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Biomedical subjects

S Zhang

Publications and source records attributed to S Zhang.

At least 199 records · Page 11Linked to original sources

Redox regulation of endothelial barrier integrity.

Intestinal ischemia-reperfusion is associated with the generation of reactive oxygen metabolites as well as remote, oxidant-mediated lung injury. Oxidants elicit endothelial redox imbalance and loss of vascular integrity by disorganizing several junctional proteins that contribute to the maintenance and regulation of the endothelial barrier. To determine the specific effect of redox imbalance on pulmonary vascular barrier integrity, microvascular permeability was determined in lungs of animals subjected to chemically induced redox imbalance. The effect of redox imbalance on microvascular permeability and endothelial junctional integrity in cultured lung microvascular cells was also determined. Whole lung and cultured pulmonary endothelial cell permeability both increased significantly in response to chemical redox imbalance. Thiol depletion also resulted in decreased endothelial cadherin content and disruption of the endothelial barrier. These deleterious effects of intracellular redox imbalance were blocked by pretreatment with exogenous glutathione. The results of this study suggest that redox imbalance contributes to pulmonary microvascular dysfunction by altering the content and/or spatial distribution of endothelial junctional proteins.

Animals↗

Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus.

The pharmacokinetics of mycophenolic acid (MPA) was studied after oral administration of mycophenolate mofetil (MMF) in 8 liver transplant patients. The mean (+/- SD) maximum MPA plasma concentration of 10.6 (+/- 7.5) mg/ml was achieved within 0.5 to 5 hours. The mean (+/- SD) steady-state area under the plasma concentration versus time curve (AUC(0-12)) was 40 (+/- 30.9) mg/ml/h. The mean (+/- SD) half-life was 5.8 (+/- 3.8) hours. There was poor correlation between trough blood concentrations of tacrolimus (r = -0.004) or serum creatinine (r = 0.689) with MPA AUC, while the serum bilirubin concentrations correlated (r = 0.743) well with MPA AUC, suggesting impairment in MPA conjugation in patients with liver dysfunction. The mean (+/- SD) ratio of the AUC of mycophenolic acid glucuronide (MPAG) to MPA was 64 (+/- 84), which correlated significantly with serum creatinine (r = 0.72) but not with serum bilirubin concentrations (r = 0.309), indicating accumulation of MPAG in patients with renal dysfunction. In 7 primary liver transplant patients on the same dose of MMF, the trough plasma concentrations of MPA during the first week of therapy ranged from < 0.3 to 1.5 microg/ml. The MPA concentrations increased by several folds during the next few weeks, which correlates well with increases in serum albumin concentrations. Changes in albumin appear to partially contribute to the variations in the pharmacokinetics of MPA in liver transplant patients.

Adult↗

Rho kinases play an obligatory role in vertebrate embryonic organogenesis.

Rho-associated kinases (Rho kinases), which are downstream effectors of RhoA GTPase, regulate diverse cellular functions including actin cytoskeletal organization. We have demonstrated that Rho kinases also direct the early stages of chick and mouse embryonic morphogenesis. We observed that Rho kinase transcripts were enriched in cardiac mesoderm, lateral plate mesoderm and the neural plate. Treatment of neurulating embryos with Y27632, a specific inhibitor of Rho kinases, blocked migration and fusion of the bilateral heart primordia, formation of the brain and neural tube, caudalward movement of Hensen's node, and establishment of normal left-right asymmetry. Moreover, Y27632 induced precocious expression of cardiac alpha-actin, an early marker of cardiomyocyte differentiation, coincident with the upregulated expression of serum response factor and GATA4. In addition, specific antisense oligonucleotides significantly diminished Rho kinase mRNA levels and replicated many of the teratologies induced by Y27632. Thus, our study reveals new biological functions for Rho kinases in regulating major morphogenetic events during early chick and mouse development.

Amides↗

Induced repatterning of type XVIII collagen expression in ureter bud from kidney to lung type: association with sonic hedgehog and ectopic surfactant protein C.

