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Biomedical subjects

D He

Publications and source records attributed to D He.

At least 37 records · Page 2Linked to original sources
PubMed1998

Analysis of centrosome abnormalities and angiogenesis in epidermal-targeted p53172H mutant and p53-knockout mice after chemical carcinogenesis: evidence for a gain of function.

We previously developed a transgenic mouse model that expresses in the epidermis a murine p53172R-->H mutant (p53m) under the control of a human keratin-1-based vector (HK1.p53m). In contrast to mice with wild-type p53 and p53-knockout mice, HK1.p53m mice exhibit increased susceptibility to chemical carcinogenesis, with greatly accelerated benign papilloma formation, malignant conversion, and metastasis. In the study presented here, we examined the expression pattern of several differentiation markers and observed that p53m tumors exhibited a less differentiated phenotype than tumors elicited in non-transgenic mice. Metastasis in p53m tumors was also associated with a poorly differentiated phenotype. To determine whether genomic instability was associated with a putative gain-of-function role for this p53m, in situ examination of centrosomes was performed in HK1.p53m and equivalent p53-null papillomas. In contrast to HK1.p53m papillomas, which had centrosome abnormalities at high frequencies (75% of cells contained more than three centrosomes/cell), p53-null tumors exhibited few abnormal centrosomes (4% of cells contained more than three centrosomes/cell). To determine whether angiogenesis played a role in the rapid progression of p53m tumors, the expression of vascular endothelial growth factor, a promoter of angiogenesis, and thrombospondin-1, an inhibitor of angiogenesis, was examined in tumors derived from either p53m or p53-knockout mice. Regardless of their p53 status (wild type, p53m, p53-/-), all of the papillomas exhibited similar levels of vascular endothelial growth factor expression and decreased expression of thrombospondin-1 as did normal epidermis. In addition, tumors from different p53 genotypes showed a similar density of blood vessels. Because p53 status did not appear to play an overt role in angiogenesis, these data suggest that p53m accelerates tumorigenesis primarily by exerting a gain of function associated with genomic instability.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

CENP-G: a new centromeric protein that is associated with the alpha-1 satellite DNA subfamily.

A new constitutive centromere-specific protein (CENP) has been identified as a result of its recognition as an autoantigen by serum from a patient with gastric antral vascular ectasia disease. Conventional immunoblotting and two-dimensional double blotting with both this antiserum and a known anti-centromere antiserum showed that this antiserum predominantly recognized a Mr 95,000 protein that is different from all known CENPs. We have named this new protein CENP-G. This protein was detected at the centromeric region throughout the cell cycle. In mitosis, it was restricted to the kinetochore inner plate as shown by immunogold labeling and electron microscopy. The centromeres of some human chromosomes are known to contain two subfamilies of alpha-satellite DNA. Using immunofluorescence combined with fluorescent in situ hybridization with subfamily-specific DNA probes, we revealed that CENP-G was specifically associated with one of the subfamilies, which we have named alpha-1, but not the other. The localization and the alpha-1-specific association suggested that CENP-G may play a role in kinetochore organization and function. Like CENP-B and C, but unlike CENP-A, this protein remained with the nuclear matrix after intensive extraction. While CENP-B is absent from the human Y chromosome, the existence of CENP-G on the Y chromosome has been proven by immunofluorescence and whole chromosome painting. CENP-G was also detected in CHO, Indian muntjac and Chinese muntjac cells, suggesting that it is conserved in evolution.

Animals↗
PubMed1998

Randomized, double-blind, placebo-controlled trial of oral enalapril in patients with neurally mediated syncope.

BACKGROUND: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. METHODS AND RESULTS: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. CONCLUSIONS: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.

Administration, Oral↗
PubMed1998

Requirement for the induced expression of a cell wall associated receptor kinase for survival during the pathogen response.

