Clinical and genetic diagnosis in a hereditary hemorrhagic telangiectasia family / 中南大学学报(医学版)

Objective:To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family,and to explore the application of gene mutation testing in HHT diagnosis.Methods:Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria.Sequence analysis of endoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performed with PCR and Sanger sequencing technology.After the possible pathogenic mutation was identified in the proband,the specific mutation was detected in the suspected individuals and part of other family members.Then the genetic diagnoses were concluded.Results:There were 5 family members in 4 generations manifested with epistaxis.According to the clinical diagnosis criteria,the proband with epistaxis,mucocutaneous telangiectases,visceral arteriovenous malformation and family history was diagnosed as HHT;while 2 survival family members with epistaxis and family history were suspected individuals.A substitution mutation in the 5'-untranslated region(5'-UTR) of ENG c.1-127 C＞T was detected in the proband and the 2 suspected individuals,which did not exist in other family members.Based on the clinical and genetic findings,the 2 clinically suspected individuals were diagnosed as HHT.Conclusion:There is great variability of the clinical manifestations among HHT patients.ENG c.1127 C＞T mutation is the possible pathogenic variant of the HHT family.A combination of clinical and genetic diagnosis could improve the diagnosis and treatment of HHT.

Clinical analysis on extramedullary plasmacytoma in the upper airway / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the clinical manifestation, treatment and prognosis of extramedullary plasmacytoma(EMP) in the upper airway, and to improve the diagnosis and outcome of EMP treatment.@*METHOD@#Clinical data of 26 EMP cases were reviewed retrospectively, and then compared with multiple myeloma(MM) patients presenting with lesions in upper airway.@*RESULT@#Of 26 cases, 9 cases with the tumors occurred in nasal cavities, 7 in nasal sinuses, 6 in pharyngeal, 4 in throat, mainly manifesting with local masses and relevant symptoms. The manifestations of clinical, endoscopy findings and pathologic results in EMP patients were not distinguishable from the lesions of MM patients, while MM patients often accompanied by other findings, such as anemia and bone damage. Involvement of neck lymph nodes was more common in MM patients than in EMP patients. Ten patients were treated with surgery, and 16 patients with surgery and radiotherapy. Of the seven EMP patients with involvement of neck lymph nodes, four patients received additional chemotherapy besides surgery and radiotherapy, and no local relapse and MM happened in them, while of the three patients only received surgery and radiotherapy, one local relapse were found and one progressed to MM.@*CONCLUSION@#The diagnosis of EMPs mainly depends on pathological results. The judgment of pathologists and application of molecular biology technology are vital for the diagnosis of EMP in upper airway, and MM must be excluded very carefully in the diagnosis of EMP. Surgery combined with radiotherapy is the main treatment for EMP in the upper airway, and the prognosis is good but the follow-up should be taken. Besides surgery and radiotherapy, chemotherapy is beneficial for the EMP patients accompanied with lesions in neck lymph nodes.

Expression of proteinase TMPRSS3 in mouse cochlea / 中南大学学报(医学版)

OBJECTIVE@#To observe the expression of proteinase transmembrane protease, serine 3 (TMPRSS3) in mouse cochlea, and to investigate the significance of TMPRSS3 in the inner ear.@*METHODS@#The protein expression of TMPRSS3 in C57/BL mouse cochlea was identified and detected by immunohistochemistry and immunofluorescence. Different cochlear tissues, such as spiral ganglion neurons, corti organ, stria vascularis and so on, were separated to detect the gene expression of TMPRSS3 by real-time fluorescence quantitative polymerase chain reaction (qPCR). The cochlear tissues with different ages were collected and the expression of TMPRSS3 mRNA was detected by qPCR.@*RESULTS@#TMPRSS3 was mainly expressed in the spiral ganglion neurons, and there was TMPRSS3 mRNA in the cochlea in groups with different age. The expression level of TMPRSS3 mRNA was much weaker.@*CONCLUSION@#The distribution of TMPRSS3 was observed in many regions of the mouse cochlea, but mainly in the spiral ganglion neurons. This indicates that TMPRSS3 may be involved in the physiological functional regulation of the spiral ganglion neurons.

