Insulin-like Growth Factor-Ⅰ Gene Cloning and Protein Expression in Bovine Trabecular Meshwork Tissue and Cells

Primary open- angle glaucoma(POAG) is aleading cause of blindness,which involves opticneuropathy accompanied by characteristic visualfield defects and is often associated with elevatedintraocular pressure due to disturbance of aqueoushumor outflow through the trabecular meshwork(TM) [1] .The pathophysiology of the TM inPOAG has been characterized by an increase in ex-tracellular matrix components and a decrease in thenumber of TM cells[2 ] .Polypeptide growth factorsare critical modulator…     

Effect of Transforming Growth Factor-β_2 on Phagocytosis in Cultured Bovine Trabecular Meshwork Cells

A gradual loss of cells occurs within the humantrabecular meshwork (TM) during normal aging andappears to be increased in patients with primary openangle glaucoma (POAG) [1] .The exactmechanism bywhich cells are lost in either condition is not known,however phagocytosis has been suggested[2 ] .It hasbeen found that,when compared with the non- POAGpatients,the level of transforming growth factor- β2(TGF- β2 ) which may be involved in the pathogenesisof POAG increased in the aqueous humo…     

INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-I (PAI-I) inwomen with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Results. Circulating levels of TM, PAI-I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. Conclusion. TM and PAI-I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.     

Analysis of MYOC gene mutation in a Chinese glaucoma family with primary open-angle glaucoma and primary congenital glaucoma

Background Glaucoma is one of the leading causes of blindness in the world. Primary open-angle glaucoma （POAG） and primary congenital glaucoma （PCG） are subtypes of glaucoma. Myocillin is the first gene identified to be involved in POAG. Recently, myocillin mutation has been found in PCG. In this context, we reported a special glaucoma pedigree, which was composed of both PCG and POAG patients, and analyzed the mutation of myocillin in this pedigree. Methods The family was composed of the parents, a son and a daughter. All members of the family underwent the complete ophthalmologic examinations. All coding exons 1-3 and flanking introns of myocilin gene were screened for sequence alterations by polymerase chain reaction and direct DNA sequencing. Results The son was the proband, who was diagnosed as PCG in both eyes. The father was diagnosed as POAG in the right eye, the left eye was still normal. Both the sister and the mother of the proband had normal intraocular pressure without glaucomatous optic disc changes. The mutations in intron 2 of myocilin gene were detected in the family. While the proband and the father were homozygous, the mother and the sister were heterozygous for the mutation. Conclusions Homozygous mutation in intron 2 of myocilin gene is involved in both POAG and PCG. It is suggested that the pathogenesis might be overlapping in POAG and PCG.     

Neural histamine in the tuberomammillary nucleus regulates the onset of neurogenic pulmonary edema in rabbits

Objective:To explore the effect of neural histamine in the tuberomammillary nucleus(TM) on neurogenic pulmonary edema (NPE) onset in rabbits and the function of the rostral ventrolateral medulla(RVLM) in the neural histamine modulation of NPE. Methods: NPE was produced by the intracisternal injections of fibrinogen and thrombin. The contents of histamine in the TM and RVLM in rabbits were measured with high performance liquid chromatography(HPLC). Rabbits were placed on a stereotaxic frame and microinjectio...     

Neuroretinal rim area in early glaucoma.

Neuroretinal rim area (NRA) is the only clinical measurement that reflects the real amount of nerve fibers in optic disc. We measured the photographs of the optic disc in 132 eyes of 132 subjects in 6 groups: normal subjects with small cups, normal subjects with large cups, suspected glaucoma with small cups and those with large cups, primary open angle glaucoma (POAG), low tension glaucoma (LTG). The mean NRAs of POAG, LTG and suspected glaucoma with large cups were less than those of normal subjects with large cups. In normal subjects, a high correlation between cup area and disc area was found, while NRA correlated weakly with disc area. Both semiquantitative scores of diffuse and localized retinal nerve fiber layer defects were correlated significantly with NRA. We suggest that measurement of NRA and examination of retinal nerve fiber layer defect could improve the detection of acquired changes of optic disc in early glaucoma.

