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Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 397 records · Page 22Linked to original sources

Time trends and familial risks in squamous cell carcinoma of the skin.

OBJECTIVES: To study time trends and familial clustering of invasive and in situ squamous cell skin cancers (SCC), with particular reference to sun-exposed and covered sites of the body. DESIGN: Epidemiologic follow-up study of the whole population. SETTING: The Swedish Family-Cancer Database from the year 2000, to cover individuals born after 1931 with their biological parents, totaling 10.2 million persons. PATIENTS: Cancer data were obtained from the Swedish Cancer Registry from 1961 through 1998 and included 1907 invasive SCCs in offspring and 12,702 and 7167 in fathers and mothers, respectively. The numbers of patients affected by in situ SCC were 2666, 13,739, and 13,321, respectively. MAIN OUTCOME MEASURES: Standardized incidence ratios and 95% confidence intervals were calculated for SCC in offspring when parents had SCC. Incidence rates were calculated for the population in the Database. RESULTS: Incidence trends showed a large increase in reported cases of SCC and particularly of in situ SCC. Among invasive cases, the increase was largest among covered sites. A clear cohort effect was observed particularly for SCC on covered sites. Familial standardized incidence ratios for offspring combining invasive and in situ SCC were 2.25 (95% confidence interval, 1.93-2.59) for concordant exposed sites and 2.60 (95% confidence interval, 1.38-4.20) for concordant covered sites, suggesting no difference between the body parts within the present statistical power. CONCLUSIONS: The higher increase in incidence on covered sites and the strong cohort effect suggest a contribution by intentional tanning. The observed equal increase in the familial effect on exposed and covered sites suggests that familial risk increases proportionately to the background rate.

Adolescent↗

Administration of antisense oligodeoxyribonucleotides targeting NF-kappaB prolongs allograft survival via suppression of cytotoxicity.

Presentation of alloantigens by antigen-presenting cells (APC) deficient in expression of costimulatory molecules (CM) induces alloantigen-specific hyporesponsiveness or tolerance. NF-kappaB has been shown to be a crucial transcription factor that regulates CM expression on the surface of APC. We designed an antisense phosphorothioate oligodeoxynucleotide (ODN) to specifically inhibit mRNA of mouse NF-kappaB, resulting in a deficiency in CM expression on APC that may prolong organ allograft survival. Anti-NF-kappaB ODN was delivered systemically by an osmotic pump implanted in the abdominal cavity of recipients following transplantation of vascularized heart allografts. The animals in control groups were given scrambled control ODN or were left untreated. Normal C3H (H2(k)) recipients rejected B10 (H2(b)) heart allografts at a median survival time (MST) of 15 days. A 14-day administration of 12.5 mg/kg/day anti-NF-kappaB ODN prolonged the survival of cardiac allografts to an MST of 25 days (P <0.05). In contrast, a scrambled control ODN was not effective (MST 17 days, P >0.05 compared to untreated controls). To investigate the underlying mechanisms of the immunosuppressive effect of anti-NF-kappaB ODN administration, graft infiltrating cells, spleen cells, and serum were collected from animals on day 7 posttransplant. Freshly isolated graft-infiltrating cells from anti-NF-kappaB ODN-treated recipients exhibited significantly decreased donor-specific CTL activity. Generation of CTL activity of spleen T cells from anti-NF-kappaB ODN-treated recipients was also impaired compared with untreated animals. Administration of anti-NF-kappaB ODN did not influence the titers of complement-dependent cytotoxic antibodies. These data suggest that treatment with anti-NF-kappaB ODN markedly inhibits the cellular response of allograft recipients, resulting in significant prolongation of allograft survival. Antisense ODN therapy targeting NF-kappacB may be a novel strategy for future immunosuppressive therapy.

Animals↗

Establishment and evaluation of bone mineral density reference databases appropriate for diagnosis and evaluation of osteoporosis in Chinese women.