Epithelial-mesenchymal tissue interactions regulate the formation of signaling centers that play a role in the coordination of organogenesis, but it is not clear how their activity leads to differences in organogenesis. We report that type XVIII collagen, which contains both a frizzled and an endostatin domain, is expressed throughout the respective epithelial bud at the initiation of lung and kidney organogenesis. It becomes localized to the epithelial tips in the lung during the early stages of epithelial branching, while its expression in the kidney is confined to the epithelial stalk region and is lost from the nearly formed ureter tips, thus displaying the reverse pattern to that in the lung. In recombinants, between ureter bud and lung mesenchyme, type XVIII collagen expression pattern in the ureter bud shifts from the kidney to the lung type, accompanied by a shift in sonic hedgehog expression in the epithelium. The lung mesenchyme is also sufficient to induce ectopic lung surfactant protein C expression in the ureter bud. Moreover, the shift in type XVIII collagen expression is associated with changes in ureter development, thus resembling aspects of early lung type epigenesis in the recombinants. Respecification of collagen is necessary for the repatterning process, as type XVIII collagen antibody blocking had no effect on ureter development in the intact kidney, whereas it reduced the number of epithelial tips in the lung and completely blocked ureter development with lung mesenchyme. Type XVIII collagen antibody blocking also led to a notable reduction in the expression of Wnt2, which is expressed in the lung mesenchyme but not in that of the kidney, suggesting a regulatory interaction between this collagen and Wnt2. Respecification also occurred in a chimeric organ containing the ureter bud and both kidney and lung mesenchymes, indicating that the epithelial tips can integrate the morphogenetic signals independently. A glial cell line-derived neurotrophic factor signal induces loss of type XVIII collagen from the ureter tips and renders the ureter bud competent for repatterning by lung mesenchyme-derived signals. Our data suggest that differential organ morphogenesis is regulated by an intra-organ patterning process that involves coordination between inductive signals and matrix molecules, such as type XVIII collagen.

Animals↗

Cloning and expression of L-asparaginase gene in Escherichia coli.

The L-asparaginase (ASN) from Escherichia coli AS1.357 was cloned as a DNA fragment generated using polymerase chain reaction technology and primers derived from conserved regions of published ASN gene sequences. Recombinant plasmid pASN containing ASN gene and expression vector pBV220 was transformed in different E. coli host strains. The activity and expression level of ASN in the engineering strains could reach 228 IU/mL of culture fluid and about 50% of the total soluble cell protein respectively, more than 40-fold the enzyme activity of the wild strain. The recombinant plasmid in E. coli AS1.357 remained stable after 72 h of cultivation and 5 h of heat induction without selective pressure. The ASN gene of E. coli AS1.357 was sequenced and had high homology compared to the reported data.

Asparaginase↗

Inactivation of the p16 gene in human pituitary nonfunctioning tumors by hypermethylation is more common in null cell adenomas.

Recent studies have shown that methylation of the CpG island within the p16/CDKN2A/MTS1 (p16) gene is associated with loss of expression of p16 protein in pituitary tumors. We analyzed a series of 21 pituitary adenomas and three normal pituitaries along with a human pituitary cell line (HP75) for methylation of exon 1 by methylation-specific PCR, immunohistochemistry, and Western blotting. PCR analysis showed that 5/7 (71%) of null cell adenomas, but only 2/7 (29%) gonadotroph tumors were hypermethylated. In addition,1 of 2 ACTH tumors but no GH (n = 4) or PRL (n = 1) adenoma examined were hypermethylated. Immunostaining and Western blot analysis of protein expression supported the methylation-specific PCR analyses. These results show that p16 gene silencing by hypermethylation is more common in null cell adenomas compared to other nonfunctioning adenomas such as gonadotroph tumors and that the role of p16 in the pathogenesis of pituitary adenomas is restricted to specific tumor subtypes.

Adenoma↗

End-labeling of long DNA fragments with biotin and detection of DNA immobilized on magnetic beads.

To immobilize DNA fragments onto magnetic beads coated with streptavidin for isolation purpose, it is important to label one biotin molecule at one terminus of DNA fragment. After failure to label long DNA with biotin by PCR and filling-in reaction, a 9.2 kb DNA was labeled with biotin by a modified ligation strategy. A simple method is also reported to detect the quantity and integrity of DNA immobilized on the magnetic beads.

