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Biomedical subjects

J Zhou

Publications and source records attributed to J Zhou.

At least 145 records · Page 8Linked to original sources
PubMed2001

Dynamic renal scintigraphy in diagnosis of upper urinary tract obstruction in transplanted kidney.

Nuclide renal dynamic imaging was performed on 88 (110 times) transplanted kidney. Two kinds of renal scintigraphic characteristics were identified in recipients with supravesical obstruction of the graft. First, the regular type was characterized by radioactivity defect area in kidney parenchyma during early uptake period followed by ureteropelvic retention. Second, the tubular type was typified by cortical retention and attenuation in collecting system during the whole test period with a special sign of "hollow kidney". Non-obstructive dilated calyces showed similar signs as the regular type. Acute rejection reaction and tubule necrosis demonstrated obstructive time-activity curves. However, the radioactivity retention appeared in cortex. It was suggested that dilated calyces and obstructive renogram might not be reliable evidence for upper urinary tract obstruction. The signs of radioactivity attenuation in kidney parenchyma during early uptake period followed by ureteropelvic retention may be more valuable for the evaluation. As for tubular obstruction, specified "hollow kidney" was the characteristic sign which is helpful for the diagnosis.

Adolescent↗
PubMed2001

The exogenous wild-type p14ARF gene induces growth arrest and promotes radiosensitivity in human lung cancer cell lines.

The cyclin-dependent kinase inhibitor p16INK4a encoded by the INK4A/CDKN2A/MTS1 gene is a frequent target of 9p21 inactivation in human lung cancers. The p14ARF transcript, which is an alternative spliced form of this locus, is also altered or deleted in a proportion of human lung cancers and has been shown to inhibit cell cycle progression as an endogenous cellular regulator of the p53 protein, raising the possibility that it might constitute an additional lung tumor suppressor gene at the 9p21 locus. To test the candidacy of p14ARF as a lung cancer suppressor and assess the role it plays in radiosensitivity, we transfected the wild-type p14ARF gene into four cell lines which had various endogenous gene backgrounds of INK4A-/p53+/RB+ (A549 and H460), INK4A+/p53+/RB- (H446) as well as p14ARF+/p53-/RB+ (Calu-1). We found that transfection of p14ARF is related to an obvious growth inhibition in all wtp53 cell lines, regardless of INK4A/ARF and RB status. Although it has been shown that p53-induced G1 checkpoint in response to DNA damage by ionizing radiation is p14ARF-independent, we found the radiosensitivity of two p14ARF-deficient cell lines was increased after p14ARF gene transfer. The results indicated that cell cycle redistribution after acquiring the exogenous gene might be the main explanation for the enhanced sensitization. An increased radiation-induced apoptotic proportion in one cell line also suggested a fortified p53 function that might be triggered by the restored p14ARF protein.

Cell Cycle↗
PubMed2001

The potential of plasma thrombomodulin as a biomarker of portal vein tumor thrombus in hepatocellular carcinoma.

PURPOSE: To study the relationship between thrombomodulin (TM) plasma levels and the formation of portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma (HCC). METHODS: Pre- and-postoperative plasma TM levels of 45 patients with HCC and six patients with benign liver-occupying lesion were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of TM in human HCC tissues was determined by immunohistochemistry assay. RESULTS: The preoperative plasma TM level of patients with HCC (10.2+/-5.7 ng/ml) was significantly higher than that of those patients with benign liver-occupying lesion (6.1+/-2.2 ng/ml) and that of normal controls (5.7+/-1.0 ng/ml), respectively (P<0.05). The postoperative TM level of 40 patients with HCC whose tumors had been removed decreased significantly than the preoperative TM level (10.8+/-5.3 ng/ml versus 7.6+/-4.2 ng/ ml, P < 0.05), whereas there was no significant difference between the preoperative and postoperative TM level of six patients with benign liver-occupying lesion (6.1+/-2.2 ng/ml versus 5.9+/-1.8 ng/ml, P>0.05). The preoperative plasma TM level of patients with single HCC (11.5+/-5.9 ng/ml) or no PVTT (11.4+/-5.6 ng/ml) was significantly higher than that of those patients with multiple HCC (8.1+/-4.6 ng/ml) or PVTT (6.9+/-4.5 ng/ ml), respectively (P<0.05). The preoperative plasma TM level of the patients with HCC tissue that stained positive for TM was significantly higher than those with tissue that stained negative for TM (12.2+/-6.5 ng/ ml versus 8.7+/-4.6 ng/ml, P<0.05). The postoperative plasma TM level showed no difference between the patients with HCC tissue stained positive and negative for TM (8.3+/-4.1 ng/ml versus 7.6+/-4.4 ng/ml, P>0.05). There was also no significant difference between the plasma TM level and other clinicopathological futures. CONCLUSIONS: Plasma TM increases in patients with HCC and can be a biomarker of the formation of PVTT.