This study was designed to establish Bone Mineral Density (BMD) Reference Databases for multiple skeletal sites appropriate for the diagnosis and evaluation of osteoporosis (OP) in Chinese women. We recruited 2702 healthy Chinese women, 5-96 years of age, for BMD assessment. BMD values at multiple skeletal sites including anteroposterior (AP) and lateral (Lat) lumbar spine, hip, and forearm were measured by dual-energy X-ray absorptiometry (DXA) using a QDR 4500A device; results were analyzed according to age group using eight regression models. BMD Reference Databases (CWD) were established according to the best regression equation and compared with Hologic reference databases for "Oriental Women" (OWD). Results indicated that the cubic regression model was superior to the quadratic, linear, logarithmic, and exponential regression models, etc. for our purpose, with a determinate coefficient ( R(2)) of 0.363-0.650 ( P = 0.000). We included 1636 female patients, aged 35-86 years, in our tests. In comparison with Hologic Reference Databases, the mean detection rate of OP in the newly established BMD Reference Databases for Chinese Women (CWD) was 16.0% +/- 2.68% lower (range, 13.7%-20.5%) at the AP spine, 16.8% +/- 11.0% lower (range, 3.5%-32.8%) at the Lat spine (except for L4), 18.7% +/- 4.6% lower (range, 12.6%-24.2%) at the hip, and 14.3% +/- 6.9% higher (range, 4.7%-24.3%) at the forearm. The difference in detection rates for OP was significant between the two reference databases ( P = 0.000), which was consistent with the differences in peak BMD values and the biological variability between them. Based upon our data, we confirmed that the Hologic BMD Reference Databases for Oriental Women (OWD) were not suitable for the diagnosis of OP in Chinese women; the BMD Reference Databases for Chinese Women (CWD) established in this study would provide reliable diagnostic standards for detection of OP in the women of South China.

Adolescent↗

Large-scale molecular and tissue microarray analysis of mesothelin expression in common human carcinomas.

The 40-kilodalton processed glycoprotein, mesothelin, is highly expressed in epithelial mesotheliomas and adenocarcinomas of the ovary (serous papillary) and pancreas, but its expression in a large series of other common carcinomas has not been completely explored. In the present study, we used oligonucleotide and tissue microarrays to profile the expression of the mesothelin gene (MSLN) and encoded protein, respectively. Among 150 carcinomas of multiple anatomic sites, we found the highest average expression of MSLN in serous carcinomas of the ovary and adenocarcinomas of the pancreas, consistent with previous reports, as well as measurable but less-striking expression in pulmonary, gastric/esophageal, and colorectal adenocarcinomas. On tissue microarrays containing 621 carcinomas derived from the same and additional sites as those profiled by gene expression, mesothelin immunoreactivity was highest in cancers of the ovary (serous papillary, endometrioid, and undifferentiated) and pancreas, with less frequent staining seen in adenocarcinomas of the endometrium, lung, and stomach/esophagus. Some immunopositivity was observed in 42% of pulmonary adenocarcinomas, including 18% that had >50% of tumor cells that were immunoreactive. Some 14% of breast and 30% of colorectal adenocarcinomas showed immunopositivity, but no case contained >50% tumor cells that were immunoreactive. Mesothelin was either entirely absent or present in <5% of carcinomas of the prostate, bladder/ureter, liver, kidney, and thyroid. Overall, we observed good concordance between the results obtained by oligonucleotide and tissue microarrays. This large study of the MSLN gene and protein expression in common carcinomas provides data for future investigations that evaluate the utility of mesothelin/megakaryocyte potentiating factor as a potential serum tumor marker or target of immunotoxin-based therapy in human cancers.

Biomarkers, Tumor↗

Codon 201 polymorphism of DCC gene is a prognostic factor in patients with colorectal cancer.

The polymorphism at codon 201 of the "deleted in colorectal carcinoma" (DCC) gene has been liked to susceptibility to colorectal cancer. However, its clinicopathological significance has not been reported. We examined the codon 201 polymorphism and loss of heterozygosity (LOH) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 59 colorectal cancers, 48 samples from transitional mucosa and 67 samples from normal mucosa. The frequencies of the polymorphism did not significantly differ from normal to transitional mucosa and to tumor, but LOH was increased from transitional mucosa to tumor. Almost all of the LOH cases showed the polymorphism. The polymorphism was increased from well/moderately to poorly differentiated and to mucinous carcinoma (P=0.03). The polymorphism was more frequently seen in advanced stages than in earlier stages (P=0.02), and further predicted worse survival (P=0.04). The data suggest that the codon 201 polymorphism of the DCC gene was a target of LOH, and predicted prognosis in colorectal cancer patients.

