[The expression of P19ink4d in the pathogenesis and development of hearing loss].

Objective: This study aimed to investigate the P19ink4d expression in cochlea of mice model with noise induced hearing loss and the role of P19ink4d in the degeneration of inner ear cells. It also searched for P19ink4d gene alterations in patients with profound sensorineural deafness.Method: CBA/J mice were exposed to broad band noise at 101 dB SPL for 2 hours, auditory brainstem response (ABR) were examined to confirm noise lead to the permanent threshold shift. Immunohistochemical staining, Western blotting, and real-time polymerase chain reaction (PCR) were performed on cochlear tissues, to elucidate changes in P19ink4d expression in mice after noise exposure. For clinical evaluation, 400 children from unrelated families with severe or profound sensorineural hearing loss (SNHL) were recruited, genomic DNA was obtained from the patients and was subjected to DNA microarray to screen mutations in 4 most common genes. The sample that carried none of the common mutant alleles were subjected to PCR and sequenced to detect mutations in P19ink4d gene.Result: The ABR threshold shift of mice in the experimental group significantly increased after noise exposure and was higher than that in the null-noise group. The ABR of 1 day post noise was least among experimental groups and there is no statistical different between ABR of 7 days and 14 days post noise. The missing of outer hair cells occurred after noise exposure, while the inner hair cells hardly miss. It was found that the P19ink4d expression increased significantly in the inner ear cells 3 hours after noise exposure, then recovered in 24 hours. Western blot indicated that the amount of P19ink4d increased transitorily 3-6 h after the noise. However, no mutation existed within the coding exons of P19ink4d in the patients with profound sensorineural deafness.Conclusion: The results support the concept that P19ink4d may play an important role in the pathogenesis and development of noise induced hearing loss.

[Primary Ewing's sarcoma of the temporal bone: a rare case].

SummaryEwing's sarcoma is a malignant, round cell tumor arising from the bones and primarily affecting children and adolescent. Involvement of the skull bones is rarely reported, constituting 1%-6% of the total Ewing's sarcoma cases. We describe a 33 years old male patient having Ewing sarcoma of the mastoid and petrous parts of temporal bone, whose clinical presentation mimicked mastoiditis with facial nerve palsy. We discuss the clinical and therapeutic course of an extensive primary Ewing sarcoma of the temporal bone and review this entity's literature in detail. The etiopathology of an acute peripheral facial palsy is often hard to identify. If the facial weakness starts together with symptoms suggesting an inflammatory process, the differential diagnosis may be focused first on diseases like herpes zoster oticus and a severe course of acute purulent otitis media. As an uncommon tumor of the temporal bone, physicians should consider Ewing's sarcoma in the differential diagnosis of children and adolescents who present with facial nerve paralysis. And in the case of ambiguous clinical findings, a surgical exposure of the middle ear is recommended.

[Analysis of tinnitus with sudden deafness].

Objective:To explore the pathogenesis of tinnitus.Method:Retrospective analysis of 192 patients with sudden deafness was done with the characteristics.Charactier of tinnitus and the factors that may affect tinnitus.Result:The intense of tinnitus is related with sex,χ²=14.704,P<0.01,and with age increased,the difference was more significant.The intense of tinnitus has not significant difference between age group with 45 years old(χ² =6.515,P>0.05) and the classification of sudden deafness and the degree of hearing loss(χ²=7.783,P>0.05,χ²=17.374,P>0.05).Conclusion:Tinnitus was the protection mechanism of the body,and the intensity was irrelevant to hearing loss.On one hand,there may be different modulate systems between different individual,on the other hand,women over 45 years old were more suffered from the severe tinnitus.

Prevention of autoantibody formation and prolonged survival in New Zealand Black/New Zealand White F1 mice with an ancient Chinese herb, Ganoderma tsugae.

For centuries, Chinese medicine has regarded Ganoderma, a fungus (Myceteae, Amastigomycota, Busidomycetes, Aphyllophorales, Polyporaceae, Ganoderma) also known as 'Ling Zhi' in Mandarin, as a premium remedy for many diseases. Until now, no convincing data regarding its therapeutic effects in vivo on autoimmune diseases have been demonstrated. In this study, a controlled protocol was conducted in which New Zealand Black/White F1 mice were fed standard chow with prednisolone (0.5 mg/kg/day) or Ganoderma tsugae extract, commencing at 2 months of age. It was found that the F1 mice responded well to Ling Zhi extract. Ling Zhi improved the survival rate of lupus mice, decreased the amount of proteinuria, decreased serum levels of anti-dsDNA autoantibody, and showed evidence of decreased perivascular and parenchyma mononuclear cell infiltration in vital organs.