     

Inhibitory Effect of Tissue Transglutaminase （tTG） Antisense Oligodeoxynucleotides on tTG Expression in Cultured Bovine Trabecular Meshwork Cells

To study the effect of tTG fully phosphorothioated antisense oligodeoxynucleotides （tTG-ASDON） on tTG expression in cultured bovine trabecular meshwork cells （BTMCs） in vitro and explore a new treatment alternative for primary open angle glaucoma （POAG）, the ASDON1 and ASDON2 complementary to the protein codogram region of tTG were designed, synthesized and phosphorothioated according to the secondary structure of tTG. The ASDON1 and ASDON2 were embedded in Lipofectamine and transfected into BTMCs. The untreated group served as negative controls. The expression of tTG in the mRNA and protein level were measured by semi-quantitative RT-PCR and immunohistochemical technique-Supervision method respectively. Our results showed that both the mRNA and the protein of tTG with tTG-ASDON1 and tTCr-ASDON2 were significantly decreased as compared with that of the controls （P〈0.05）. On the other hand, no significant difference was found between the ASDON1 group and the ASDON2 group. It is concluded that the expression of tTG mRNA and protein in cultured BTMC are down-regulated by tTG- ASDON. As a result, tTG-ASDON may be used for the treatment of POAG through the inhibitory effect on the expression of tTG.     

Benign symmetric lipomatosis of the knees

Benign symmetric lipomatosis(BSL)is a rare disease characterized by the presence of multiple,symmetric and nonencapsulated fat masses in the face,neck and other areas.It is commonly seen in middle-aged Caucasian Mediterranean males,while its etiology is still not clear.The majority of the patients with BSL have a history of alcohol abuse and hepatopathy.BSL of the limbs is very rare.This article reports a unique case of a 60-year-old Chinese woman with involvement of the knees confirmed by the results of magnetic resonance imaging(MRI)and histopathology,which was not described previously in published literatures.     

Cardiac troponin T mutations in Chinese patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by unexplained ventricular hypertrophy and myofibrillar disarray, with a prevalence of about 0.2% in general population. HCM is associated with gene abnormalities. Nearly 200 mutations have been described in ten genes in patients with HCM.1 Cardiac troponin T (cTnT) is an essential component of the troponin complex and plays a central role in the calcium regulation of contractions in cardiac myocytes     

Lutembacher syndrome: an ideal combination for percutaneous treatment

To the Editor : I read with interest the case report by Shen et al1 of transcatheter treatment of Lutembacher syndrome. Lutembacher syndrome refers to a congenital atrial septal defect (ASD) complicated by acquired mitral stenosis (MS).2 The incidence of MS in patients with ASD is 4%, the incidence of ASD in patients with MS is 0.6%-0.7%.2 Lutembacher syndrome in the past has been overdiagnosed or misdiagnosed because of the presence of a mid-diastolic murmur in patients with ASD, until it was realized that the mid-diastolic murmur was due to excessive flow through the tricuspid valve from the left-to-right interatrial shunt.     

The relationship between gap junctional remodeling and human atrial fibrillation

Atrial fibrillation (AF) is currently the most common cardiac tachyarrhythmia in clinical practice. AF has a tendency to become more persistent over time. Progression of an underlying disease is one explanation. Another possible explanation is electrical, structural, and gap junctional remodeling of the atrium by repetitive induction of AF.1 The expression level and distribution of it have close relation with the conduction velocity of electrical activation in the atrium. The aim of the present study was to investigate the alternations of the expression and distribution of (connexin 40, Cx 40) and (connexin 43, Cx 43) in the right atrial appendages of the patients with AF by laser confocal scanning microscopy and Western blot technique.     

The relationship between gap junctional remodeling and human atrial fibrillation

Atrial fibrillation (AF) is currently the most common cardiac tachyarrhythmia in clinical practice. AF has a tendency to become more persistent over time. Progression of an underlying disease is one explanation. Another possible explanation is electrical, structural, and gap junctional remodeling of the atrium by repetitive induction of AF. The expression level and distribution of it have close relation with the conduction velocity of electrical activation in the atrium. The aim of the present study was to investigate the alternations of the expression and distribution of ( connexin 40, Cx 40) and ( connexin 43, Cx 43) in the fight atrial appendages of the patients with AF by laser confocal scanning microscopy and Western blot technique.     