Aged↗

Detection of lung cancer with positron coincidence gamma camera using fluorodeoxyglucose in comparison with dedicated PET.

OBJECTIVE: Dual-head gamma cameras with sodium iodide (NaI) detectors operated in coincidence mode provide a new approach for imaging with positron-labeled tracers. The purpose of this study was to evaluate the feasibility of FDG imaging with positron coincidence detection gamma camera (PCD) in detecting lung tumor in comparison with FDG imaging with the dedicated positron emission tomography (PET). METHODS AND MATERIAL: Twenty-six lesions of 13 patients with suspected lung cancer were studied with both FDG PET and FDG PCD on the same day. Pulmonary lesions were analyzed visually and semi-quantitatively using the ratio of target-to-background counts (T/B ratio). RESULTS AND CONCLUSIONS: FDG PCD and FDG PET could detect visually 21 lesions (80.8%) and 23 lesions (88.0%), respectively. The mean T/B ratio and standard deviation (S.D.) of FDG PCD was 4.6 +/- 3.9, significantly lower than that of FDG PET (11.4 +/- 6.6, P<0.001). When pulmonary lesions were no more than 2.0 cm in diameter, the sensitivity of FDG PCD was 37.5%, significantly inferior to that of FDG PET (62.5%, P<0.001). There was no statistically significant difference of the sensitivity between the FDG PCD and FDG PET in lesions of more than 2.0 cm in diameter. FDG PCD with uniform attenuation correction was clinically available in detecting lung cancer. However, the sensitivity for small lesions less than 2.0 cm was limited. The application of measured attenuation correction and scatter correction may to be needed to improve the detectability of FDG PCD, especially for detecting small lung cancer.

Adult↗

Sex hormones and their receptors in patients with age-related cataract.

PURPOSE: To determine the sex hormone levels in the serum and aqueous humor in patients with age-related cataract and the corresponding hormone receptors in cataract lens epithelial cells (LECs). SETTING: Research Laboratory, International Intraocular Implant Training Center, Tianjin Medical University, Tianjin, China. METHODS: Serum and aqueous humor were drawn from patients with cataract and a control group. Enzyme-linked immunosorbent assay was used to determine the levels of estradiol, progesterone, and testosterone in the serum and the aqueous. The anterior lens capsules with attached LECs were obtained during cataract surgery, and the expressions of estrogen receptor, progesterone receptor, or androgen receptor were examined by immunohistochemistry. RESULTS: The testosterone level in the serum was significantly higher in the control group than in the cataract group. In the cataract group, there was no difference between sexes in the serum levels of estradiol or progesterone; however, the testosterone level in men was significantly higher than in women. The aqueous level of each hormone was lower than in serum; however, there was no difference between sexes and no association with corresponding serum levels. No estrogen, progesterone, or androgen receptor was detected in the LECs of patients with age-related cataract. CONCLUSIONS: There was no statistical difference between men and women or between the cataract and control groups in the levels of estradiol or progesterone in serum. There was no between-sex difference in the aqueous levels. It appears that sex hormone levels can be regarded only as a risk factor for cataractogenesis, not as a key factor.

Aged↗

Crystal structure of human riboflavin kinase reveals a beta barrel fold and a novel active site arch.

Riboflavin kinase (RFK) is an essential enzyme catalyzing the phosphorylation of riboflavin (vitamin B(2)) to form FMN, an obligatory step in vitamin B(2) utilization and flavin cofactor synthesis. The structure of human RFK revealed a six-stranded antiparallel beta barrel core structurally similar to the riboflavin synthase/ferredoxin reductase FAD binding domain fold. The binding site of an intrinsically bound MgADP defines a novel nucleotide binding motif that encompasses a loop, a 3(10) helix, and a reverse turn followed by a short beta strand. This active site loop forms an arch with ATP and riboflavin binding at the opposite side and the phosphoryl transfer appears to occur through the hole underneath the arch. The invariant residues Asn36 and Glu86 are implicated in the catalysis.

Adenosine Diphosphate↗

Cytoplasmic polyhedrosis virus structure at 8 A by electron cryomicroscopy: structural basis of capsid stability and mRNA processing regulation.