Fullerenes as a new class of radioprotectors.

PURPOSE: To evaluate the radioprotective activity of C3, a regioisomer of water-soluble carboxyfullerene and a potent free radical scavenger, on both normal and tumour cells. MATERIALS AND METHODS: The murine committed bone-marrow stem cells for both granulocytes and monocytes (GM-CFC) were used to represent normal cells. For tumour cells, murine Ehrlich ascites tumour cells grown in regular tissue culture (EAT-T) and in the peritoneal cavity of CD1 mice (EAT-PC) and human HeLa cells were used. Cells were preexposed to varying concentrations (1-100 microg/ml) of C3 at 37 degrees C for 30 min before they were irradiated. Clonogenic assays were used to determine survival. The protection factor (PF), defined as the ratio of survival with and without C3, was then determined. RESULTS: C3 protected GM-CFC in a concentration-dependent manner up to 50 microg/ml, and no additional protection was seen at 100 microg/ml. The PF was 1.77 when bone-marrow cells were pre-exposed to 50 microg/ml of C3 before they were irradiated with 2 Gy. The value of PF increased to 2.38 when 4 Gy was used. In sharp contrast, C3 exerted less radioprotective effect on tumour cells. The PF values were 1.07, 1.43 and 1.07 for EAT-T, EAT-PC, and HeLa cells, respectively, when 2 Gy was given in the presence of 50 microg/ml of C3. These values increased to 1.40, 1.75 and 1.27, respectively, when 4Gy was given. The dose-modifying factors at 10% survival were 1.37 and 1.15 for GM-CFC and EAT-PC, respectively. CONCLUSION: C3 exhibits a radioprotective effect on a class of normal haemopoietic progenitor cells. It also protects tumour cells, but to a lesser degree. It appears that C3 and other water-soluble fullerenes have a potential to be a new class of cytoprotectors.

Sauropus androgynus-constrictive obliterative bronchitis/bronchiolitis--histopathological study of pneumonectomy and biopsy specimens with emphasis on the inflammatory process and disease progression.

AIMS: The histopathology of the Sauropus androgynus (SA)-constrictive bronchiolitis obliterans (BO) is still controversial. A recent report using pneumonectomy specimens showed that the major histopathology was obliterative arteriopathy with segmental necrosis of small bronchi instead of constrictive BO as previously described. METHODS AND RESULTS: We analysed semiquantitatively and immunohistochemically the histopathology of one pneumonectomy and four biopsies specimens of SA-associated lung disease. We found a significant number of constrictive and obliterative bronchioles 1 mm or less in diameter and segmental inflammatory destruction with complete luminal obliteration of the bronchi less than 3 mm in diameter in the pneumonectomy specimen (37% and 25%, respectively). Fibromuscular intimal sclerosis of the bronchial arteries was identified in 15% of the bronchi 4 mm or less in diameter. The inflammation in these airways was composed predominantly of T-lymphocytes, macrophages, mast cells and eosinophils. They were present throughout the evolutionary stages of the bronchiolitis ranging from early oedematous to the late fibrotic obliterative stage. Double immunohistochemical stains revealed negative proliferative cell nuclear antigen for most of the T-lymphocytes and macrophages but positive for fibroblasts. CONCLUSIONS: A more accurate histopathological designation of the SA-associated lung disease should be constrictive obliterative bronchitis/bronchiolitis, with the participation of T-lymphocytes, macrophages, mast cells, eosinophils and fibroblasts in its morphogenesis. The persistent accumulation of inflammatory cells was mediated predominantly by continued recruitment to the site of injury from the bloodstream, resulting eventually in the irreversible fibrosis of the bronchioles and the bronchi less than 3 mm in diameter. Obliterative arteriopathy is suspected of being only an indirect contributing factor.

Identification of upstream stimulatory factor as an activator of the human dipeptidyl peptidase IV gene in Caco-2 cells.

The 5' upstream region (-448/-443) of the human dipeptidyl peptidase IV gene promoter containing a consensus E-box (CACGTG) was shown to bind upstream stimulatory factor using nuclear extracts from mouse (3T3) fibroblasts and the human intestinal and hepatic epithelial cell lines Caco-2 and HepG2. Supershift analysis with specific antibodies to USF-1 and USF-2 indicates that USF-1 is the primary isoform binding to the E-box in nuclear extracts from these cells. Using cell culture, transient cotransfection of USF expression vectors with dipeptidyl peptidase IV promoter constructs revealed that both USF-1 and USF-2 caused an approximately tenfold increase in reporter gene expression in Caco-2 cells. Mutant forms of USF-1 and -2 lacking the DNA binding or transcriptional activation domains were unable to stimulate reporter gene expression. Mutation of the E-box prevented binding of USF, although stimulation of reporter gene expression by cotransfection with USF was reduced by only 50%. By using a series of deletion constructs in cotransfection experiments, a second possible site of USF interaction with the dipeptidyl peptidase IV promoter was localized to the -119/-88 region.

