Therapy with nebulized beta2 agonists (procaterol) in asthmatic children: pulmonary function and plasma levels after inhalation]

BACKGROUND: Relationship between post administrative changes in plasma drug levels and bronchodilation remains unknown. In this study, we measured plasma levels of procaterol, a beta2-agonist, when being inhaled through nebulizers in children with bronchial asthma to examine relationship between improvement of pulmonary function and the plasma levels. METHOD: Six asthmatic children with the mean age of 9.8 years, inhaled 0.3 ml of 0.01% procaterol solution through a nebulizer. We examined changes in pulmonary function and plasma procaterol levels before and after inhalation. RESULTS: Procaterol was detected in the plasma 2 minutes after inhalation when it already rose to the maximum level, and kept the steady until showing a decline in 30 minutes. The measured highest value was 87.8+/-45.1 pg/ml. FEV 1.0 remarkably increased 2 minutes after inhalation and was maintained until 60 minutes after inhalation. Other lung function parameters also improved. There was no significant change in the heart rate, but serum potassium concentrations significantly dropped in all patients 60 minutes after inhalation. CONCLUSION: Plasma procaterol levels promptly rose to the peak at 2 minutes after inhalation and decreased 30 minutes later. Improvement of pulmonary function started promptly at minutes after inhalation and it became a peak 60 minutes later.     

Clinicopathological study of a hilar nodule in the livers of long-term survivors with biliary atresia

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill-defined nodule-like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long-term survivors, compared to the patients with nodule-like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well-preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule-like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well-preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less-affected hepatic tissues.     

Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span

Transgenic (Tg) mice overexpressing human thioredoxin (TRX), a small redox-active protein, were produced to investigate the role of the protein in a variety of stresses. Bone marrow cells from TRX-Tg mice were more resistant to ultraviolet C-induced cytocide compared with those from wild type (WT) C57BL/6 mice. TRX-Tg mice exhibited extended median and maximum life spans compared with WT mice. Telomerase activity in spleen tissues in TRX-Tg mice was higher than that in WT mice. These results suggest that overexpression of TRX results in resistance against oxidative stress and a possible extension of life span without apparent abnormality in mammals.     

Arpp,a new homolog of carp,is preferentially expressed in type 1 skeletal muscle fibers and is markedly induced by denervation

In this study, we isolated and characterized a murine counterpart of the human Arpp (hArpp) gene. Sequence analysis revealed that the murine Arpp (mArpp) gene is almost identical to the Ankrd2 gene, which has recently been isolated as a mouse gene induced in stretched skeletal muscle. The mArpp gene encodes a protein of 332 amino acids that contains four well-conserved ankyrin-repeat domains in the central portion of the protein. The amino acid sequence of mArpp protein (mArpp) is highly homologous to that of mouse cardiac-restricted ankyrin-repeat protein (Carp), which is proposed to be a putative genetic marker for cardiac hypertrophy. Immunohistochemical analysis revealed that mArpp is preferentially expressed in type 1 skeletal muscle fibers, and that mArpp is localized in both the nucleus and the sarcomeric I-band of muscle fibers, suggesting that Arpp may function as a nuclear and sarcomeric protein. Furthermore, mArpp was also expressed in neurons of the cerebellum and cerebrum, the islets of Langerhans in the pancreas, and the esophageal epithelium, suggesting that mArpp may play a functional physiologic role in brain, pancreas, and esophagus as well as in type 1 muscle fibers. Interestingly, although mArpp was localized in both nucleus and cytoplasm in neurons, its localization was restricted to nucleus in pancreas and esophagus, suggesting that intracellular localization of mArpp is regulated in a tissue-specific manner. Furthermore, we found that mArpp- and Carp-expression in skeletal muscle were markedly up-regulated after denervation. Although the elevated expression level of Carp was kept only for two weeks after denervation, that of Arpp was kept at least for 4 weeks, suggesting that mArpp and Carp may play distinct functional roles in denervated skeletal muscle.     

A Japanese male infant with the Weaver syndrome

A 15-month-old male infant who had pre- and postnatal overgrowth, accelerated bone maturation and characteristic facial appearance was described. Although a Japanese female with Weaver syndrome previously reported had slightly different clinical manifestations from others, our patient had typical clinical features of Weaver syndrome. We suggest that a genetic mutation of the syndrome may be the same in Japanese as other ethnic groups and that Weaver syndrome may be an autosomal dominant disorder with variable expressions.     

Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria

Hereditary coproporphyria (HCP) is an acute hepatic porphyriawith autosomal dominant inheritance, but with a variable degreeof clinical expression. Molecular cloning, sequencing and expressionof the defective gene for coproporphyrinogen oxidase (CPO) ina patient with HCP were carried out. Enzyme assays revealedthat CPO activity in EBV-transformed lymphoblastoid cells fromthe proband and one of her sisters was