Adult↗
PubMed2001

Homocysteine and atherothrombosis.

Atherosclerosis with or without thrombosis superimposed is the most frequent cause of ischemic heart disease (IHD), peripheral arterial disease, and a main cause of stroke. Conflicting results have been reported in genetic, observational, and experimental studies on the relationship between homocysteine and these atherothrombotic diseases. Although cardiovascular complications are common in homocystinuric patients (severe hyperhomocysteinemia), IHD, the most frequent manifestation of atherothrombosis in the general population, appears to be rare. On the basis of findings in individuals with hyperhomocysteinemia of genetic origin, there is in fact no clear evidence for a causal role of homocysteine in the pathogenesis of atherothrombotic disease, and the positive association between plasma homocysteine and IHD observed in many, but not all epidemiologic studies does not prove causality. To infer causality from observational studies, there should be a temporal, consistent, strong, independent, graded (dose-response effect), and duration-dependent relationship between exposure and outcomes, and a biologically plausible mechanism should exist. The relationship between plasma homocysteine levels and IHD does not fulfill these criteria beyond reasonable doubt. In the general population, plasma homocysteine levels are to a great extent determined by dietary habits, and plasma homocysteine could be a marker, or a consequence, of atherothrombosis and/or risk-associated behavior (e.g., a diet low in fruits and vegetables) rather than a cause of atherothrombosis. Experimentally, hyperhomocysteinemia is not in itself atherogenic in normal animals with relatively low plasma cholesterol levels. The homocysteine theory of atherosclerosis should be tested more thoroughly in hypercholesterolemic animals that develop atherosclerosis spontaneously to determine whether elevated plasma homocysteine levels are harmful under atherogenic conditions. A causal role of homocysteine in atherothrombotic disease remains to be established.

Arteriosclerosis↗
PubMed2001

Freunds adjuvant alone is antiatherogenic in apoE-deficient mice and specific immunization against TNFalpha confers no additional benefit.

TNFalpha participates in the pathogenesis of atherosclerosis. The effect of immunization against TNFalpha on development of advanced vascular lesions in atherosclerosis-susceptible apoE-deficient mice was investigated. At 5-7 weeks of age, animals received immunization with either Freunds adjuvant and a recombinant antigenic TNFalpha molecule (TNF106), Freunds adjuvant alone, or no immunization. All mice received a Western-type high-fat diet for 12 weeks. Aortic sinus lesion area was determined by microscopic morphometry, the total aortic arch cholesterol content was determined by gas chromatography, and antibodies against TNFalpha, malondialdehyde-modified low density lipoprotein, or heat shock protein 60, were assessed by ELISAs. Immunization with TNF106 induced high-titered circulating antibodies against TNFalpha (n=23), and these antibodies were not detected in mice immunized with Freunds adjuvant alone (n=22), or in non-immunized control animals (n=25). After 12 weeks, the atherosclerotic lesion size was significantly reduced in immunized animals, whether they had been immunized with TNF106 or Freunds adjuvant alone, and the total lesional cholesterol content was decreased in mice immunized with TNF106. There were no correlations between circulating antibody titers and plaque size, total aortic arch cholesterol content, or plasma lipid levels, respectively. Administration of Freunds adjuvant alone can thus reduce formation of mature atherosclerotic lesions in apoE-deficient mice and this response is not modified by specific immunization against TNFalpha.