Do prostatic stents solve the problem of retention after transurethral microwave thermotherapy?

Temporary nonmetallic stents offer an alternative to an indwelling catheter for the management of voiding problems after heat-based therapies for benign prostatic hyperplasia. Patient comfort is improved, and they are able to void immediately after the procedure. Unlike a catheter, stents function on the principle of active drainage. Thus, a functioning detrusor muscle is imperative for stent success. Single-center clinical trials have reported encouraging results; however, predictable success criteria are yet to be established. Multicenter trial data are awaited.

Sauropus androgynus and papaverine do not induce bronchiolitis obliterans in Sprague-Dawley rats.

BACKGROUND: In August 1995, an outbreak of bronchiolitis obliterans was observed in Taiwan. This progressive respiratory distress disease was associated with consumption of the uncooked vegetable, Sauropus androgynus. The vegetable is reportedly high in papaverine, a chemical that affects vasodilatation. This study determined whether S androgynus and papaverine induce bronchiolitis obliterans in Sprague-Dawley (S/D) rats. METHODS: The feeding doses were derived from the mean amount (in mg/kg body weight) that humans had eaten. In part A of the experiment, 30 S/D rats were fed various concentrations of S androgynus juice for eight weeks. The rats were divided into six groups, including a normal control and study groups with one time (1X), 10 times (10X, leaf only and mixed leaf and stalk) and 30 times (30X, leaf only and mixed leaf and stalk) concentration. In part B, 33 S/D rats were fed different doses of papaverine for 4 weeks. The rats were also divided into six groups, including normal control, oral feeding subgroups (1X, 10X and 20X) and intraperitoneal injection subgroups (5X and 10X). The degree of inflammation was defined semiquantitatively in the bronchioles and pulmonary vessel adventitia as including grade 0 (no inflammation), grade 1 (minimal), grade 2 (mild), grade 3 (moderate) and grade 4 (severe). RESULTS: There was no evidence of bronchiolitis obliterans in either experiment. The histopathologic findings of the lungs revealed normal or only minimal inflammatory changes in the peribronchial and perivascular adventitia in each group of both studies. The mean degree of inflammatory changes in the study groups was no different from that of control group. CONCLUSIONS: We conclude that ingestion of high-dose S anggogynus and papaverine do not induce injuries to the airways, alveoli or pulmonary vessels in the animal model of S/D rats. The species barrier may be one of the possible reasons.

Role of hepatocyte nuclear factor 1alpha and 1beta in the transcriptional regulation of human dipeptidyl peptidase IV during differentiation of Caco-2 cells.

Caco-2 cells undergo differentiation to an enterocytic-like cell when maintained in a post-confluent state for 1-2 weeks. During this period Caco-2 cells begin to express high levels brush border membrane associated enzymes such as dipeptidyl peptidase IV. Using the dipeptidyl peptidase IV gene promoter in electrophoretic mobility shift assays, we have shown for the first time that levels of hepatocyte nuclear factor 1alpha increase three- to fourfold during Caco-2 cell differentiation. Transient cotransfection experiments with 3T3 cells using dipeptidyl peptidase IV promoter constructs and expression vectors containing hepatocyte nuclear factor 1alpha and beta show that the ratio of alpha and beta modulates reporter gene expression. These results suggest that the increase in levels of hepatocyte nuclear factor 1alpha that occur during intestinal cell differentiation, are important for expression of dipeptidyl peptidase IV and other intestinal proteins.

Evaluation of cytokeratin 19 fragment (CYFRA 21-1) as a tumor marker in malignant pleural effusion.