Base Sequence↗

Discontinuation of antihypertensive drugs due to adverse events: a systematic review and meta-analysis.

We conducted a systematic review of randomized, controlled, monotherapy trials since 1990 of oral antihypertensive agents in patients with essential hypertension. Our objective was to quantify the frequency of discontinuation of antihypertensive agents due to adverse events from a meta-analysis of the studies. A total of 190 studies met inclusion criteria. The highest frequency of discontinuations due to adverse events (DAEs) occurred with calcium channel blockers (6.7%) and alpha-adrenergic blockers (6.0%); the lowest with diuretics and angiotensin receptor blockers (each 3.1%). Only in calcium channel blocker studies was the frequency of DAEs greater in treated patients than in patients receiving placebo, but the difference was not significant. This systematic review suggests that the frequency of DAEs in monotherapy antihypertensive trials varies across drug classes and should be considered when choosing drugs for patients with essential hypertension.

Antihypertensive Agents↗

Landing strategies in honeybees, and possible applications to autonomous airborne vehicles.

Insects, being perhaps more reliant on image motion cues than mammals or higher vertebrates, are proving to be an excellent organism in which to investigate how information on optic flow is exploited to guide locomotion and navigation. This paper describes one example, illustrating how bees perform grazing landings on a flat surface. A smooth landing is achieved by a surprisingly simple and elegant strategy: image velocity is held constant as the surface is approached, thus automatically ensuring that flight speed is close to zero at touchdown. No explicit knowledge of flight speed or height above the ground is necessary. The feasibility of this landing strategy is tested by implementation in a robotic gantry, and its applicability to autonomous airborne vehicles is discussed.

Animals↗

Clinical outcomes in reduction mammaplasty: a systematic review and meta-analysis of published studies.

This systematic review and meta-analysis were undertaken to determine whether reduction mammaplasty improves measurable outcomes in women with breast hypertrophy. A systematic review of the literature in 5 languages from 1985 until March 1999 was performed, and data were compared for meta-analysis. Eligible studies were both experimental and observational and involved women with preoperative physical and/or psychosocial signs and symptoms who underwent reduction mammaplasty for breast hypertrophy. Outcomes assessed were postoperative physical signs and symptoms such as shoulder pain, shoulder (bra strap) grooving, and quality-of-life domains, such as physical and psychological functioning, and were expressed primarily as risk differences (RDs). Twenty-nine studies of 4173 patients met all eligibility criteria. Reduction mammaplasty was associated with a statistically significant improvement in physical signs and symptoms involving shoulder pain (RD, 0.71 [95% confidence interval (CI), 0.62-0.80]); shoulder grooving (RD, 0.69 [95% CI, 0.60-0.78]); upper/lower back pain (RD, 0.59 [95% CI, 0.48-0.70]); neck pain (RD, 0.50 [95% CI, 0.37-0.64]); intertrigo (RD, 0.44 [95% CI, 0.34-0.54]); breast pain (RD, 0.36 [95% CI, 0.17-0.55]); headache (RD, 0.28 [95% CI, 0.11-0.46]); and pain/numbness in the hands (RD, 0.11 [95% CI, 0.04-0.18]). The quality-of-life parameter of physical functioning was also statistically significant (RD, 0.58 [95% CI, 0.44-0.71]), while psychological functioning was not significant (RD, 0.46 [95% CI, 0.00-1.00]). The evidence suggests that women undergoing reduction mammaplasty for breast hypertrophy have significant postoperative improvement in preoperative signs and symptoms, quality of life, or both.

Adult↗

Concurrent babesiosis and ehrlichiosis in an elderly host.

An 85-year-old man, actively infected with Babesia microti and Ehrlichia chaffeensis, presented with fatigue and thrombocytopenia. He developed rhabdomyolysis and multiple organ failure, which led to death 6 days after initial presentation. To our knowledge, concurrent acute disease due to these 2 organisms has not been reported previously, although serologic studies have shown that some patients acquire both infections in life.