Expression of TMPRSS3 in the rat cochlea following kanamycin ototoxicity / 中南大学学报(医学版)

OBJECTIVE@#To establish the kanamycin-induced deafness model in SD rats, and to investigate the expression and significance of transmembrane protease, serine 3 (TMPRSS3) in the cochlea following kanamycin ototoxicity.@*METHODS@#A total of 40 male SD rats were randomly divided into 4 groups. The experimental rats received intramuscular kanamycin sulfate for 3, 7, and 14 consecutive days, and the control group were treated with normal saline for 14 days. Auditory brainstem responses (ABR) were obtained before and after the kanamycin administration. The expression of TMPRSS3 in the cochlea was identified and detected by immunohistochemistry and Western blot.@*RESULTS@#Kanamycin-induced deafness model in the SD rats was successfully established. ABR thresholds were increased and the expression of TMPRSS3 in the cochlea was reduced after the kanamycin injection (P<0.01).@*CONCLUSION@#TMPRSS3 may play an important role in normal cochlea function and involve in the process of aminoglycoside antibiotics induced deafness.

Study on the surgery treatments in patients with maxillary osteofibrous hyperplasia of bone / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the clinical features, diagnosis and the surgery therapy of maxillary fibrous hyperplasia of bone.@*METHOD@#The clinical data of 37 cases with maxillary fibrous hyperplasia of bone from 1987-2006 years were retrospectively analyzed. 19 cases of male and 18 cases of female, their average age is 22.5 years (17-35 years). Twenty-one cases were operated by Caldwell-lud or lateral rhinotomy operation. After 1997, 16 cases were operated by Caldwell-lud operation with endoscopy so as to strip hyperplasia bone.@*RESULT@#Thirty-six cases were cured within 2-4 years follow-up, 1 case was reoperated by Caldwell-lud operation with endoscopy after recurrence. The patients who received operation by Caldwell-lud operation with endoscopy had less symptoms in the inflation deformity of maxillofacial region and dysfunction of neighbouring structures than those who received traditional operation.@*CONCLUSION@#The diagnosis can be made by history, signs and radiography. Caldwell-lud operation with nasal endoscopy is more effective treatment, and advocated in clinical practice.

Clinical features and treatment of nasal mucosa-associated lymphoid tissue lymphoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the clinical features and treatment of nasal mucosa-associated lymphoid tissue lymphoma (MALTL).@*METHOD@#The data of 11 patients with nasal MALTL were analyzed retrospectively during 9 years, including their clinical features and effectiveness of treatment. Nine cases were male and 2 female, their age arranged from 18 to 49 years with an average age of 39 years. All cases underwent endoscopic sinus surgery, and were diagnosed by HE staining and immunohistochemistry. After operation, 7 cases were cured with immunotherapy and antibiotic therapy. Other 4 patients were treated by chemotherapy, radiotherapy, immunotherapy and antibiotic therapy.@*RESULT@#During follow up 6-36 months, 4 patients died and other 7 patients achieved complete remission.@*CONCLUSION@#Clinical manifestations of nasal MALTL are not typical,which is apt to be misdiagnosed and mistreated. The suspected lesion tissues under endoscopy should be completely resected and submitted to pathology investigation. Nasal MALTL is a subtype of non-Hodgkin lymphoma which is characterized by occult onset, long course, slow progression and low cure rates in the advanced stage.

Differentially expressed proteins of the fibroblast cell-secreted protein in nasopharyngeal carcinoma / 中华检验医学杂志

Objectives To establish the two-dimensional electrophoresis(2-DE)profile of cell. Secreted proteins.Difierential expression profiling of fibroblast cell secreted proteins between nasopharyngeal carcinoma and normal nasopharyngeal tissue was analyzed.Methods Five tissue specimens each from patients with nasopharyngeal carcinoma and nasal polyp were collected individually.Fibroblast eells from above-mentioned tissue were cultured in serum-free medium,and cell-secreted proteins from the cultured medium were harvested by uhrafihration concentration and desalination.Samples were analyzed by 2-DE,and the differentially expressed proteins were analyzed and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry.Galectin-1 wa8 analyzed by EUSA test.Results 2-DE diagram of fibroblast cell-secreted proteins Was constructed.1 8 protein spots displayed quantitative changes in expression,and 11 protein spots among them were identified by mass speetrometrv.3 proteins including cystatin C,complement subcomponent C1S precursor,heterogeneous nuclear ribonueleoprotein A1 were down-regulated in the cultured medium of nasopharyngeal carcinoma associated fibroblast cells(CAFs). Nevertheless,the rest cell-secreted proteins including galectin-1,14-3-3 protein sigma,eathepsin L and etc,were up-regulated.Meanwhile,the expression of galectin-1 in the cultured medium was also analyzed and Its results were compared between CAFs and the normal fibroblast cells by ELISA.There Was statistical significance difference between them,and galectin-1 was up-regulated in the cIlltured medium of CAFs.Conclusions The changes of fibroblast cell-secreted proteins during nasopharyngeal carcinogenesi8 are analyzed by 2-DE analysis.The variation of pattern of secreted proteins is involved in signal transduction,protein synthesis,degradation and other pathways.CAFs may regulate tumor microenvironment by the abeve-mentioned pathways,and influence nasopharyngeal carcinogenesis,progress,invasion and metastasis.This study provided experimental basis for the eell secreted proteomics studv in future.