Pathogen infection of angiosperms must rely on some interaction between the extracellular matrix (ECM) and the invading agent, and may be accompanied by signaling between the ECM and cytoplasm. An Arabidopsis cell wall associated receptor kinase (Wak1) has an amino-terminal domain that is tightly associated with the ECM, spans the plasma membrane and has a cytoplasmic protein kinase domain. Wak1 expression is induced when Arabidopsis plants are infected with pathogen, or when the pathogen response is stimulated either by exogenous salicylate (SA) or its analog 2,2-dichloroisonicotinic acid (INA). This Wak1 induction requires the positive regulator NPR1/NIM1. Thus Wak1 is a pathogen-related (PR) protein. Expression of an antisense and a dominant negative allele of Wak1 shows that induced expression of Wak1 is needed for a plant to survive if stimulated by INA. Ectopic expression of the entire Wak1, or the kinase domain alone, can provide resistance to otherwise lethal SA levels. These experiments suggest that Wak1 expression and other PR proteins are protecting plants from detrimental effects incurred during the pathogen response. These results provide a direct link between a protein kinase that could mediate signals from the ECM, to the events that are precipitated by a pathogen infection.

Alleles↗
PubMed1998

Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.

A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.

Aged↗
PubMed1997

Hydroxyurea can be used to increase mouse c-kit+Thy-1. 1(lo)Lin-/loSca-1(+) hematopoietic cell number and frequency in cell cycle in vivo.

The DNA synthesis inhibitor hydroxyurea (HU) was administered to determine whether it induces changes in the cell-cycle status of primitive hematopoietic stem cells (HSCs)/progenitors. Administration of HU to mice leads to bone marrow accumulation of c-kit+Thy-1.1(lo)Lin-/loSca-1(+) (KTLS) cells in S/G2/M phases of the cell cycle. HU is a relatively nontoxic, reversible cell-cycle agent that can lead to approximately a threefold expansion of KTLS cells in vivo and approximately an eightfold increase in the number of KTLS cells in S/G2/M. HSCs in HU-treated mice have undiminished multilineage long-term and short-term clonal reconstitution activity.

Animals↗
PubMed1997

Prevalence of HPV infection in esophageal squamous cell carcinoma in Chinese patients and its relationship to the p53 gene mutation.

Human papillomavirus (HPV), in particular types 16 and 18, is positively associated with anogenital cancers and may be an important etiologic factor in their pathogenesis. The goal of our study was to investigate the role of HPV infection in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and its relationship with the p53 mutation. We have examined ESCC collected from Sichuan, China, for the presence of HPV infection and p53 mutation. The presence of HPV DNA was detected by PCR-Southern analysis while the p53 mutation was analyzed by PCR-SSCP. High-risk HPV (types 16 and 18) DNA was detected in 32 out of 152 cases of ESCC examined. In contrast, HPV DNA was not detected in normal esophageal tissues excised from the distant end (tumor free) of resected ESCC. Mutation of the p53 gene was detected in 22 out of 55 cases of ESCC. The distribution of the 22 p53 mutation was: 5 in exon 5, 1 in exon 6, 5 in exon 7, 10 in exon 8 and 1 in exon 10. The p53 mutation was detected at a significantly lower rate in ESCC with HPV infection. Our results support a role of HPV infection in the pathogenesis of ESCC from a high-incidence area.

Adult↗
PubMed1997

Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells.

Our previous studies demonstrated that the promyelocytic leukemia gene, PML, encodes a growth and transformation suppressor. Overexpression of PML inhibits cancer cell growth in vitro and in vivo. In this study, we further explored the possibility of applying PML as a potential agent for developing prostate cancer gene therapy using an adenovirus delivery system. We have constructed and produced the recombinant PML-adenovirus, Ad-PML, in which the full-length PML cDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3 prostate cancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 100 multiplicity of infection (MOI), respectively. Western blotting and immunofluorescence staining demonstrated that the AD-PML-infected cells expressed a high level of PML protein. The protein expression peaked at days 3-4 postinfection, and a detectable level of PML was found at day 18 after viral infection. To test the effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOI of Ad-PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells were significantly inhibited. A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct injection of Ad-PML into DU145-induced tumors was able to repress tumor growth in nude mice by 64%. Taken together, these data indicate that PML is a tumor growth suppressor in prostate cancer and that Ad-PML may be a potential candidate for human prostate cancer therapy.

Adenoviridae↗
PubMed1997

Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas: a prospective clinico-pathological study and survival analysis of 70 patients.

