Inhibin B, activin A, and follistatin and the pathogenesis of polycystic ovary syndrome.
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Biomedical subjects
Publications and source records attributed to Z J Shen.
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BACKGROUND: Ischaemic nephropathy is currently a major public health issue in atherosclerotic populations. Although atherosclerotic cardiovascular disease in Asia has reached epidemic proportions over the last two decades, there is little published data on the prevalence of atherosclerotic renal artery stenosis (ARAS) in Oriental subjects. Because ARAS may be clinically silent until end-stage renal failure sets in, it is important to identify patients with significant but clinically unsuspected ARAS. ARAS and coronary artery disease (CAD) often coexist. AIMS: The purpose of the present study was to evaluate the prevalence and predictors of ARAS among Chinese patients with CAD. METHODS: A total of 230 consecutive Chinese patients with CAD confirmed by coronary angiography underwent an abdominal aortogram in the same sitting to screen for ARAS. Patient demographics and comorbidities were analysed for any association with ARAS. RESULTS: A total of 34 (14.8%) patients was found to have significant ARAS. Age and multivessel CAD were independent predictors of ARAS. Hypertension, renal insufficiency, extracranial cerebrovascular disease and female gender were also associated with a higher risk of ARAS but did not independently predict ARAS. CONCLUSION: Clinically silent yet angiographically significant ARAS is common among CAD patients. The prevalence and predictors of ARAS among Chinese patients with CAD are similar to those reported for Caucasian subjects. Underlying ARAS should be suspected in CAD patients with such comorbidities as hypertension, renal insufficiency, extracranial cerebrovascular disease, and more so in the elderly and those with multivessel disease.
FLASH is a protein recently shown to interact with the death effector domain of caspase-8 and is likely to be a component of the death-inducing signaling complex in receptor-mediated apoptosis. Here we show that antisense oligonucleotide-induced inhibition of FLASH expression abolished TNF-alpha-induced activation of NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-kappaB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6. TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore, serial deletion mapping demonstrated that a domain spanning the residues 856-1191 of FLASH activated NF-kappaB as efficiently as the full-length and could directly bind to TRAF2 in vitro and in the transfected cells. Taken together, these results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling.
To elucidate the role of endogenous transforming growth factor (TGF)-beta2 on human osteoblast cell, antisense phosphorothioate oligonucleotides (S-ODNs) complementary to regions in mRNA of TGF-beta2 were synthesized and examined their effects on TGF-beta2 production and cell proliferation in a human osteoblast cell line ROS 17/2. Antisense S-ODNs were designated for three different target regions in the mRNA of TGF-beta2. Among several antisense S-ODN analyzed, an oligonucleotide (AS-11) complementary to the translation initiation site of mRNA of TGF-beta2 demonstrated a selective and strong inhibitory effect on TGF-beta2 production in osteoblast cells. Other antisense S-ODNs which were designated for other regions in mRNA of TGF-beta2 and one- or three-base mismatched analogs of AS-11 showed little or much less antisense activities than AS-11. Therefore, the most effective target site in mRNA of TGF-beta2 is at the initiation codon region. The antisense effects of AS-11 were observed without reduction of levels of mRNA of TGF-beta2. Furthermore, the inhibition of TGF-beta2 expression by antisense S-ODN appeared to enhance cell proliferation, demonstrating the growth inhibitory effect of autocrine TGF-beta2 in osteoblast cells.