Animals↗
PubMed2001

Overexpression of agouti protein and stress responsiveness in mice.

Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the beta-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light-dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors.

Adrenocorticotropic Hormone↗
PubMed2001

Expression of early lung cancer detection marker: hnRNP-A2/B1 and its relation to microsatellite alteration in non-small cell lung cancer.

We have reported that a mouse monoclonal antibody, 703D4, which recognizes heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) can frequently detect lung cancer in exfoliated sputum epithelial cells 1-2 years earlier than routine chest X-ray or sputum cytomorphology. We along with others have shown that microsatellite alteration (MA) at selected loci can be recognized in sputum cells prior to clinical lung cancer. The present study was undertaken to determine how frequently the expression of hnRNP-A2/B1 message is associated with neoplastic clonal expansion as shown by MA in 41 cases of non-small cell lung cancer (NSCLC). We used Northern blotting to evaluate hnRNP-A2/B1 mRNA expression in lung tumor and remote noninvolved lung. We evaluated microsatellite instability (i.e. shifts; MI) or loss of heterozygosity (LOH) with a panel of 13 microsatellite markers at loci identified previously as susceptible in NSCLC. Of the 41 tumors, 25 (61%) over-expressed hnRNP-A2/B1 and 33 (80%) demonstrated MA in at least one of 13 loci (58% in at least two loci). The association between MA (one locus) and the overexpression of hnRNP-A2/B1 is statistically significant (P=0.0082), and those lung tumors with MA at two or more loci were significantly more likely to over-express hnRNP-A2/B1 mRNA (P=0.004). MA of loci on 3p were the only MA statistically associated with hnRNP-A2/B1 message overexpression (P=0.001). We conclude that lung tumor cells undergoing clonal expansion frequently upregulate hnRNP-A2/B1.

Adult↗
PubMed2001

In vitro metabolism studies of the prodrug, 2',3',5'-triacetyl-6-azauridine, utilizing an automated analytical system.

The purpose was to study in vitro metabolism of 2',3',5'-triacetyl-6-azauridine (1) by porcine liver esterase (PLE) and in human plasma using an automated analytical system developed previously. A gradient-LC method was developed to study the concentration-time course of 1 and its metabolites. A fast-LC assay was used to study the temperature effect on the metabolism of 1 by the PLE. 1 and all of its proposed possible metabolites were separated by the gradient-LC method in less than 10 min. Two simplified kinetic schemes were developed to describe the time course of 1, the intermediates and final metabolites with only five rate constants for the metabolisms of 1 by PLE and four rate constants in human plasma. Both enthalpy and entropy of activation in the in vitro metabolism of 1 by PLE were obtained.

Algorithms↗
PubMed2001

Role of aromatase in endometrial disease.

Aromatase is the key enzyme for estrogen biosynthesis. It is normally expressed in the human ovary, skin, adipose tissue and brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of post-menopausal endometriosis using an aromatase inhibitor.

Aromatase↗
PubMed2001

PARM: a practical utility for drug design.

To accommodate situations in which the 3D structure of the target receptor is not available, we have developed the Pseudo Atomic Receptor Model (PARM) software package. In this article we describe PARM and illustrate its use with three examples: elemenes (potential anticancer drugs), angiotensin converting enzyme inhibitors, and human HIV-1 inhibitors TTD (1,1,3-trioxo-2H, 4H-thieno[3,4-e][1,2,4] thiadiazine derivatives). The results show that PARM can build models with favorable cross-validation statistics (Rcv2 values 0.7-0.9) and give helpful SAR insight. PARM has certain advantages: (a) it can be used for many systems, regardless of whether the 3D structure of the receptor is known; (b) PARM models were demonstrated to be highly statistically reliable; and (c) PARM analyses are robust and reproducible.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic breast cancer.