Strategies for Revitalization of Traditional Medicine

Traditional medicine (TM) plays an inevitable role in drug discovery and development. Most of the therapeutically useful molecules used in the present day are inspired from TM. Herbal drugs are the oldest forms of medicines used for the treatment of various ailments and the TM of every country has a long history of their usage. To develop more data on their quality, safety, and efficacy, so also to improve the consumer’s need of modern days several thrust areas of research are to be focused on the development of TM. Based on the above concept, a paradigm shift is required for the revitalization of TM. These facts along with the modern scientific approaches, molecular tools, and strategies make it necessary for TM to be revitalized. Confluencing several strategies with the technological and scientific developments including pharmacogenomics, nutrigenomics, system biology, and related approaches, the scientific potential of TM can be explored further with international coordination and collaborations.     

Endogenous erythroid colony assay in patients with polycythemia vera and its clinical significance

Background Polycythemia vera (PV) is a malignant disorder of hemaopoietic stem cells which is characterized by clonal hyperproliferation and a low rate of apoptosis. This study was to assess endogenous erythroid colony (EEC) formation in the bone marrow of PV patients and determine its clinical significance.Methods The bone marrow mononuclear cells of 26 patients with PV, 2 patients with secondary erythrocytosis (SE), and 19 normal controls were cultured by Marsh‘ s method for EEC evaluation,and the clinical significance was evaluated.Results EECs appeared in 25 patients with PV but not in 2 patients with SE and 19 normal controls.The number of EECs and the EEC ratio [ EEC/erythropoietin ( EPO)-dependent colony forming uniterythroid (CFU-E)] in PV patients positively correlated with hemoglobin (Hb) levels. Their EEC number did not correlate with white blood cell (WBC) counts, platelet (PLT) counts, or leukocyte alkaline phosphatase (LAP) scores. Their EEC did not correlate with serum EPO levels. Fifteen patients with PV were treated with hydroxyurea ( Hu ) and/or interferon-alpha (IFN-α). Their EEC ratio before treatment positively correlated with the treatment time required for complete remission (CR) and negatively correlated with the time before relapse. The EEC numbers of 7 PV patients treated with Hu/IFN-α decreased after the blood cell counts dropped to normal levels. There was a positive correlation between the EEC ratio and the incidence of attacks of vascular thrombosis in PV patients. The numbers of apoptosised bone marrow mononuclear cells in PV patients were lower than those in normal controls. The EEC numbers of PV patients negatively correlated with the rate of apoptosis of bone marrow mononuclear cells.Conclusions EEC formation is characteristic in PV patients. EEC number in PV patients positively correlates with Hb levels, the time required for CR, and the incidence of attacks of vascular thrombosis. EEC number negatively correlates with the time before relapse. Bone marrow suppressive treatment might decrease EEC number. Thus, EEC number is a sensitive and specific parameter reflecting the abnormal hematopoietic clone burden induced by polycythemia vera. EEC number is an important diagnostic parameter for PV patients.     

Management of gastric cancer in patients with sinistral portal hypertension

Sinistral portal hypertension (SPH) is usually caused by pancreatic pathology and is characterized by splenic vein thrombosis with or without portal vein thrombosis.1 The increased pressure caused by splenic vein occlusion is transmitted via the short gastric and gastroepiploic veins to the portal system.The reversal of blood flow in the left gastric vein results in gastric varices.In patients with SPH,especially those with occlusion of both the splenic and portal veins,the main or even the only pathway of splenic venous return to the portal vein is via the gastric varices,and these patients require special management during gastric surgery.     

