C-type natriuretic peptide (CNP), a member of natriuretic peptide family, is mainly synthesized in the endothelium and central nervous system. But CNP is also involved in the growth and differentiation of other peripheral organs. Although we have reported the local synthesis and localization of CNP in the adult submandibular glands (SMG), it is not known that the expression and biological activity of CNP following the morphogenesis, differentiation and aging. This study aimed to examine the expression of CNP and its receptors in the developing and differentiating stages of mouse SMG, and the changes of biological activity of its receptors with aging. The SMG, obtained from 14, 16, 18 days-old embryos (E) and 1 day, 2 weeks, 1, 2, 12, and 24 month-old C57BL/6N mouse, were processed for RT-PCR, in situ hybridization, immunohistochemistry and cGMP assay. CNP was strongly expressed in the epithelial clusters of primitive SMG, which was maintained before birth but was markedly decreased after birth. CNP was localized in the intercalated duct and granular convoluted tubules of adult SMG, where NPRC was specifically expressed but NPRB was not. CNP mRNA was gradually decreased from E16 to 2 M but ANP mRNA was opposed. NPRB and NPRC were the same pattern of the expression of CNP but NPRA was weakly expressed. In addition, CNP mRNA was also expressed in the craniofacial tissues such as tooth germs, tongue, premaxilla and bone forming area in which NPRC was specifically expressed but NPRB was not. In the SMG of 2 M, the membrane of duct cells markedly produced cGMP by CNP whereas acini produced cGMP by ANP and BNP rather than CNP. The biological activity of cGMP production of SMG gradually decreased with age. cGMP production was dominant by CNP in SMG of 1M but was by ANP after 2M. These results shows that CNP may play roles both in the morphogenesis and differentiation via NPRC and in the maintenance of duct system via NPRB in the mouse SMG and that the biological activity of its receptors may decreased with aging.
Adult ; Aging* ; Animals ; Atrial Natriuretic Factor ; Central Nervous System ; Child, Preschool ; Embryonic Development* ; Embryonic Structures ; Endothelium ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Membranes ; Mice* ; Morphogenesis ; Natriuretic Peptide, C-Type* ; Parturition ; Pregnancy ; Receptors, Peptide* ; RNA, Messenger ; Submandibular Gland* ; Tongue ; Tooth Germ

A T-box transcription factor gene, Tbx1 is a principal candidate of the most frequent chromosomal deletion syndrome found in human, DiGeorge/velocardiofacial syndrome which is a complex developmental disorder associated with cardiac outflow tract abnormalities, mid facial dysmorphology, velopharyngeal insufficiency and submucosal cleft palate. We performed in situ hybridization against mouse embryo from E13.5 (bud stage) to E18.5 (late bell stage) in order to analyze the expression patterns of Tbx1 in the developing mouse first molar, a derivative of the first pharyngeal arch. Tbx1 transcripts were found in the dental lamina and its surrounding mesenchyme at E13.5 and in the dental organ except enamel knot at E14.5 (cap stage). Tbx1 was strongly expressed in the cervical loop and stratum intermedium but was weak in the dental papilla and dental follicle at E15.5 (early bell stage). At E18.5, Tbx1 was strongly expressed not only in the dental organ (bell stage) except stellate reticulum but also dental papilla and dental follicle adjacent to the inner dental epithelium. In conclusion, Tbx1 transcripts were specifically expressed both in the dental epithelium and surrounding mesenchyme of developing tooth from initiation to bell stage, which were the most similar with those of Sox9 but little different from those of Pitx2 and ectodin. These results strongly suggested that Tbx1 may play a role as a transcription factor regulating proliferation and differentiation of both dental epithelium and mesenchyme through the tooth development.
Animals ; Branchial Region ; Cleft Palate ; Dental Enamel ; Dental Papilla ; Dental Sac ; Embryonic Structures ; Epithelium ; Humans ; In Situ Hybridization ; Mesoderm ; Mice* ; Molar* ; Reticulum ; Tooth ; Transcription Factors ; Velopharyngeal Insufficiency

