Biomedical subjects
Publications and source records attributed to J Jia.
Wilms' tumour (nephroblastoma) is a renal tumour that develops in childhood; it is one of the most common malignant tumours in children under 5 years old. Bone metastases are extremely rare in Wilms' tumour. Reported here is a patient who underwent nephrectomy for Wilms' tumour at the age of 2 years and presented with a jawbone mass in her left mandible 9 months later.
The Hedgehog (Hh) family of secreted proteins plays essential roles in a myriad of developmental processes via a complex signaling cascade conserved in species ranging from insects to mammals. In many developmental contexts, Hh acts as long-range morphogen to control distinct cellular outcomes as a function of its concentration. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal with an emphasis on the intracellular signaling cascade from the receptor to the nuclear effector. We discuss how graded Hh signals are transduced to govern distinct developmental outcomes.
Lifestyle exposures including cigarette smoke, alcohol, and caffeine have all been studied in relationship to male reproductive health. Over the years the focus has primarily been on semen quality and/or fertility. More recently, literature evaluating direct adverse effects of lifestyle exposures on sperm chromosomes and chromatin has grown due to concern that induced damage could be transmitted to offspring causing transgenerational health effects. In this paper we present a new analysis that summarizes published studies of smoking effects on sperm chromosome number and demonstrates a statistically significant increase in sperm disomy among smokers compared to nonsmokers (P < 0.001). In addition, new data on the effect of alcohol intake on sperm chromosome number are presented showing a rate ratio of 1.38 (95% CI 1.2, 1.6) for XY frequency in sperm of alcohol drinkers compared to nondrinkers.
The factors involved in maintenance and reversal of mean arterial blood pressure (MAP) in the chronic two-kidney one-clip hypertensive rat (2K1C-RHR) are still debated. The reduction in MAP after reversal of 2K1C hypertension has been ascribed either to release of a renal medullary depressor hormone (RMDH) or suppression of the renin-angiotensin and/or sympathetic nervous system. We studied in conscious rats: (i) The effects of angiotensin II receptor blockade (ARB; candesartan), sympathetic blockade (propranolol and phentolamine) or a combination on MAP in 6-week long 2K1C-RHR; (ii) The effects of reversal of 2K1C hypertension by removal of the constricting clip (unclipping, UC) or nephrectomy (Nx) on MAP, plasma renin activity (PRA) and noradrenaline (NA) spillover rates. The results show that: (i) MAP in the 2K1C-RHR was almost normalized by ARB but not significantly affected by the sympathetic blockade. The combination was not more effective than ARB alone; (ii) UC and Nx reduced MAP in 2K1C to similar levels as ARB. No significant changes in PRA or catecholamines could be detected in UC and Nx groups. We conclude that hypertension in 2K1C-RHR is maintained by the renin-angiotensin system without much contribution from the sympathetic nervous system. Furthermore, we found no evidence that UC of our model of 2K1C was associated with a generalized decrease in sympathetic tone or substantial release of RMDH from the unclipped kidney. Thus, we conclude that in the present model of 2K1C, both maintenance and reversal of hypertension are controlled by the renin-angiotensin system.
Oral contraceptives (OC) are a risk factor for female genital cancers and in vivo studies have shown that progestins stimulate human papillomavirus (HPV) gene expression. A similar role for hormone replacement therapy (HRT) has received little evaluation. Cervical/vaginal specimens were obtained to detect HPV from postmenopausal women (n = 429) seeking annual gynaecologic care. HPV was detected in 14% of women and 4.4% had high-risk, oncogenic types. HPV prevalence was similar across current, past and never HRT users. After adjustment for HPV-related risk factors, current and past user status showed no increased viral detection compared with never users. HRT duration also did not elevate risk among current users. However, longer duration (adj. OR 1.5/year, 95% CI 1.0-2.3) and longer latency (adj. OR 1.2/year, 95% CI 0.9-1.7) among past users of oestrogen/progestin regimens were associated with greater risk. Overall use of HRTs was not associated with HPV detection or disease. However, past users of combination HRTs had significantly greater risk of HPV detection with longer HRT duration and latency, similar to OC-HPV findings. The recommendation that postmenopausal women continue HRTs long term may lead to an increased development of HPV-related diseases, of particular concern among those who discontinue HRTs and subsequent gynaecologic care for early cancer detection.