Mechanism of peripheral blood mononuclear cell invasion by HBV on artificial immunization in newborns

Objective To study the effect and mechanism of the peripheral blood mononuclear cell (PBMC) invasion by HBV on artificial immunization in newborns.Methods Fifty- two newborns of HBsAg positive mothers were immunized with HBIG (hepatitis B immunoglobulin) and HBVac (hepatitis B vaccine) and were followed up for 7 months. The newborns’ HBV- DNA in serum and in the PBMCs was detected with nested- PCR; anti- HBs was tested with solid phase radioimmunoassay (SP- RIA). PBMCs isolated from newborn peripheral blood were incubated in the presence of PHA or purified HBsAg. Interleukin- 2 (IL- 2) level in culture supernatants of activated cells was detected by ELISA.Results The failure rate of immunization was higher in infants with positive HBV- DNA in PBMCs than those with negative HBV- DNA (P<0.05); IL- 2 level in PBMC culture supernatants was lower in former than in the latter and in normal controls (P<0.05). The level of IL- 2 in the immunization failure newborns was lower than that in the successfully immunized newborns and in normal controls (P<0.05).Conclusions Intrauterine invasion of PBMCs by HBV is one of the important reasons for immunization failure in newborns. IL- 2 production is closely related to the invasion of PBMCs by HBV, which may contribute to the failure of artificial immunization in newborns.     

Rac1 regulates the release of Weibel-Palade Bodies in human aortic endothelial cells

Background The release of Weibel-Palade Bodies (WPB) is a form of endothelial cell activation. But the signal transduction pathway leading to WPB release is not yet defined. We hypothesized that small G-protein racl and reactive oxygen species (ROS) mediate the ligand induced release of WeibeI-Palade Bodies. Methods We tested this hypothesis by using wild-type and mutant adenoviral racl expression vectors, and by manipulating the production and destruction of superoxide and hydrogen peroxide in human aortic endothelial cells (HAEC). Results Thrombin (1.0 Unit, 30min) induced the increase of WPB release by 3. 7-fold in HAEC, and that H2O2 (0. 1mmol/L, 30 min) induced by 4. 5-fold. These results correlated with thrombin-stimulated activation of rac-GTP binding activity by 3. 5-fold, and increase of ROS production by 3. 4-fold. The dominant negative adenoviral rac-N17 gene transfer dramatically inhibited the release of WPB by 64.2% (control) and 77.3% (thrombin-stimulation), and decreased ROS production by 65.5% (control) and 83.6% (thrombin-stimulation) compared with non-infected cells, respectively. Anti-oxidants, catalase and N-acetyl-cysteine significantly decreased the release of WPB by 34% and 79% in control cells, and further decreased by 63.6% and 46.7% in rac-N17 transferred cells compared with non-infected cells. We also confirmed that racl was located upstream of ROS in the WPB release pathway. Conclusions Small G-protein racl medicates ligand-induced release of WeibeI-Palade Bodies in human aortic endothelial cells, and the signal pathway of WPB release is a racl-dependent ROS regulating mechanism.     

Metformin for adolescents with polycystic ovary syndrome

Polycystic ovary syndrome(PCOS) is a common endocrine disorder in women of reproductive age characterized by chronic anovulation, hyperhandrogenism, and is increasingly recognized as a disease developed in adolescent period. The management of adolescents with PCOS is a difficult challenge. The objective of the review was to provide an overview on the effects of metformin for adolescents with PCOS.     

Recent advances and findings of angiotensin type 2 receptor:a review

Angiotensinogen is a member of the serpin family. It is produced constitutively and released into the circulation mainly by the liver. Angiotensinogen forms angiotensin Ⅰ by action of the circulated renin released from the kidney. Angiotensin Ⅱ (Ang Ⅱ), an octapeptide hormone with sequence Asp-Arg-Val-Tyr-Ile-His-Pro-Phe,is converted from angiotensin Ⅰ through removal of two terminal residues by the angiotensin-converting enzyme (ACE) mostly catalyzed in the lung.1 This peptide binds to two subtype receptors, angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R),members of the superfamily of heptahelical G protein coupled receptors, with different affinities.2 It is well known that AT1R and AT2R crosstalk and lead to counterregulatory functions in many systems, especially the cardiovascular system.3 Accumulating data established the roles of AT1R in the classic actions of Ang Ⅱ including vasoconstriction and cardiovascular hypertrophy, whereas AT2R is suggested to exert direct functions in vasodilation and antigrowth effects.4 Recent publications provide new insights into the roles of AT2R with increasing responsibilities. Recent progresses in AT2R research are reviewed in this article.