OBJECTIVETo observe the correlation of gammaD-crystallin P23T mutant with lens ultrastructure of the hereditary coralliform cataract.

METHODSComplete ophthalmologic examinations were performed before lens extraction and lens samples were studied by transmission and scanning electric microscope respectively. Protein molecular modeling was performed using SWISS-MODEL(version 2.0).

RESULTSProtein structure modeling demonstrated that the mutant caused a decrease in molecular final total energy and changes in the surface structure of gammaD-crystallin. Ultrastructure study revealed crystals deposited in lens, extensive granules dispersed in uncommon oval structure and the disorganization of lens epithelial cells.

CONCLUSIONIt is possible that the gammaD-crystallin P23T mutant is associated with abnormal crystals in lens and disorganization of lens epithelial cells.

Cataract ; congenital ; genetics ; pathology ; Female ; Humans ; Lens, Crystalline ; ultrastructure ; Male ; Pedigree ; Phenotype ; Point Mutation ; gamma-Crystallins ; genetics

BACKGROUNDCongenital cataract is a sight-threatening disease that affects about 1 - 6 cases per 10000 live births and causes 10% - 30% of all blindness in children. About 25% of all cases are due to genetic defects. We identified autosomal dominant congenital coralliform cataracts-related genetic defect in a four-generation Chinese family.

METHODSComplete ophthalmological examinations were performed prior to lens extraction. Lens samples were then studied by electron microscopy. Genomic DNA from family members were examined using whole-genomic linkage analysis, with two-point logarithm of odds (LOD) scores calculated using the Linkage program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing. Finally, a three-dimensional protein model was predicted using Swiss-Model (version 2.0).

RESULTSEleven of the 23 examined individuals had congenital cataracts. Ultrastructure studies revealed crystal deposits in the lens, and granules extensively dispersed in transformed lens fiber cells. The maximum two-point LOD score, 3.5 at theta = 0.1, was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of gammaD-crystallin (CRYGD). Protein structure modeling demonstrated that the P23T mutation caused a subtle change on the surface of the gammaD protein.

CONCLUSIONSThe results suggest that the coralliform cataract phenotype is due to a mutated CRYGD gene, and that this sequence change is identical to one reported by Santhiya to be related to another distinct clinical condition, lamellar cataract. This study provides evidence that this same genetic defect may be associated with a different phenotype. This is the first report identifying the genetic defect associated with an autosomal dominant congenital coralliform cataract.

Cataract ; genetics ; pathology ; Female ; Genes, Dominant ; Genetic Linkage ; Humans ; Lens, Crystalline ; ultrastructure ; Male ; Microscopy, Electron ; Mutation, Missense ; gamma-Crystallins ; chemistry ; genetics

BACKGROUNDMiddle mediastinal masses comprise a wide variety of tumors but may also reflect lymphadenopathy, and thus remain an interesting diagnostic challenge. We performed positron emission tomography (PET) of mediastinal masses in order to evaluate the ability of PET to predict the malignancy of these tumors. We compared histologic findings, videomediastinoscopy, computed tomography (CT), and PET-CT in patients with mediastinal disease.

METHODSThirty-two patients were evaluated with CT, PET-CT and videomediastionoscopy, and all studies were performed within four weeks in each patient. (11)C-choline as a PET tracer was used to visualize masses. PET data were evaluated using the standardized uptake value (SUV) and were compared with pathologic data.

RESULTSThere were 13 men and 19 women aged from 21 to 74 (mean 45.2) years. Among the patients with mediastinal diseases, sarcoidosis was diagnosed in 12 patients, tuberculosis in 5 patients, lymphoma in 5 patients, and noncaseating granulomata without classical "sarcoid" finding in 3 patients. N2 or N3 nodal metastasis was revealed in 6 of 7 patients who had non-small cell lung cancer or suspected lung cancer, and one was negative (the pathological diagnosis was reactive hyperplasia). The accuracies for correctly diagnosing mediastinal masses for CT, PET-CT and videomediastinoscopy were 38% (12/32), 63% (20/32), and 91% (29/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 11.130, P < 0.001). The SUVs were similar among these diseases. On the other hand, if the diagnostic classification was benign vs malignancy, the accuracies for CT, PET-CT and videomediastinoscopy were 53% (17/32), 75% (24/32), 100% (32/32) respectively. The diagnostic accuracy of videomediastinoscopy was superior to that of PET-CT (chi(2) = 22.042, P < 0.001). The SUV of malignant lesions (6.9, 3.2 - 9.8; n = 11) appeared to be higher than that of benign lesions (4.9, 2.9 - 8.3; n = 21), however, this difference was not statistically significant (P = 0.054).

CONCLUSIONSTo diagnose lesions located in the middle mediastinum, videomediastinoscopy possesses the highest diagnostic accuracy, and therefore remains the gold standard. PET-CT is valuable for differential diagnosis of benign vs malignant lesions, CT alone or PET alone (SUV) may provide misdiagnosis in a substantial proportion of patients with mediastinal masses.