The tissues from 70 Chinese patients with oesophageal squamous cell carcinoma were prospectively collected to study for the pattern of p53 mutations and its relationship with clinico-pathological features and prognosis using immunohistochemistry, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. p53 over-expression and p53 mutations were detected in 73% and 44% of the patients. These p53 aberrations had no relationship with the patient age, sex, smoking/drinking habits and tumor site, size or stage. The p53 over-expression was more intense in moderately/poorly-differentiated squamous cell carcinomas. Thirty-three p53 mutations were noted in 31 patients; 18.2% in exon 5, 15.2% in exon 6, 33.3% in exon 7 and 33.3% in exon 8. Mutations were primarily point mutations and common in codons 248, 273 and 285. There were 46% transversions, 36% transitions and 18% frameshift. The survival of the patients depended mainly on the extent of resection. In patients with stage III oesophageal cancer, the median survival of those with p53 mutations was 6.8 months whereas those without was 12.5 months. The results were of clinical importance although the value did not reach statistical significance. Thus, there was a definite role of p53 mutations in the pathogenesis of oesophageal squamous cell carcinomas. p53 mutations were not synonymous with p53 over-expression. The distribution of p53 mutations in oesophageal cancers suggested that the etiologic contribution might be complex and probably involve different exogenous and endogenous exposures. p53 mutations also appear to play a role in predicting the survival of patients with stage III oesophageal squamous cell carcinomas.

Adult↗
PubMed1997

The unexpected G0/G1 cell cycle status of mobilized hematopoietic stem cells from peripheral blood.

Treatment with a combination of cytokines and chemotherapy can effectively stimulate the release of hematopoietic stem cells (HSC) into the peripheral blood (PB), which can then be harvested for transplantation. The cell cycle status of the harvested HSC from mobilized PB (MPB) is of interest because of the impact that cell cycling may have on optimizing the conditions for ex vivo expansion, retrovirus-mediated gene transfer, and the engraftment of transplanted tissues. Therefore, we characterized the cell cycling status of mobilized HSC from mice and humans. The murine HSC, which express the phenotype c-kit+ Thy-1.1lo Lin-/lo Sca-1+, were purified from PB, bone marrow (BM), and spleen after the mice were treated with the mobilizing regimen of granulocyte colony-stimulating factor (G-CSF) or a combination of cyclophosphamide (CTX) and G-CSF. Human HSC (CD34+ Thy-1+ Lin-) and progenitor cells (CD34+ Thy-1-Lin-) were isolated from the BM of untreated healthy volunteers and from MPB of healthy volunteers and patients treated with G-CSF or a combination of CTX and GM-CSF. Cell cycle status was determined by quantitating the amount of DNA in the purified cells after staining with the dye Hoechst 33342. Fluorescence-activated cell sorting analysis of the progenitor cells from the murine and human samples showed an unexpected finding, ie, virtually none of the cells from the MPB was cycling. The G0/G1 status of HSC from MPB was surprising, because a significant proportion of HSC from BM are actively proliferating and, after mobilization, the HSC in the spleen and BM were also actively cycling.

Animals↗
PubMed1997

Presence of human papillomavirus in esophageal squamous cell carcinomas of Hong Kong Chinese and its relationship with p53 gene mutation.

There is no scientific study that has investigated the association between human papilloma virus (HPV) and p53 mutation in Hong Kong Chinese patients with esophageal cancers. The aim of this survey is to evaluate in details the prevalence and relationship of HPV and p53 mutation in these patients with esophageal squamous cell carcinomas. Fresh tissues from the resected specimens of 70 Chinese patients (59 men, 11 women) with primary esophageal squamous cell carcinomas (20 well-differentiated, 36 moderately differentiated, and 14 poorly differentiated squamous cell carcinomas) were tested for the presence of HPV and p53 mutation using the polymerase chain reaction (PCR), single-strand conformational polymorphism (SSCP) analysis, and DNA sequencing. No HPV type 18 was detected, whereas HPV type 16 was identified in 8.6% (6 of 75) of the cases. p53 mutation was found in 44% (31 of 70) of the tumors. The mean ages of HPV-positive and HPV-negative groups of patients were 55 and 64 years, respectively (P = .046, t-test). There was no correlation between the prevalence of HPV and p53 mutation in these tumors. The presence of HPV and p53 also had no relation to the sex of the patients or to the grade of the carcinomas. It is concluded that the overall low prevalence of HPV in esophageal carcinomas may suggest that the virus may not play an important role in the pathogenesis of these tumors in Hong Kong Chinese patients. Also, p53 mutation and integrated HPV DNA are not mutually exclusive in esophageal cancer.

Adult↗
PubMed1997

[The ampullar endolymhatic potential in the guinea pigs].

