hepatocytes, but plasma level of AAT within normal limits. In contrast, although the plasma level was not measured, because the biochemical method was not available, immunohistochemistry with ACT antisera showed the intense reactivity, in the cytoplasmic granules of hepatocytes to be ACT. Ultrastructure could not be investigated but the presence of fluffy material in the dilated endoplasmic reticulum has been reported. The occurrence of cirrhosis in AAT and ACT deficiency could be explained by the fact that the hepatocytes are not capable of degrading the polymerized protein or by an increased synthesis of serpins, as might occur in some infections. In addition, the conformational instability can be accelerated by an increase in temperature as seen in AAT deficiency. We think that ACT deficiency was the cause of the cirrhosis in the present patient because the pathological features are consistent with this etiology, and because other causes have been ruled out on serologic and morphologic grounds. The patient, and his family, returned to Venezuela and has been lost to follow up so, no further studies could be done. It can be advocated that in children with chronic liver disease of unknown etiology, ACT plasma measurement or immunohistochemistry, with ACT antisera, on biopsy material must be performed for the diagnosis of ACT deficiency, especially in areas of high prevalence of this disorder. References

Case of insertion, inversion and deletion of chromosome 6

The infant boy involved in the present study was the only child born to Japanese healthy unrelated parents. The pregnancy was complicated by breech presentation, oligohydramnios and intrauterine growth retardation (IUGR). He had a left-sided hydronephrosis in his mother’s uterine. His mother took traditional Chinese medicine (Toki-inshi and Daio-kanzo-to) and oxatomide because of atopic dermatitis. At the 39th week of pregnancy, he was delivered by cesarean section because of fetal distress. His birthweight was 2592 g and his body length was 48.5 cm. Apgar scores were nine and 10 at 1 and 5 min, respectively. The infant required oxygen therapy for 13 days because of dyspnea. During the clinical course, the following manifestations were observed: developmental delay; hypotonia; auricular fistula; failure to thrive; hypertelorism; patent foramen ovale (PFO); patent ductus arteriosus (PDA); cleft lip; cleft palate; left hydronephrosis; sensorineural deafness; hyperuricemia; overlapping in the lower legs; bell-shaped thorax and dyspnea. He had recurrent episodes of respiratory tract infections with dyspnea. Patent foramen ovale and PDA were shown by echocardiogram. Left-sided hydronephrosis was shown by magnetic resonance imaging at the age of 5 months. According to the auditory brainstem response he had a sensorineural deafness. At the age of 5 months, he was admitted to our hospital for a cleft lip operation. However, the operation was postponed because he had an upper respiratory infection, which was treated with antibiotics and discharged once recovered. At the age of 7 months, he underwent a cleft lip operation. His bodyweight was 6590 g (–2.1 SD) and his body length was 66.0 cm (–1.5 SD). At the age of 8 months, he was admitted to our hospital for pneumonia and bronchial asthma. He was treated with theophylline for bronchial asthma. After 14 days of treatment, his uric acid became higher than 10 mg/dL. He was given allopurinol initially, with a dose of 20 mg daily and thereafter in doses of 40 mg daily. We also used sodium bicarbonate for his hyperuricemia. After 61 days of this treatment, his hyperuricemia improved. At the age of 11 months, his bodyweight was 6040 g (–3.3 SD) and body length was 66.4 cm (–3.1 SD). Anterior fontanel was 3.5 × 3.0 cm. Patellar tendon reflex was brisker than average. Scarf sign, head lag and loose shoulder were all positive. He could not achieve head control and he could not sit. He was discharged after recovery from pneumonia and bronchial asthma.