BACKGROUND: The aim was to investigate the diagnostic utility of CYFRA 21-1 (cytokeratin 19 fragment) as a tumor marker in pleural effusion and evaluate the value of combining CYFRA 21-1 and carcinoembryonic antigen (CEA) assays as a diagnostic aid in the malignant pleural effusion. METHODS: One hundred and twenty-six patients (72 malignant and 54 benign pleural effusion) were included in this retrospective study. The effusion levels of CYFRA 21-1 and CEA were measured using radioimmunometric assay. RESULTS: The median values of CYFRA 21-1 in benign and malignant pleural effusion are 15 and 70 ng/ml, respectively. Using a cut-off value of 50 ng/ml, defined at 94% specificity, the diagnostic sensitivity of CYFRA 21-1 for non-small cell lung carcinoma (n = 61), squamous cell carcinoma (n = 21), adenocarcinoma (n = 40) and small cell lung cancer (n = 11) was 64, 71, 60 and 18%, respectively. Regardless of cell types, the diagnostic sensitivity of CYFRA 21-1 and CEA in malignant pleural effusion (n = 72) was 57 and 60%, respectively (cut-off value of 10 ng/ml in CEA assay). Combining CEA with CYFRA 21-1, the diagnostic sensitivity may increase up to 72%, which was defined at 89% specificity. CONCLUSION: CYFRA 21-1 assay may be a useful tumor marker for discriminating benign from malignant pleural effusion, especially in those of non-small cell lung cancer. The combined use of CEA and CYFRA 21-1 assay in the malignant effusion may increase the diagnostic yield compared with CEA or CYFRA 21-1 alone.

Ethambutol-induced psychosis: a case report.

Clinically, ethambutol (EMB)-induced psychosis is rare. In our review of the literature, most cases of antituberculosis agent-associated psychoses were caused by isoniazid (INH). We report the case of a 51-year-old man with suspected tuberculosis (TB) pleurisy. An anti-TB trial with INH, rifampicin and EMB was given initially. Dizziness, disorientation, and auditory and visual hallucinations developed after seven days of therapy. Laboratory examinations, including routine biochemistry tests, serum titer of antinuclear antibodies, cerebrospinal fluid analysis and computerized tomography of the head showed no abnormal findings. Following discontinuation of anti-TB agents, the psychiatric symptoms subsided. When the patient was challenged with EMB, the same psychiatric symptoms recurred, but resolved again after discontinuation of EMB. It is important to be aware that EMB can induce psychosis when anti-TB medications are prescribed.

Intrathoracic extramedullary haematopoiesis complicated by massive haemothorax in alpha-thalassaemia.

Intrathoracic extramedullary haematopoiesis (EMH) is a rare entity that is usually asymptomatic. A 44 year old man with alpha-thalassaemia is described who developed dyspnoea and massive left sided haemothorax. The haemoglobin disorder was established by Hgb H staining and haemoglobin electrophoretic studies. The DNA analysis revealed it to be a case of double heterozygous terminal codon mutation with the genotype alphaalphaCS/alphaalphaT. Computed tomographic scanning and magnetic resonance imaging of the thorax showed multiple paravertebral masses which were found by thoracoscopic biopsy to be extramedullary haematopoiesis. Although no additional sclerosing pleurodesis or low dose radiation therapy was given, the lung expanded well and there has been no recurrence of haemothorax to date.

Regulation of the gene for human dipeptidyl peptidase IV by hepatocyte nuclear factor 1 alpha.

Hepatocyte nuclear factor 1 was identified as the transcription factor binding to a 20 bp (-150 to -131) region of the gene for human dipeptidyl peptidase IV, which has been shown to be important for the expression of dipeptidyl peptidase IV in the human intestinal and hepatic epithelial cell lines Caco-2 and HepG2. Functional analysis of the hepatocyte nuclear factor 1 site was performed with two minimal dipeptidyl peptidase IV promoter constructs (-250 to -41, and -150 to -41) with and without a 3 bp mutation in the hepatocyte nuclear factor 1 sequence, and used in transient transfection experiments with Caco-2 cells. The results show that the mutated constructs were able to drive transcription at only 5-10% of the activity of the non-mutated controls. Co-transfection of 3T3 cells with hepatocyte nuclear factor 1 (alpha or beta) and dipeptidyl peptidase IV promoter constructs (-250 to -41 or -150 to -41) resulted in a 2.5-6-fold increase in transcription over controls with hepatocyte nuclear factor 1 alpha but not with hepatocyte nuclear factor 1 beta. The results of this study show that hepatocyte nuclear factor 1 binds to the -150 to -131 region of the human dipeptidyl peptidase IV promoter and is necessary for transcriptional activation of the gene for dipeptidyl peptidase IV.

Churg-Strauss syndrome presenting with pulmonary capillaritis and diffuse alveolar hemorrhage.