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical stages of lung development and carcinogenesis. To determine if the expression of hnRNP-A2/B1 is an informative biomarker in breast carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in archived specimens. Expression was detected in 48/85 (56.5%) primary invasive breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1 expression compared to normal or transformed breast cells. Expression of hnRNP-A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately with decreased cell growth. These results warrant further evaluation of hnRNP-A2/B1 as a marker of breast carcinogenesis.

Biomarkers, Tumor↗
PubMed2001

Signal transduction targets in androgen-independent prostate cancer.

Prostate cancer (PCa) first manifests as an androgen-dependent disease. Thus, androgen-deprivation therapy is a standard regimen for patients with metastatic PCa. Despite the initial success of androgen-deprivation therapy, PCa inevitably progresses from being androgen dependent (AD) to androgen independent (AI), and this marks the poor prognosis of this disease. Relapse of AIPCa becomes life threatening and accounts for the majority of mortality of PCa patients. Currently, no effective therapy is available for controlling AIPCa. Therefore, the challenge in providing a new intervention is to understand the fundamental changes that occur in AIPCa. Increasing evidence indicates that, under androgen-deprived milieu, several signal networks elicited by peptide growth factors dictate the AI phenotype of PCa. This review covers the latest studies investigating the potential involvement of autocrine growth factors in cell proliferation, survival, metastasis, and the reciprocal interaction with the androgen receptor pathway. In addition, loss of the negative feedback mechanism of the signal cascade further amplifies the effect of growth factors, and thus contributes significantly to the onset of AIPCa. The understanding of the signal target(s) in AIPCa should provide the new markers for prognosis and a new strategy for prevention and therapy.

Adenocarcinoma↗
PubMed2001

When openness to experience and conscientiousness are related to creative behavior: an interactional approach.

This study adopted an interactional approach to understanding how 2 of the Five-Factor traits, openness to experience and conscientiousness, are related to creative behavior in the workplace. Openness to experience is theorized to result in high levels of creative behavior and conscientiousness is theorized to result in low levels of creative behavior when the situation allows for the manifestation of the trait influences. More specifically, the authors hypothesized that openness to experience would result in high levels of creative behavior if feedback valence were positive and job holders were presented with a heuristic task that allowed them to be creative. The authors also hypothesized that conscientiousness would result in low levels of creative behavior if supervisors engaged in close monitoring and coworkers were unsupportive. The authors tested their hypotheses in a sample of office workers, and 5 out of the 6 hypotheses were supported.

Adult↗
PubMed2001

An in vivo reporter system for measuring increased inclusion of exon 7 in SMN2 mRNA: potential therapy of SMA.

Spinal muscular atrophy (SMA) is a degenerative motor neuron disorder resulting from homozygous loss of the SMN1 gene. SMN2, a nearly identical copy gene, is preserved in SMA patients. A single nucleotide difference between SMN1 and SMN2 causes exon 7 skipping in the majority of SMN2 mRNA. Gene therapy through modulation of SMN2 gene transcription in SMA patients may be possible. We constructed a series of SMN mini-genes comprised of SMN exon 6 to exon 8 sequences fused to green fluorescence protein (GFP) or luciferase reporters, to monitor SMN exon 7 splicing. These reporters recapitulated the splicing patterns of the endogenous SMN gene in stable cell lines. The SMN1-luciferase reporter was approximately 3.5-fold more active than SMN2-luciferase and SMN1-GFP intensities were visually distinguishable from SMN2-GFP. We have screened chemical inducers and inhibitors of kinase pathways using stable SMN-reporter lines and found that the phosphatase inhibitor sodium vanadate specifically stimulated exon 7 inclusion within SMN2 mRNAs. This is the first compound identified that can stimulate exon 7 inclusion into transcripts derived from the endogenous SMN2 gene. These results demonstrate that this system can be utilized to identify small molecules that regulate the splicing of SMN exon 7.

Artificial Gene Fusion↗