Grancalcin is a cytosolic Ca(2+)-binding protein originally identified in human neutrophils. It belongs to a new class of EF-hand proteins, called PEF proteins, which contain five EF-hand motifs. At the N-terminus of grancalcin there is a approximately 50 residue-long segment rich in glycines and prolines. The fifth EF-hand, unpaired within the monomer, provides a means for dimerization through pairing with its counterpart in a second molecule. The structure of full-length grancalcin in the apo form and with one EF3 within the dimer occupied by a Ca(2+) ion have been determined. Although the N-terminal segment was present in the molecule, this part was disordered in the crystals. Here, the structure of a truncated form of grancalcin, which is lacking 52 N-terminal residues, in the presence and absence of Ca(2+) is presented. In the Ca(2+)-bound form the ions are found in the EF1 and EF3 hands. Binding of Ca(2+) to these two EF hands produces only minor conformational changes, mostly within the EF1 Ca(2+)-binding loop. This observation supports the hypothesis, formulated on the basis of the structure of a homologous protein ALG-2 which shows significant differences in the orientation of EF4 and EF5 compared with grancalcin, that calcium is a necessary factor but not sufficient alone for inducing a significant conformational change in PEF proteins.
OBJECTIVE: To study the relation between infection of Helicobacter pylori strains expressing CagA and upper gastrointestinal diseases, and to assess the change of anti-CagA IgG antibody levels after eradication of H. pylori. METHODS: Gastric biopsy was conducted among eight hundred and eight patients who received endoscopy to determine the pathological changes of mucosa and infectious status of H. pylori. The presence of serum anti-CagA IgG was detected in each H. pylori-positive patient by ELISA. Eradication therapy by PPI was conducted to the H. pylori-positive individuals. The anti-CagA IgG levels were reexamined among 60 patients whose H. pylori infection failed to be eradicated and 120 patients whose H. pylori infection was successfully eradicated after 3 months and 6 months. RESULTS: The serum anti-CagA IgG-positive rates were 55.4%, 70.5%, 83.2%, 90.8% and 89.7% in H. pylori-positive patients with chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), gastric ulcer (GU), duodenal ulcer (DU), and gastric cancer (GC) respectively. The serum anti-CagA IgG-positive rates among the latter 4 groups were significantly higher than that in CSG group, and the serum anti-CagA IgG-positive rates among the latter 3 groups were significantly higher than that in CAG group. The serum anti-CagA IgG-positive rate among patients with CAG was significantly higher than that among patients with CSG (P < 0.05). The CagA-positive rates in the groups of intestinal metaplasia (IM), atypical hyperplasia and GC were significantly higher than those in the groups of CSG and CAG (P < 0.05). By the end of 3 and 6 months after the eradication therapy, the antibody level had decreased from a mean value of (69 +/- 38) U/ml to (47 +/- 30) U/ml and (32 +/- 15) U/ml among 120 patients with successful eradication and the serum antibody reverted to negative only in 23 cases from them. There was no significant change in serum anti-CagA IgG level among 60 patients without successful eradication. CONCLUSION: Infection with CagA-positive H. pylori strains is associated with an increased risk of developing more severe gastroduodenal diseases and more severe gastric mucosa lesions. Despite an overall significant decrease of anti-CagA IgG level in sera after H. pylori eradication, this serological method cannot be used to monitor individual treatment effect because the anti-CagA IgG level decreases slowly.
Degradation of 29 dyes by means of an activated carbon fiber (ACF) electrode electrolysis system was performed successfully. Almost all dye solutions tested were decolorized effectively in this ACF electrolysis process. Internal relationships between treatment mechanisms and chemical composition of the dye have been discussed in this paper. Generally, it is shown that higher solubility leads to greater degradation in the process. Dyes with many -SO3-, COO-, -SO2NH2, -OH, hydrophilic groups, and azo linkages are susceptible to reduction. However, dyes with many -C=O, -NH-and aromatic groups, and hydrophobic groups, tend to be adsorbed. For dyes with -SO3-, COOH and -OH groups, if their molecules linearly spread in solution and have a significant tendency to form colloids by hydrogenous bonding, they also tend to be adsorbed and flocculated. Typical dynamic electrolysis of dye Acid Red B, Vat Blue BO and Disperse Red E-4B shows how the two major mechanisms, degradation and adsorption, act differently during treatment. Reduction occurs evenly during treatment. During the dominant adsorption process, after certain amount of iron is generated, colloid precipitation occurs and TOC and color are rapidly removed.