OBJECTIVE: To clarify the value of endotoxin concentrations in expressed prostatic secretions (EPS) in the diagnosis and classification of chronic prostatitis. PATIENTS, SUBJECTS AND METHODS: The study included 88 consecutive patients with chronic prostatitis and 15 controls with no urological disease. The diagnosis and classification were based on a history, symptoms, a digital rectal examination of the prostate, and a white blood cell count in the EPS. Endotoxin concentrations in the EPS or urine were measured using a colorimetric assay and standard microbiological methods used to identify bacterial growth. RESULTS: In men with chronic prostatitis caused by Gram-negative or combined Gram-negative and -positive bacteria, the endotoxin levels in urine collected immediately after prostatic massage were significantly greater (P < 0.01) than in a midstream urine sample, and the concentration in the EPS was significantly higher (P < 0.05) than that in the control group. The same was true of patients with chronic prostatitis and Gram-positive bacteria isolated from the EPS or urine after massage. In patients with chronic pelvic pain syndrome (grade IIIA) the endotoxin level in the urine after massage was also significantly higher (P < 0.05) than that of the midstream sample, but there was no significant difference between the concentration in these samples in patients with grade IIIB, and no significant difference between the endotoxin concentration of the EPS in patients with grade IIIB and that in controls. CONCLUSION: Endotoxin concentrations are increased in the EPS or urine (after prostatic massage) of men with bacterial chronic prostatitis or chronic pelvic pain syndrome grade IIIA. The current routine examinations (including bacterial culture and routine examination of EPS or urine) before diagnosis and classification of chronic prostatitis are insufficient to describe the cause and pathogenesis of this condition. The endotoxin concentration of the EPS or urine after massage may provide a supplementary tool to identify the cause of chronic prostatitis.
AIM: To clarify whether there are anatomical changes in tunica albuginea and corpora cavemosa in aged rats. METHODS: Seventeen male Sprague-Dawley rats were divided into three groups based on age. Group A consisted of young rats (9 weeks), Group B, middle aged rats (14 weeks) and Group C, old rats (62 weeks). The penile samples were obtained and observed under a scanning electron microscope. RESULTS: The thickness (mean +/- SD) of the tunica albuginea was 0.14 +/- 0.02, 0.16 +/- 0.03 and 0.06 +/- 0.02 mm in Groups A, B and C, respectively. The tunica albuginea of group C was significantly thinner than those of the other two groups (P < 0.05) and the elastic fibers were diminished in the old rats. In the corpora cavernosa of old rats, the intracavernous pillars were irregular, in which many large collagen fibers could be observed, and the smooth muscle and elastic fibers were reduced. CONCLUSION: In old rats, the tunica albuginea became thinner with diminished elastic fibers; the collagen fibers of corpora cavernosa were increased while the smooth muscle and elastic fibers were reduced.
OBJECTIVE: To prospectively evaluate the clinical applications of intravascular ultrasound (IVUS). METHODS: Four hundred and thirty seven patients with coronary artery disease (CAD) or suspect CAD were imaged with CAD and IVUS, including (1) assessment IVUS in 135 cases with normal coronary angiography (CAG) (2) comparison IVUS with CAG pre and after angioplasty in 52 patients with CAD (3) assessment of detecting calcification lesions with CAG and IVUS in 150 patients (4) predicting the cardiac events after stent implantation guided by IVUS (n = 47) and CAG (N = 53). RESULTS: IVUS may detect coronary atherosclerosis lesions with normal by CAG. CAG overestimated effect of angioplasty. IVUS was more accurate to determine effect and complications of PTCA compared with CAG. IVUS interpreted the mechanism of vessel dilatation in PTCA. The cardiac events after stent implantation were significantly reduced after IVUS examination as compared with CAG. CONCLUSIONS: IVUS represents a radically different approach to vascular anatomy. Unlike angiography, which displays the coronary artery as a silhouette of the contrast-filled lumen, IVUS generates a cross-sectional tomographic image of the lumen and vessel wall. IVUS plays an important role as a guidance in cardiac intervention.
Osteoblasts are the cells which form bone under the regulation not only by hormones and cytokines but also by ECM molecules via their attachment. To obtain insights into the role of intracellular signaling molecules operating to mediate the attachment-related regulation of osteoblastic functions, we investigated in osteoblast-like MC3T3E1 cells the effects of the overexpression of CIZ, a novel signaling protein which interacts with p130Cas. In MC3T3E1 cells, CIZ mRNA is expressed constitutively. Endogenous CIZ was localized in the MC3T3E1 cells with relatively high levels of accumulation at the attachment sites when the cells were cultured on fibronectin, collagen, or BSA. CIZ overexpression increased the number of adhesion plaques and reduced proliferation of the cells compared to that of control cells transfected with an empty vector. Furthermore, CIZ overexpression enhanced type I collagen mRNA expression, the most abundant constituent of bone matrix and a major product of osteoblasts. Analysis of the promoter region of type I collagen gene identified the presence of a consensus CIZ-binding sequence, which indeed conferred responsiveness to CIZ overexpression to a heterologous promoter. These data indicate that CIZ acts as a novel regulatory molecule in controlling osteoblastic function.