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection.
Acute Disease ; Blood Coagulation Factors/metabolism ; Child, Preschool ; Hepatitis A/blood/diagnosis/*etiology ; Humans ; Male ; Mycoplasma pneumoniae/pathogenicity ; Partial Thromboplastin Time ; Pneumonia, Mycoplasma/blood/*complications

MIN GLASSES is specially manufactured in order to enhance satisfaction of wearer and therefore increase the effectiveness of treatment of an amblyopia and a diplopia. One of the lens is specially grounded and coated to blur vision. Cosmetically, the eye appears to wear regular glasses through the blur lens. We prospectively studied 58 amblyopic children and 10 diplopic adults. Each patient was treated with MIN GLASSES for cosmetic problems. We checked linear visual acuity of pre- and post-treatment. Questionnaires were given to the patients and parents regarding cosmetic satisfaction with treatment. In amblyopic children. 44 patients(75.9%) showed visual acuity improvement of 1.61 +/- 1.50 lines by Han's visual acuity chart. Patient compliance was 87.9%(51 patients) with patient satisfaction based on a questionnaire response. Parents were 87.9%(51 parents) positive response. In diplopic adults, 10 patients(100%) were positive response with satisfaction and demonstrated to be free of symptom of diplopia. MIN GLASSES is effective in high compliance satisfaction of amblyopia and diplopia, and improvement of visual acuity of amblyopia.
Adult ; Amblyopia* ; Child ; Compliance ; Diplopia* ; Eyeglasses* ; Glass* ; Humans ; Parents ; Patient Compliance ; Patient Satisfaction ; Prospective Studies ; Surveys and Questionnaires ; Visual Acuity

BACKGROUND: Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis. METHODS: The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis. RESULTS: The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05). CONCLUSION: These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.
Animals ; Bleomycin ; Bronchiectasis ; Fibrosis ; Lung ; Lung Diseases ; Mice ; Pneumonia

BACKGROUND: Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis. METHODS: The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis. RESULTS: The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05). CONCLUSION: These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.
Animals ; Bleomycin ; Bronchiectasis ; Fibrosis ; Lung ; Lung Diseases ; Mice ; Pneumonia

BACKGROUND: Although the therapeutic mechanism of balneotherapy for atopic dermatitis has not been clarified, many atopic patients who visit thermomineral springs have shown clinical improvements. OBJECTIVE: This study was aimed to evaluate the immunomodulatory effect of thermomineral water balneotherapy on the atopic dermatitis murine model. METHODS: The oxazolone-induced atopic dermatitis murine model was used to evaluate the therapeutic effect of balneotherapy with Deokgu thermomineral water compared with distilled water. Histologic evaluation and confocal microscopic imaging were performed to analyze the lesional expression of cluster-of-differentiation (CD)4 and forkhead box p3 (Foxp3). Lesional mRNA expression of interleukin (IL) 33, thymic stromal lymphopoietin (TSLP), and Foxp3 was evaluated by real-time reverse transcription polymerase chain reaction. RESULTS: Compared with the distilled water bath group, confocal microscopic evaluation of CD4 and Foxp3 merged images showed increased expression of regulatory T cells in the thermomineral balneotherapy group. The lesional mRNA level of IL-33 showed a reduced trend in the thermomineral balneotherapy group, whereas the level of mRNA of Foxp3 was increased. TSLP showed a decreased trend in both distilled water and thermomineral water bath groups. There was a trend of reduced expression in lesional IL-33 mRNA but increased cell count of CD4+ Foxp3+ regulatory T cells in thermomineral balneotherapy compared with distilled water bath. CONCLUSION: Therefore, thermomineral balneotherapy can be an effective and safe adjuvant therapeutic option for atopic dermatitis.
Balneology* ; Baths ; Cell Count ; Dermatitis ; Dermatitis, Atopic* ; Humans ; Immunomodulation ; Interleukins ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; T-Lymphocytes, Regulatory ; Water*