A Member of Ⅱ Transmembrane Serine,TMPRSS3 and Hereditary Deafness / 生物化学与生物物理进展

TMPRSS3 (transmembrane protease, serine 3) is a member of Ⅱ transmembrane serine proteases (TTSPs), and like the other members of this family, it contains typical domains including a serine protease domain, a transmembrane domain, a LDL receptor-like domain (LDLRA), and a scavenger receptor cysteine-rich domain (SRCR). Four alternative protein isoforms have been described, and isoform A is thought to be primary isoform which is expressed in many tissues, especially in the cochlea. TMPRSS3 protein is primarily localized in the endoplasmic reticulum membranes where it may be anchored by its transmembrane domain. TMPRSS3 is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). Therefore TMPRSS3 is thought to be involved in the development and maintenance of the inner ear, and isoform D may be proposed as a novel diagnostic marker in ovarian carcinoma. TMPRSS3 protein is the first protease which mutation could lead to deafness. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage. However, it is not clear about TMPRSS3 substrates and its function. The epithelial amiloride-sensitive sodium channel (ENaC) which is regulated by membrane-bound channel activating serine proteases (CAPs), a member of TTSPs, may be a potential substrate of TMPRSS3, but this hypothesis is still to be verified in vivo. With the development of protease research and the application of protease proteomics, substrate degradomes of a protease may therefore represent an important tool for the research of TMPRSS3 function and its molecular mechanism.

Construction of Human Brain-Derived Neurotrophic Factor Genetical Modified Marrow Stromal Cells and Its Influence on the Cultured Spiral Ganglion Cells of Mice / 听力学及言语疾病杂志

Objective To establish human brain-derived neurotrophic factor (BDNF) genetical modified marrow stromal cells and to evaluate the influence on the viability of the cultured spiral ganglion cells from Kunming mice.Methods Eukaryotic expression plasmid——pcDNA3.1(-)-BDNF was constructed according to the molecular clone approach. Marrow stromal cells(MSC) were separated and cultured. BDNF genetical modified marrow stromal cells were established and verified by biochemical analysis.The bio-effect to spiral ganglion cells, especially with the oxidative damage under the different concentration of H_2O_2 was observed.Results PcDNA3.1(-)-BDNF and BDNF genetical engineering cells were successfully established. The supernatant from BDNF-MSCs remarkably improved the survival rate of the spiral ganglion cells.Conclusion BDNF genetical modified marrow stromal cells are successfully established, and the genetical engineering cell plays an important role in the protection the spiral ganglion cells from the oxidative damage. This study provide a strong basis for genetical engineering cells transplantation into the inner ear.

Protective Role of BDNF and NGF Against Cisplatin-Induced Ototoxicity / 听力学及言语疾病杂志

Objective To study the expression of brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) in the guinea pig cochlea of cisplatin-induced ototoxicity, and to understand its protective role for the inner ear.Methods The animals were divided into normal group and experimental group with cisplatin. Sodium chloride was used for the control. All animals were sacrificed on the day 3, 5 and 7, and the cochlea were used for BDNF and NGF staining.Results The weak expression of BDNF and the moderate expression of NGF were observed in the cochlea in the normal group. The strongest expression of BDNF and NGF was observed in the animals with cisplatin.Conclusion The existence of NGF in the normal cochlea indicates that NGF plays an important role to maintain auditory physiology.BDNF and NGF may be involved in self-protection mechanism for the cochlea and auditory nerves from cisplatin-induced ototoxicity.