Aged↗

Ischemic colitis with atypical reactive changes that mimic dysplasia (pseudodysplasia).

OBJECTIVE: To describe reactive or reparative but atypical epithelial changes that occur in ischemic colitis. DESIGN: Surgical pathology files were searched for the diagnosis "ischemia, bowel." All cases were studied for reactive or reparative atypical changes. These were characterized and correlated with clinical information. RESULTS: Reactive atypical (pseudodysplastic) changes were found in 8 of 28 cases of ischemic bowel. The clinical history did not indicate ischemic colitis in 6 of 8 cases. In 3 cases, neutrophils in the lamina propria or acute cryptitis and crypt abscesses that suggested inflammatory bowel disease were noted. CONCLUSION: Ischemic changes in the bowel may produce reactive epithelial changes with sufficient atypia to simulate dysplasia. These may be associated with histologic changes that simulate inflammatory bowel disease, specifically ulcerative colitis. Since in most cases even the clinician is not sure whether the patient has ischemia or inflammatory bowel disease and because histologic changes of the latter may occur in ischemic bowel, there is a danger that the atypical reactive ischemic changes could be interpreted as true dysplasia that occurs in inflammatory bowel disease.

Aged↗

Conserved genetic findings in metastatic bladder cancer: a possible utility of allelic loss of chromosomes 9p21 and 17p13 in diagnosis.

CONTEXT: Molecular analysis of microsatellite alterations of biologically distinct tumor cell subpopulations from the same patient may aid in the determination of tumor origin and further our understanding of the genetic basis of cancer progression. DESIGN: The authors examined the pattern of allelic loss with polymorphic microsatellite markers on chromosome 9p21 (D9S161, D9S171, IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 locus, in matched primary and metastatic bladder cancers from 9 patients. All patients underwent cystectomy for bladder cancer and had regional lymph node metastases at the time of surgery. Genomic DNA was prepared from primary cancers and matched synchronous lymph node metastases using a microdissection method. RESULTS: The overall frequency of allelic loss was 78% in primary cancer and 89% in paired metastatic cancer. The frequency of allelic loss in the primary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and 80% with TP53. The frequency of allelic loss in matched metastatic cancer was 100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical pattern of allelic imbalance (allelic loss or retention) at multiple DNA loci was observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case showed allelic loss in the metastasis, but not in the primary cancer. CONCLUSIONS: The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53) was generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancer was conserved in paired metastatic carcinoma. These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.

Aged↗

[Study on polymorphism of D gene exons among RhD-negative Chinese Han population].

OBJECTIVE: To explore the genomic structure of 8 exons in D gene of RhD(-) Chinese Han population. METHODS: Polymerase chain reaction-sequence specific primers(PCR-SSP) were used to study genomic DNA from 50 samples of RhD(-) Chinese Han donors. Exons 2, 3, 4, 5, 6, 7, 9, 10 of RHD gene and exons 1, 2, 4, 5 of RHCE gene were specifically amplified, also intron 4 of them was amplified. RESULTS: Phenotypes of the 50 RhD(-) donors were: 22 ccdee, 22 Ccdee, 3 CcdEe, 3 CcdEe. The 8 exons of RHD gene were completely absent in 25 donors with ccdee or ccdEe phenotype, while polymorphisms of D gene exons were found in 25 donors with Ccdee or CcdEe phenotype: the presence of all 8 exons of D gene in 9 donors, the absence of the 8 exons in 7 donors, the presence of exon 2 in 5 donors, the presence of exon 6 in 3 donors and the presence of exons 2, 6, 10 in 1 donor were demonstrated. CONCLUSION: Polymorphisms of RHD gene exons were present among RhD(-) Chinese Han blood donors. The 8 exons of RHD gene were completely absent in donors with Rhesus cc phenotype, while 5 polymorphisms of RHD gene exons were found in donors with Rhesus Cc phenotype. The discrepancy of the RHD gene in RhD(-) individuals between Chinese Hans and Caucasians indicates that care should be exercised by clinicians in the use of the RhD genotyping results.