OBJECTIVE: The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin. MATERIALS AND METHODS: We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results. RESULTS: One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 +/- 1.4 at 3 weeks to 0.9 +/- 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n = 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared. CONCLUSION: A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.
Animals ; Bleomycin ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred C57BL ; Observer Variation ; Pulmonary Fibrosis/chemically induced/*drug therapy/*radiography ; Thiazolidinediones/*therapeutic use ; *X-Ray Microtomography

BACKGROUND: We investigated the Janus kinase 2 (JAK2) mutation and its diagnostic value in patients suffering with non BCR/ABL myeloproliferative diseases (nMPD) or other reactive conditions. METHODS: We reviewed the clinical records of 83 patients who underwent bone marrow (BM) examinations with suspect of nMPD. The diagnoses of nMPD were made based on the WHO criteria since 2001 and the PVSG criteria before 2001. The JAK2 mutation was examined by PCR in 54 patients whose BM samples were available. RESULTS: The JAK2 mutation was detected in 25 patients (46%); 12 of 26 patients with essential thrombocythemia (ET), 9 of 12 patients with polycyhtemia vera (PV), one of 7 patients with chronic idiopathic myelofibrosis (CIM) and one patient with unclassifiable MPD. Additionally, JAK2 mutation was detected in each one patient with secondary polycythemia and reactive thrombocytosis. These two patients and two other patients among the JAK2 mutated ET did not meet the WHO PV criteria due to their initial low hemoglobin levels. These patients had liver cirrhosis and hypersplenism due to Budd-Chiari syndrome (1), gastrointestinal bleeding (1) or the initial hemoglobin level was slightly below the level as provided by the criteria, but the level showed a rising pattern despite cytoreductive therapy (2). With the results of the JAK2 mutation available, 4 patients' disease could be re-diagnosed as PV. Finally, the positive rate of the JAK2 mutation was 81% in PV, 48% in ET and 14% in CIM. The presence of JAK2 mutation closely correlated with PV (p=0.001), leukocytosis (p=0.001) and an increased cellularity of BM (p=0.024). CONCLUSIONS: The JAK2 mutation may help differentiate nMPD from secondary cytosis. Therefore, it should be incorporated into the guidelines for the nMPD work-up for making a more accurate diagnosis and administering proper treatment.
Retrospective Studies ; Proto-Oncogene Proteins c-bcr ; Polymerase Chain Reaction ; Myeloproliferative Disorders/*diagnosis/genetics/metabolism ; *Mutation ; Middle Aged ; Male ; Janus Kinase 2/*genetics ; Humans ; Genes, abl ; Female ; Diagnosis, Differential ; DNA/*genetics ; Biological Markers/metabolism ; Aged, 80 and over ; Aged ; Adult

PURPOSE: In this phase II study, the efficacy and safety of weekly paclitaxel concomitant with cisplatin and thoracic radiotherapy (TRT) was evaluated in patients with locally-advanced unresectable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) received TRT (63 Gy in 35 fractions over 7 weeks) with concurrent weekly cisplatin 20 mg/m2 and paclitaxel 40 mg/m2/week infused over 3 hours. In patients without evidence of disease progression, the administration of a further 2 cycles of consolidation chemotherapy, consisting of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, were planned after completion of the TRT. RESULTS: Between Feb 2000 and Dec 2002, 20 patients were entered into the study; 13 completed all 7 weeks of treatment (median 7.6 weeks; range 3.3 to 9.4). Seven out of 16 (43.8%) objective responses were observed, with 15 (75%) patients experiencing at least one episode of grade 3/4 toxicity. The main toxicities were moderate to severe neutropenia and gastrointestinal toxicity. CONCLUSION: The unsatisfactory response rate and the high incidence of grade 3/4 hematologic and non-hematologic toxicities, including 7 early discontinuations of treatment and exceeding the study stopping rules, prompted the early closure of the study. In view of the activity observed, the protocol was amended to protracted continuous infusion paclitaxel, cisplatin and concurrent TRT.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Consolidation Chemotherapy ; Disease Progression ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Pleural Effusion ; Radiotherapy