BACKGROUND: The Ca2+ binding apoptosis-linked gene-2 (ALG-2) protein acts as a proapoptotic factor in a variety of cell lines and is required either downstream or independently of caspases for apoptosis to occur. ALG-2 belongs to the penta-EF-hand (PEF) protein family and has two high-affinity and one low-affinity Ca2+ binding sites. Like other PEF proteins, its N terminus contains a Gly/Pro-rich segment. Ca2+ binding is required for the interaction with the target protein, ALG-2 interacting protein 1 (AIP1). RESULTS: We present the 2.3 A resolution crystal structure of Ca2+-Ioaded des1-20ALG-2 (aa 21-191), which was obtained by limited proteolysis of recombinant ALG-2 with elastase. The molecule contains eight alpha helices that fold into five EF-hands, and, similar to other members of this protein family, the molecule forms dimers. Ca2+ ions bind to EF1, EF3, and, surprisingly, to EF5. In the related proteins calpain and grancalcin, the EF5 does not bind Ca2+ and is thought to primarily facilitate dimerization. Most importantly, the conformation of des1-20ALG-2 is significantly different from that of calpain and grancalcin. This difference can be described as a rigid body rotation of EF1-2 relative to EF4-5 and the dimer interface, with a hinge within the EF3 loop. An electron density, which is interpreted as a hydrophobic Gly/Pro-rich decapeptide that is possibly derived from the cleaved N terminus, was found in a hydrophobic cleft between these two halves of the molecule. CONCLUSIONS: A different relative orientation of the N- and C-terminal halves of des1-20ALG-2 in the presence of Ca2+ and the peptide as compared to other Ca2+loaded PEF proteins changes substantially the shape of the molecule, exposing a hydrophobic patch on the surface for peptide binding and a large cleft near the dimer interface. We postulate that the binding of a Gly/ Pro-rich peptide in the presence of Ca2+ induces a conformational rearrangement in ALG-2, and that this mechanism is common to other PEF proteins.
Human trpS gene was cloned into the expression vector pET-24a(+) to yield pET-24a(+)-HTrpRS, which could direct the synthesis of a mammalian derived protein in Escherichia coli BL21-CodonPlus(DE3)-RIL. The vector allows overproduction and single-step purification of His(6)-tagged human tryptophanyl-tRNA synthetase by the facilitation of metal (Ni(2+)) chelate affinity chromatography. The expression level of human TrpRS was about 40% of total cell proteins after isopropyl beta-D-thiogalactoside induction. The overproduced human TrpRS-His(6) could be purified to homogeneity within 2 h and about 24 mg purified enzyme could be obtained from 400 ml cell culture. The His(6) tag at C terminus had little effect on the binding ability of its substrates.
The aim of this study was to explore the possibilities of non-surgical management for superficial carcinomas of the oesophagus and gastric cardia. Thirty-one patients with superficial oesophageal or gastric cardiac carcinomas, who refused or were unsuitable for surgery, received endoscopic Nd:YAG laser therapy combined with local injection of chemotherapeutic drugs 5-fluorouracil and mitomycin. After one to four sessions of treatment no cancer cells were detected by multiple biopsies and no complications such as bleeding or perforation occurred in any case. The 31 patients have been followed-up for 25-91 months (five cases for 91 months, eight cases for 79 months, four cases for 55 months, eight cases for 33 months and six cases for 25-31 months). All patients are surviving without sign of recurrence and no cancer cells were detected by endoscopic biopsies. Our findings indicate that this is an effective and safe therapeutic modality and may be considered as the first choice for those patients who refuse or are not suitable for surgery, and for those of older age and in poor condition.
A mathematical model describing the transient temperature distribution of grain in a cylindrical storage bin with mixed boundaries is presented and solved using the finite element method. Using the typical meteorological data of a region such as temperate China, temperature changes of wheat in a storage bin are simulated and analysed in detail. Simulated results indicate that high temperature accumulation areas of the grain are in the bin centre and near the bin bottom or at the top surface of the grain throughout the whole year and ventilation under appropriate weather conditions is necessary. This method can be used to develop and evaluate aeration control strategy and reduce the need for chemical treatments of grain during storage.