OBJECTIVE: To clarify the effects of androgens (testosterone and dihydrotestosterone, DHT) and ageing on gene expression of vasoactive intestinal polypeptide (VIP), assessed as the expression of VIP mRNA, in rat corpus cavernosum. Materials and methods The study comprised 160 male Sprague Dawley rats divided into group A (56 rats, 5 weeks old), group B (50 rats, 10 weeks old) and group C (54 rats, 58 weeks old). Groups A-C were subdivided, respectively, into subgroups 1 (intact controls), 2 (castrated), 3 (castrated but given testosterone undecanoate 25 mg/kg per month by intramuscular injection), 4 (castrated with testosterone undecanoate 50 mg/kg per month) and 5 (treated with finasteride 4.5 mg/kg per day, orally). At 4 and 10 weeks after these treatments half the rats were killed. Serum samples were taken for the measurement of total and free testosterone and DHT, using a radioimmunoassay. Penile samples (corpus cavernosum) were frozen in liquid nitrogen and stored at -80 degrees C. VIP mRNA was estimated using a semi-quantitative reverse-transcription polymerase chain reaction. RESULTS: There was no significant difference in VIP mRNA in rat corpus cavernosum between intact control and castrated subgroups, or subgroups treated with finasteride, in groups A-C, including both the 4- and 10-week old animals (P > 0.05). Penile VIP mRNA was unchanged at any dose of testosterone in the castrated subgroups in all groups (P > 0.05). There was no significant relationship between penile VIP mRNA and ageing (P > 0.05). CONCLUSIONS: The gene expression of VIP in rat corpus cavernosum is independent of androgens (testosterone and DHT) and ageing. Androgens probably induce penile erection by pathways other than VIP; ageing may have little effect on penile VIP mRNA.
Percutaneous transluminal coronary angioplasty (PTCA) of chronic total occlusions may be technically difficult and the success rate is limited despite increasing operator experience and improvements in PTCA hardware. The number of guidewires required to cross totally occluded lesions is higher than that for stenotic lesions. The ChoICE polymer-tip (PT) wire (Boston Scientific/Scimed, Inc., Maple Grove, Minnesota) is a relatively new stainless-steel core wire with a hydrophilic-coated polyurethane tip. Though never described in the literature, we found that the distal 4 cm of the wire can be cut and reshaped according to the operator's needs. Thus, instead of reshaping a kinked tip or using another new wire, the former being time-consuming and the latter expensive, one can simply cut off the kinked tip and start again with a "new wire." As the tip is resected, the wire becomes progressively more "intermediate-like" and "standard-like." We report our experience with the ChoICE PT wire in 50 consecutive cases of chronic total occlusions. The cumulative crossing success rates were 13/50 (26%) before any resections, 24/50 (48%) after 1 resection, 41/50 (82%) after 2 resections and 42/50 (84%) after 3 resections. There were no perforations, deaths, myocardial infarctions or need for bypass surgery. Our findings suggest that successful recanalization of chronic total occlusions can be achieved with a high success rate using the ChoICE PT wire. A strategy of progressively resecting the more floppy and kinked distal end can provide multiple uses from a single wire, optimizing recanalization success and obviating the need for additional wires.
Four types of phosphorothioate antisense oligonucleotides for transforming growth factor-beta 2 were synthesized and tested for their antisense activity in U937 cells. The full-length phosphorothioate modified antisense analogues exhibited the highest inhibitory effects on the transforming growth factor-beta 2 expression in U937 cells.
Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.