Myeloid differentiation-2 is a potential biomarker for the amplification process of allergic airway sensitization in mice.

BACKGROUND: Allergic sensitization is a key step in the pathogenesis of asthma. However, little is known about the molecules that are critical regulators for establishing allergic sensitization of the airway. Thus, we conducted global gene expression profiling to identify candidate genes and signaling pathways involved in house dust mite (HDM)-induced allergic sensitization in the murine airway. METHODS: We sensitized and challenged mice with HDM or saline as a control through the airway on days 1 and 8. We evaluated eosinophilia in bronchoalveolar lavage fluid (BALF), airway inflammation, and mucus production on days 7 and 14. We extracted total RNA from lung tissues of HDM- and saline-sensitized mice on days 7 and 14. Microarray analyses were performed to identify up-regulated genes in the lungs of HDM-sensitized mice compared to the control mice. Data analyses were performed using GeneSpring software and gene networks were generated using Ingenuity Pathways Analysis (IPA). RESULTS: We identified 50 HDM-mediated, stepwise up-regulated genes in response to allergic sensitization and amplification of allergic airway inflammation. The highest expressed gene was myeloid differentiation-2 (MD-2), a lipopolysaccharide (LPS)-binding component of Toll-like receptor (TLR) 4 signaling complex. MD-2 protein was expressed in lung vascular endothelial cells and was increased in the serum of HDM-sensitized mice, but not in the control mice. CONCLUSIONS: Our data suggest MD-2 is a critical regulator of the establishment of allergic airway sensitization to HDM in mice. Serum MD-2 may represent a potential biomarker for the amplification of allergic sensitization and allergic inflammation.

[A pulmonary tumor embolism which mimicked pulmonary tumor thrombotic microangiopathy caused by uterine cervical cancer].

A 58-year-old woman presented with cough and dyspnea on exertion. A chest CT scan showed infiltrative cuneiform shadows in the peripheral lung fields. Pulmonary perfusion scintigraphy showed multiple nonsegmental defects. Histological analysis of the transbronchial lung biopsy specimens obtained from the right lower lobe showed tumor cell embolism and fibrocellular intimal proliferation, but no thrombus formation or recanalization in the small arteries. On the basis of these findings, we diagnosed pulmonary tumor embolism, not pulmonary tumor thrombotic microangiopathy (PTTM), because the pathological findings did not reveal either thrombus formation or recanalization, and the patient did not show hemodynamic effects such as hemolytic anemia, severe pulmonary hypertension, or disseminated intravascular coagulation. Systemic examinations revealed uterine cervical cancer. Her symptoms improved after the administration of chemotherapy and radiation therapy. Furthermore, the multiple nonsegmental defects observed on pulmonary perfusion scintigraphy disappeared. She was discharged, and her uterine cervical cancer has not recurred to date. Generally, a diagnosis of pulmonary tumor embolism and PTTM is difficult to establish in living patients. It is important that therapy is started before the disease progresses to PTTM, if pulmonary tumor embolism is diagnosed.

[Case of drug-induced pneumonia due to Saiko-karyuukotsu-boreitou].

We present a case of acute respiratory distress syndrome (ARDS) caused by allergic reactions to a herbal drug Saiko-karyuukotu-boreitou. A 57-year-old woman was admitted with a chief complaint of dry cough and dyspnea. She had been treated with Saiko-karyuukotsu-boreitou for postoperative pain and insomnia. Chest radiographs on admission showed diffuse infiltration shadows in both lungs. Chest CT scan showed diffuse ground glass opacities, consolidation and air bronchogram. Drug stimulation test was positive for Saiko-karyuukotu-boreitou. Based on the above findings, we diagnosed this case as Saiko-karyuukotu-boreitou-induced pneumonia. The patient recovered after discontinuation of Saiko-karyuukotu-boreitou. This is the fourth reported case of pneumonia induced by Saiko-karyuukotu-boreitou. We recommend careful observation when this medicine is prescribed.

Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.

Gitelman's syndrome is an autosomal recessive disorder marked by salt wasting and hypokalaemia resulting from loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter. Gitelman's syndrome is usually distinguished from Bartter's syndrome by the presence of both hypomagnesaemia and hypocalciuria. Although recent advances in molecular genetics may make it possible to both diagnose and differentiate these diseases, the phenotypes sometimes overlap. Here we report two sporadic cases of Gitelman's syndrome and two novel genotypes of SLC12A3. Patient 1 was a compound heterozygote with a known missense mutation, L849H, and a novel mutation, R852H in exon 22. Patient 2 was homozygous for the missense mutation L849H. To our knowledge, this is the first report of a patient homozygous for 849H. Interestingly, both patients were affected with autoimmune thyroid disease. Patient 1 was affected with Hashimoto's disease, and Patient 2 was affected with Graves' disease. The symptoms of Patient 2 were more serious than those of Patient 1. Although the patients both carried the 849H allele (Patient 1 as a heterozygote and Patient 2 as a homozygous), their clinical symptoms differed. The difference in the clinical features may have been due both to phenotypic differences and the fact that Gitelman's syndrome is a complicated disorder.