The purpose of this paper is to understand the physiologic feature of the ampullar endolymphatic potential (AEP) in the guinea pigs (n = 35). The high input impedence microelectrode amplifier was used. The effects of asphyxia, furosemide and ischemia on the AEP were observed. The AEP was 4.55 +/- 1.35 mV, (n = 35) in normal. The potential decreased to 2.8 +/- 0.8 mV from the original level in two minutes of asphyxia. When the respirator was turned on the AEP started to rise abruptly after a latency. In all instances there was an overshoot above the preasphyxia level. When furosemide was administered i.v. at 100 mg/kg, no effects were seen in the AEP. After obstruction of the ascending aorta to cause ischemia, the AEP continued to decline until it reached a minimum of -19.4 +/- 1.7 mV in 52.5 +/- 9.6 minutes and slowly returned to zero line in about 150 minutes. There was no obovious effect after furosemide injection. The results suggest that AEP may deffer from as the positive potential in cochlea. It is produced in the specialized cells (dark cells) of the ampullar and has special electro-physiologic characteristics.

Action Potentials↗
PubMed1997

[Effect of furosemide on the ampullar endolymphatic potential and endolymphatic Ca2+ activity].

The ampullar endolymphatic potential (AEP) and the endolymphatic Ca2+ activity were measured with double-barred Ca2+ selective microelectrodes in the experimental hydrops of guinea pigs. They showed 3.16 +/- 0.42 mV (n = 9) and (4.10 +/- 1.22) x 10(-4) M, respectively. The AEP decreased significantly at about 6 min after intravenous administration of 10 mg/kg furosemide. Its minimal value was 3.04 +/- 0.53 mV at about 40 min. But there was no significant difference between that and the value before injection. The Ca2+ activity increased significantly and reached (7.10 +/- 1.32) x 10(-4) M at about 60 min. The changes indicate that Ca2+ may play an important role in the mechanism of the furosemide test.

Animals↗
PubMed1996

Granzyme B induces apoptosis and cyclin A-associated cyclin-dependent kinase activity in all stages of the cell cycle.

Granzyme B rapidly induces apoptosis in the presence of the pore-forming protein perforin. We have examined the cell cycle restriction of this apoptosis by separating Jurkat cells into fractions representing different stages of the cell cycle by centrifugal elutriation. Cells were susceptible to apoptosis from G1 through to G2/M, with no significant resistance detected at any stage. Similarly, cells arrested at G1/S or G2/M with either hydroxyurea or nocodazole were slightly more sensitive than asynchronously growing cells. Granzyme B induces Cdc2 kinase activity and requires its induction for apoptosis. Cyclin-dependent kinase (CDK) activity is regulated by phosphorylation and association with cyclins that also control subcellular localization of the CDK/cyclin complexes. Cdc2 associates with both cyclin A, which is synthesized at G1 and S, and cyclin B, which is produced later during S and G2 before G2/M transition. We find that the CDK activity induced by granzyme B is associated primarily with cyclin A in both asynchronous and G1/S-arrested cells, while cyclin B-associated kinase activity is minimal. Because cyclin A is also able to associate with Cdk2, a kinase that is important for G1/S transition, we examined the activation of this CDK during granzyme B-induced apoptosis and find that Cdk2 is induced as rapidly as Cdc2. In conclusion, we have identified a lack of cell cycle restriction of granzyme B-induced apoptosis and the rapid activation of both cyclin A/Cdc2 and cyclin A/Cdk2 kinase activity.

Apoptosis↗
PubMed1996

Bayesian imputation of predictive values when covariate information is available and gold standard diagnosis is unavailable.

We suggest a conceptually simple Bayesian approach to inferences about the conditional probability of a specimen being infection-free given the outcome of a diagnostic test and covariate information. The approach assumes that the infection state of a specimen is not observable but uses the outcomes of a second test in conjunction with those of the first, that is, dual testing data. Dual testing procedures are often employed in clinical laboratories to assure that samples are not contaminated or to increase the likelihood of correct diagnoses. Using the CD4 count and a proxy for risk behavior as covariates, we apply the method to obtain inferences about the conditional probability of an individual being HIV-1 infection-free given the individual's covariates and a negative outcome with the standard enzyme-linked immunoad-sorbent assay/Western blotting test for HIV-1 detection. Inferences combine data from two studies where specimens were tested with the standard and with the more sensitive polymerase chain reaction test.

Algorithms↗