Churg-Strauss syndrome (CSS) is a rare disorder characterized by the histopathological triad of systemic necrotizing vasculitis, extravascular granuloma, and eosinophilic infiltrate, occurring in individuals with asthma or a history of allergy. We report a case of CSS with rare presentation of diffuse pulmonary hemorrhage. A transbronchial lung biopsy showed necrotizing vasculitis, pulmonary capillaritis, and prominent eosinophilic infiltrate. At autopsy, necrotizing granuloma and diffuse alveolar hemorrhage were found in the lungs. Laboratory data showed hypereosinophilia, disseminated intravascular coagulopathy, and positive anti-proteinase 3 antineutrophil cytoplasmic antibody (ANCA). This case emphasize that CSS should be considered in the differential diagnosis of ANCA-positive vasculitis with diffuse alveolar hemorrhage.

Association of Sauropus androgynus and bronchiolitis obliterans syndrome: a hospital-based case-control study.

In late April 1995, an outbreak of a poorly defined respiratory illness related to the ingestion of leaves of Sauropus androgynus was observed in southern Taiwan. To further evaluate the association between S. androgynus and bronchiolitis obliterans syndrome, a hospital-based case-control study was conducted with one case group and three different control groups at Veterans General Hospital-Kaohsiung between April and September 1995. A total of 54 cases (50 females, 4 males), 54 age- and sex-matched neighborhood controls, 54 matched routine physical check-up controls, and 54 matched self-referred patron controls (who had ingested S. androgynus yet without obstructive physiology) were interviewed for clinical symptoms, history of S. androgynus consumption, and potential confounding factors. All 54 cases (100%) ingested S. androgynus compared with only five (9%) neighborhood controls (matched odds ratio (OR) incalculable, p < 0.001) and two (4%) physical check-up controls (matched OR incalculable, p < 0.001). In the univariate analysis of 54 cases and 54 self-referred patron controls, factors associated with an increased risk of bronchiolitis obliterans syndrome were methods of food preparation (uncooked juice vs. stir fried or boiled dishes, matched OR 10.3 (95% confidence interval (CI) 1.3-84.4)); preparer of the S. androgynus-containing food (vendor only vs. patient only or patient plus vendor, matched OR 2.8 (95% CI 1.1-7.1)); total S. androgynus consumption quantity (> 4,500 vs. 413-2,063 g, matched OR 10.0 (95% CI 1.9-53.0)); duration of consumption (> 45 vs. 6-24 days, matched OR 2.1 (95% CI 1.2-3.8)); and midterm interruption (< 2 vs. 2-5 days per week, matched OR 2.6 (95% CI 1.1-6.1)). Additionally, multiple conditional logistic regression analysis of cases and self-referred patron controls revealed that a larger total amount of S. androgynus consumption, preparation of S. androgynus food without cooking, and ingesting S. androgynus food prepared by a vendor were the significant risk factors associated with bronchiolitis obliterans syndrome.

Correlation of high-resolution CT and pulmonary function in bronchiolitis obliterans: a study based on 24 patients associated with consumption of Sauropus androgynus.

OBJECTIVE: An outbreak of Sauropus androgynus-associated bronchiolitis obliterans occurred in Taiwan in the summer of 1995. We undertook a study of the correlation between high-resolution CT findings and pulmonary function testing in patients from this outbreak. MATERIALS AND METHODS: We evaluated inspiratory-expiratory high-resolution CT scans of 24 patients with S. androgynus-associated bronchiolitis obliterans. The presence of bronchiectasis was assessed by two visual scores (a bronchial dilatation score and a bronchiectasis extent score). Extent of air-trapping was assessed visually and given a score. We also used computer software to assess the extent of air-trapping and generate scores of dynamic attenuation. Spirometry, plethysmography, and diffusion capacity of each patient were also obtained. RESULTS: All four scores had statistically significant correlation with forced expiratory volume in 1 sec (FEV1) (p < .05 for both bronchiectasis scores; p < .001 for both air-trapping scores). The two air-trapping scores had statistically significant correlation with forced vital capacity and diffusion capacity. We found the scores for dynamic attenuation had the greatest correlation with FEV1 (r = .85). We also found that mosaic attenuation was notable on expiratory CT scans alone in nine patients (type 1 air-trapping) and on both inspiratory and expiratory CT scans in 15 patients (type 2 air-trapping). In the latter group, FEV1 was significantly lower (p < .01). CONCLUSION: Findings from high-resolution CT of air-trapping were more important than findings of bronchiectasis when correlating pulmonary function with S. androgynus-associated bronchiolitis obliterans. Type 2 air-trapping suggested a more severe air-flow obstruction than did type 1. Scores for quantitative attenuation generated by computer software were helpful in assessing air-trapping and correlating it with pulmonary function. These findings may apply to patients with bronchiolitis obliterans from other causes.