The roles of invariant residues at the active site of transaldolase B from Escherichia coli have been probed by site-directed mutagenesis. The mutant enzymes D17A, N35A, E96A, T156A, and S176A were purified from a talB-deficient host and analyzed with respect to their 3D structure and kinetic behavior. X-ray analysis showed that side chain replacement did not induce unanticipated structural changes in the mutant enzymes. Three mutations, N35A, E96A, and T156A resulted mainly in an effect on apparent kcat, with little changes in apparent Km values for the substrates. Residues N35 and T156 are involved in the positioning of a catalytic water molecule at the active site and the side chain of E96 participates in concert with this water molecule in proton transfer during catalysis. Substitution of Ser176 by alanine resulted in a mutant enzyme with 2.5% residual activity. The apparent Km value for the donor substrate, fructose 6-phosphate, was increased nearly fivefold while the apparent Km value for the acceptor substrate, erythrose 4-phosphate remained unchanged, consistent with a function for S176 in the binding of the C1 hydroxyl group of the donor substrate. The mutant D17A showed a 300-fold decrease in kcat, and a fivefold increase in the apparent Km value for the acceptor substrate erythrose 4-phosphate, suggesting a role of this residue in carbon-carbon bond cleavage and stabilization of the carbanion/enamine intermediate.
BACKGROUND: Restoring renal perfusion pressure (unclipping) of one-kidney-one-clip renal hypertensive (1 K1C) rats normalizes mean arterial pressure (MAP) rapidly. This has been attributed to salt/volume losses or release of the putative renal medullary depressor hormone (RMDH). OBJECTIVE: To investigate the effects of endothelin receptor A and B (ET(A)/ET(B)) antagonism on unclipping. DESIGN AND METHODS: Telemetric devices were implanted in male Wistar 1K1C rats for measurement of conscious MAP. Hypertension was reversed by unclipping with the animal under brief anaesthesia. Seven rats were treated with the ET(A)/ET(B) antagonist, TAK-044 (two doses of 10 mg/kg intraperitoneally in 24 h), and eight rats received its vehicle. In order to investigate whether endothelin receptor antagonism could release RMDH under resting conditions, TAK-044 was administered to telemetered non-clipped intact and chemically renal medullectomized rats (BEA treatment). RESULTS: TAK-044 did not affect resting MAP, urine flow or sodium excretion in 1K1C rats. However, after unclipping, the TAK-044-treated group showed a more marked reduction in MAP during the first 24 h after unclipping (P< 0.01). TAK-044 also reduced urine flow and sodium excretion during the first 8 h after unclipping (P< 0.05). TAK-044 reduced resting MAP (P< 0.05) to a similar extent in intact and BEA rats. CONCLUSIONS: TAK-044 potentiated the reduction in MAP after unclipping, independently of changes in urine flow and sodium excretion. It also reduced MAP in normotensive rats--an effect that was not dependent on an intact renal medulla. Potentiation of the depressor response to unclipping by TAK-044 could be the result of an interaction of endogenous endothelin receptors with renal depressor mechanisms--possibly, the release, actions, or both, of the putative RMDH.
OBJECTIVE: We studied endothelial nitric oxide synthase (eNOS) expression in the kidneys of two-kidney, one-clip renal hypertensive rats (2K1C) before and after removal of the clip (unclipping, UC). We hypothesised that the haemodynamic changes induced by 2K1C and UC would change eNOS expression in the two kidneys. METHODS: Six weeks after inducing 2K1C, mean arterial pressure (MAP) was measured in conscious rats and hypertension reversed by UC. Left and right kidney eNOS protein in cortex and outer medulla was semi-quantified using immunoblotting. Groups were; normotensive (n = 10), 2K1C (n = 10), 3 h (n = 10), 48 h (n = 7) and 4 weeks (n = 7) after UC. The effect of 7 days of aldosterone or angiotensin II (Ang II) infusion on medullary eNOS protein was tested as well as the effect of L-NAME (nitric oxide (NO) synthase inhibitor) on medullary blood flow (MBF) in anaesthetized 2K1C. RESULTS: UC reduced MAP from 178 +/- 5 to 134 +/- 3 mmHg after 3 h and normalized MAP at 48 h and 4 weeks. The medulla from 2K1C kidneys contained about 33% less eNOS protein compared with normotensive kidneys (P < 0.05). This difference was still evident at 3 h (P < 0.05), but completely reversed at 48 h and 4 weeks after UC. Similar levels of eNOS expression were seen in the left and right kidney at all time points. Cortical eNOS was increased in kidneys from 2K1C. Neither Ang II nor aldosterone affected eNOS expression in the medulla. MBF was under similar influence of NO in 2K1C compared with normotensive kidneys. CONCLUSIONS: 2K1C is associated with reduced levels of eNOS protein in the renal medulla of both clipped and contralateral kidney. eNOS expression in right and left kidney was not changed despite expected large changes in haemodynamics of the two kidneys. The reduced level of eNOS may be associated with a reduction in MBF and thus be of patho-physiological importance in renovascular hypertension.