Adult ; Aged ; Carbon Radioisotopes ; Female ; Humans ; Male ; Mediastinal Diseases ; diagnosis ; Mediastinoscopy ; methods ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed ; Video Recording

Adult ; CD8-Positive T-Lymphocytes ; immunology ; Case-Control Studies ; Female ; Hepatitis B, Chronic ; immunology ; metabolism ; pathology ; Humans ; Liver ; immunology ; pathology ; Male ; Middle Aged ; T-Cell Antigen Receptor Specificity ; Young Adult

Endoplasmic reticulum (ER) stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. The purpose of the present study was to investigate the effects of caveolin-1 (Cav-1) on ER stress-induced apoptosis in cultured macrophages and the underlying mechanisms. RAW264.7 cells were incubated with thapsigargin (TG) to establish ER stress model. And Cav-1 expression was detected by Western blot. After being pretreated with filipin(III), a caveolae inhibitor, RAW264.7 cells were assayed with flow cytometry and confocal laser scanning microscopy to detect cell apoptosis. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation and C/EBP homologous protein (CHOP) expression were detected with Western blot. The results showed that Cav-1 expression was markedly increased at early stage of TG treatment (P < 0.05) and then decreased with prolonged or high dose TG treatments. The increasing of Cav-1 expression induced by TG in RAW264.7 cells was abolished under inhibition of caveolae by filipin(III) (P < 0.05). The effect of TG on apoptosis of RAW264.7 cells was further augmented after pretreatment with filipin(III) (P < 0.05). Western blotting showed that MAPK phosphorylation induced by TG was inhibited by filipin(III) in RAW264.7 cells (P < 0.05), whereas CHOP remained unchanged (P > 0.05). These results suggest that Cav-1 may play a critical role in suppressing ER stress-induced macrophages apoptosis in vitro, and one of the mechanisms may be correlated with the activation of p38 MAPK prosurvival pathway.
Animals ; Apoptosis ; drug effects ; Caveolin 1 ; genetics ; metabolism ; Cell Line ; Endoplasmic Reticulum Stress ; physiology ; Filipin ; pharmacology ; MAP Kinase Signaling System ; Macrophages ; cytology ; drug effects ; Mice ; Thapsigargin ; pharmacology ; Transcription Factor CHOP ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo identify the genetic defect for the autosomal dominant coralliform cataract affecting a four-generation Chinese family.

METHODSGenomic DNA from the family members was typed for whole genomic linkage analysis. Two-point LOD scores were calculated using the LINKAGE program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing.

RESULTSThirteen of the 38 individuals had congenital cataracts. The maximum two point LOD score, 3.5 at theta=0.1 was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin gene cluster identified a C --> A mutation in exon 2 of gamma-D crystallin gene (CRYGD) associated with cataracts in this family. This mutation resulted in a substitution of threonine for proline at amino acid 23 (P23T) of the protein.

CONCLUSIONThe results suggest that the coralliform cataract phenotype is due to a mutated gamma-D gene, and the sequence change is identical with that recently reported to be related with lamellar cataract, a distinct clinical entity, thus providing evidence that the same genetic defect may be associated with different opacity location. The pathogenesis needs further investigation.

Base Sequence ; Cataract ; diagnosis ; genetics ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Family Health ; Female ; Genes, Dominant ; genetics ; Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Lod Score ; Male ; Mutation ; Pedigree ; Phenotype ; Protein Isoforms ; genetics ; gamma-Crystallins ; genetics

OBJECTIVETo assess and compare the effectiveness and safety of methylphenidate immediate-release tablets (IR-MPH), methylphenidate controlled release tablets (OROS-MPH) and atomoxetine (AHC) for attention deficit hyperactivity disorder (ADHD) in Chinese children.

METHODSRandomized or clinical controlled trials on the effectiveness and safety of IR-MPH, OROS-MPH and AHC for ADHD were searched in electronic databases of CNKI, VIP, CBMDISC online, PubMed, Embase and MEDLINE. Two reviewers independently extracted the data and assessed the quality of the included literatures.

RESULTSEight trials were finally included. IR-MPH, OROS-MPH and AHC were effective for ADHD. OROS-MPH was superior to IR-MPH in the improvement of peer relationship, CGI-I score, mother satisfaction and psychosomatic problems. There were no significant differences in the effectiveness between the AHC and IR-MPH groups. The adverse events related to the therapy with IR-MPH, OROS-MPH or AHC were mild and the incidence rates of adverse events were not significantly different among the three groups.

CONCLUSIONSThe effectiveness of OROS-MPH for the treatment of ADHD is probably superior to IR-MPH, and the effectiveness between AHC and IR-MPH is similar. The three drugs demonstrate the safety and well tolerance.

Atomoxetine Hydrochloride ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Delayed-Action Preparations ; Humans ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Propylamines ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Tablets

Objective To investigate the number and distribution of un-repaired cleft lip/palate patients in Gansu province. Methods A census was conducted by staff members of the health system and Population and Family Planning Committee (PFPC) in Gansu province. Standardized -Questionnaires were administered to collect demographic, domestic and diagnosis-related information. Results In 2008, the total number of un-repaired cleft lip/palate patients was 4675,with a detection rate of 1.84/10 000 in Gansu province. Rates of detection were higher in males (2.11/10 000), young age group(4.86/10 000), rural areas(2.23/10 000),poor counties(2.19/10 000)than in females(1.43/10 000), medium (0,97/10 000)/old age group(0.68/10 000), township areas (0.62/10 000), or richer counties (1.35/10 000). Among all the cities and prefectures of Gansu,Baiyin city (2.7/10 000) had the highest while Jinchang city (0.7/10 000) had the lowest prevalence rates. Conclusion Un-repaired cleft lip/palate had been a disease burden to Gansu province,especially in the rural area and poorer counties.

Antitubercular Agents ; adverse effects ; Chemical and Drug Induced Liver Injury ; prevention & control ; Chemoprevention ; China ; Clinical Trials as Topic ; Humans ; Protective Agents ; therapeutic use ; Tuberculosis ; drug therapy

OBJECTIVETo evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure.

METHODSIn this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared.

RESULTSA total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting.

CONCLUSIONGTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.

Adult ; Double-Blind Method ; Female ; Fissure in Ano ; drug therapy ; Humans ; Male ; Middle Aged ; Nitroglycerin ; therapeutic use ; Treatment Outcome