China↗

The relative contribution of mast cell subsets to conjunctival TH2-like cytokines.

PURPOSE: To investigate the distribution of the T-helper (TH)2-like cytokines, interleukin (IL)-4, IL-5, IL-6, and IL-13 between mast cell subsets in conjunctival biopsy specimens from normal subjects and those with seasonal allergic conjunctivitis (SAC) during and outside of the grass pollen season. METHODS: Sequential and double in situ hybridization (ISH) and immunohistochemistry (IHC) were performed on thin sections of human conjunctiva to determine the colocalization of the immunoreactivity of IL-4, IL-5, IL-6, and IL-13 to mast cell subsets in normal subjects and subjects with atopy and to detect IL-4 mRNA in conjunctival mast cells. RESULTS: More than 90% of IL-4+-immunoreactive cells were observed to be mast cells in conjunctival biopsy specimens from all patient groups. The majority of IL-5+, IL-6+, and IL-13+ cells were also noted to be mast cells for each group. IL-4 preferentially colocalized to the tryptase+-chymase+ mast cell phenotype (MC(TC)) with MC(TC) cells comprising 93.3% of cytokine+ mast cells in symptomatic SAC (P = 0.0017), 89.2% in asymptomatic SAC (P = 0.0008), and 77.8% in normal subjects (P = 0.0472). IL-13 appeared to colocalize preferentially to the MC(TC) phenotype and IL-5 and IL-6 to the MC(T) phenotype. ISH showed that 75.8% of mast cells in normal subjects, 78.7% in subjects with symptomatic SAC, and 18.7% in subjects with asymptomatic SAC expressed mRNA for IL-4. CONCLUSIONS: Conjunctival mast cells are an important source of IL-4, IL-5, IL-6, and IL-13 immunoreactivity, with preferential colocalization of IL-4 and IL-13 on the MC(TC) subset and IL-5 and IL-6 to the MC(T) subset. This evidence suggests that differences in protease phenotype may also reflect functional differences evidenced by the different patterns of cytokine distribution.

Adult↗

Preretinal neovascularization associated with acetazolamide-induced systemic acidosis in the neonatal rat.

PURPOSE: NH4Cl gavage in the neonatal rat produces a metabolic acidosis-induced retinopathy which serves as a model for retinopathy of prematurity (ROP). Acetazolamide induces a metabolic acidosis via an alternative biochemical mechanism (bicarbonate loss versus hydrogen ion load). In the present study, the following hypothesis was tested: acetazolamide-induced acidosis is associated with preretinal neovascularization in the neonatal rat. METHODS: All studies used newborn Sprague-Dawley rats raised in expanded litters of 25. Arterial blood pH was measured to determine the level of acidosis induced by intraperitoneal (IP) acetazolamide (50 or 200 mg/kg) or saline. In a separate retinopathy study, newborn rats (n = 75) were randomized to either IP acetazolamide, 50 mg/kg (low-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, retinal vasculature was assessed using ADPase staining and light microscopy. The presence and severity (clock hours) of neovascularization were assessed by three masked observers. In an additional retinopathy study, newborn rats (n = 100) were randomized to either IP acetazolamide, 200 mg/kg (high-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, the retinas were similarly analyzed. RESULTS: Neovascularization occurred in 59% of rats receiving high-dose acetazolamide (200 mg/kg). High-dose acetazolamide produced a severe acidosis (pH 7.13 +/- 0.06) during drug delivery. Low-dose acetazolamide (50 mg/kg) produced a pH (7.22 +/- 0.07) that was intermediate between high-dose (200 mg/kg) acetazolamide (P < 0.001) and saline controls (7.42 +/- 0.06, P < 0.001); however, neither low-dose acetazolamide nor saline induced preretinal neovascularization. CONCLUSIONS: Acidosis induced by high-dose acetazolamide, independent of hyperoxemia or hypoxemia, is associated with preretinal neovascularization in the neonatal rat. Induction of neovascularization appears to depend on a critical threshold of acidosis severity. This study further supports a proposed independent role for acidosis in the pathogenesis of ROP.

Acetazolamide↗