High-affinity glycine transport in neurons and glial cells is a primary means of inactivating synaptic glycine. We have synthesized a potent selective inhibitor of glycine transporter 1 (GlyT1), and characterized its activity using a quail fibroblast cell line (QT6). The glycine transporters GlyT1A, GlyT1B, GlyT1C, and GlyT2 were stably expressed in QT6 cells. The transporters expressed in these cells exhibited appropriate characteristics as described previously for these genes: Na(+)/Cl(-) dependence, appropriate K(m) values for glycine uptake, and appropriate pharmacology, as defined in part by the ability of N-methyl glycine (sarcosine) to competitively inhibit glycine transport. Furthermore, the characteristics of the transporters in the cell lines recapitulate the characteristics of glycine transporters observed in tissue preparations. We developed a sarcosine derivative, (R)-(N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (ALX 5407), and examined its activity against the cloned glycine transporters. ALX 5407 completely inhibited glycine transport in the GlyT1 cells, with an IC(50) value of 3 nM, but had little or no activity at the human GlyT2 transporter, at other binding sites for glycine, or at other neurotransmitter transporters. The inhibition of glycine transport was essentially irreversible. ALX 5407 represents a novel tool in the investigation of N-methyl-D-aspartate-receptor function. This class of drug may lead to novel therapies in the treatment of schizophrenia.
Grancalcin is a Ca(2+)-binding protein expressed at high level in neutrophils. It belongs to the PEF family, proteins containing five EF-hand motifs and which are known to associate with membranes in Ca(2+)-dependent manner. Prototypic members of this family are Ca(2+)-binding domains of calpain. Our recent finding that grancalcin interacts with L-plastin, a protein known to have actin bundling activity, suggests that grancalcin may play a role in regulation of adherence and migration of neutrophils. The structure of human grancalcin has been determined at 1.9 A resolution in the absence of calcium (R-factor of 0.212 and R-free of 0.249) and at 2. 5 A resolution in the presence of calcium (R-factor of 0.226 and R-free of 0.281). The molecule is predominantly alpha-helical: it contains eight alpha-helices and only two short stretches of two-stranded beta-sheets between the loops of paired EF-hands. Grancalcin forms dimers through the association of the unpaired EF5 hands in a manner similar to that observed in calpain, confirming this mode of association as a paradigm for the PEF family. Only one Ca(2+) was found per dimer under crystallization conditions that included CaCl(2). This cation binds to EF3 in one molecule, while this site in the second molecule of the dimer is unoccupied. This unoccupied site shows higher mobility. The structure determined in the presence of calcium, although does not represent a fully Ca(2+)-loaded form, suggests that calcium induces rather small conformational rearrangements. Comparison with calpain suggests further that the relatively small magnitude of conformational changes invoked by calcium alone may be a characteristic feature of the PEF family. Moreover, the largest differences are localized to the EF1, thus supporting the notion that calcium signaling occurs through this portion of the molecule and that it may involve the N-terminal Gly/Pro rich segment. Electrostatic potential distribution shows significant differences between grancalcin and calpain domain VI demonstrating their distinct character.
The gene encoding endopolygalacturonase (EC 3.2.1.15) has been cloned, sequenced and expressed from three strains of Saccharomyces cerevisiae (including nonsecretors) and three strains of Kluyveromyces marxianus. Both control and coding regions showed small differences within each species, one including loss of a potential glycosylation site. Two non-secreting S. cerevisiae strains (FY1679 and var. uvarum) had non-transcribed copies of functional genes. Maximum enzyme activity was achieved with the S. cerevisiae FY1679 gene in an expressing vector, with an enzyme activity of 51 micromol of reducing sugar released from polygalacturonic acid microg protein(-1) min(-1), the highest so far reported for a yeast.