The single-shelled cytoplasmic polyhedrosis virus (CPV) is a unique member of the Reoviridae. Despite lacking protective outer shells, it exhibits striking capsid stability and is capable of endogenous RNA transcription and processing. The 8 A three-dimensional structure of CPV by electron cryomicroscopy reveals secondary structure elements present in the capsid proteins CSP, LPP, and TP, which have alpha+beta folds. The extensive nonequivalent interactions between CSP and LPP, the unique CSP protrusion domain, and the perfect inter-CSP surface complementarities may account for the enhanced capsid stability. The slanted disposition of TP functional domains and the stacking of channel constrictions suggest an iris diaphragm-like mechanism for opening/closing capsid pores and turret channels in regulating the highly coordinated steps of mRNA transcription, processing, and release.

Animals↗

Role for plastin in host defense distinguishes integrin signaling from cell adhesion and spreading.

Integrin ligation activates both cell adhesion and signal transduction, in part through reorganization of the actin cytoskeleton. Plastins (also known as fimbrins) are actin-crosslinking proteins of the cortical cytoskeleton present in all cells and conserved from yeast to mammals. Here we show that plastin-deficient polymorphonuclear neutrophils (PMN) are deficient in killing the bacterial pathogen Staphylococcus aureus in vivo and in vitro, despite normal phagocytosis. Like integrin beta2-deficient PMN, plastin-deficient PMN cannot generate an adhesion-dependent respiratory burst, because of markedly diminished integrin-dependent syk activation. Unlike beta2(-/-) PMN, plastin-deficient PMN adhere and spread normally. Deficiency of plastin thus separates the classical integrin receptor functions of adhesion and spreading from intracellular signal transduction.

Animals↗

Global regulation of Hox gene expression in C. elegans by a SAM domain protein.

Polycomb group (PcG)-mediated repression of C. elegans Hox genes has not been demonstrated, and genes homologous to components of one of the PcG complexes (PRC1) have not been identified in the C. elegans genome. We find that a mechanism of general Hox gene repression exists in C. elegans, carried out in part by SOP-2, a protein related to, but not orthologous with, any PcG protein. sop-2 mutations lead to widespread ectopic expression of Hox genes and homeotic transformations. SOP-2 contains a SAM domain, a self-associating protein domain found in other repressors, including a core component of PRC1 and ETS transcription factors. Phylogenetic analysis indicates that this domain is more closely related to those of the ETS family than to those of PcG proteins. The results suggest that global repression of Hox genes has been taken over by a different branch of the SAM domain family during the evolution of nematodes.

Amino Acid Sequence↗

Disruption of Id1 reveals major differences in angiogenesis between transplanted and autochthonous tumors.

Id genes regulate tumor angiogenesis and loss of Id1 inhibits tumor xenograft growth in mice. Here we evaluate the role of Id1 in a more clinically relevant tumor model system using a two-step chemical carcinogenesis protocol. Remarkably, we find that Id1-/- mice are more susceptible to skin tumorigenesis compared to their wild-type counterparts. Cutaneous neoplasms in Id1-/- mice show increased proliferation without alterations in tumor angiogenesis; however, Id1-/- mice possess 50% fewer cutaneous gammadelta T cells than their wild-type counterparts due to an intrinsic migration defect associated with loss of expression of the chemokine receptor, CXCR4. We suggest that there are important differences between the mechanisms of angiogenesis in transplanted and autochthonous tumors and that these findings will have significant implications for the potential utility of antiangiogenic therapies in cancer.

Animals↗

A real-time and dynamic biological information retrieval and analysis system (BIRAS).

The aim of this study is to design a biological information retrieval and analysis system (BIRAS) based on the Internet. Using the specific network protocol, BIRAS system could send and receive information from the Entrez search and retrieval system maintained by National Center for Biotechnology Information (NCBI) in USA. The literatures, nucleotide sequence, protein sequences, and other resources according to the user-defined term could then be retrieved and sent to the user by pop up message or by E-mail informing automatically using BIRAS system. All the information retrieving and analyzing processes are done in real-time. As a robust system for intelligently and dynamically retrieving and analyzing on the user-defined information, it is believed that BIRAS would be extensively used to retrieve specific information from large amount of biological databases in now days. The program is available on request from the corresponding author.

Animals↗

Screening for functional genes related to a novel gene, AngRem104, in human mesangial cells by cDNA microarray.

AngRem104 is a novel gene recently identified in human mesangial cells induced by angiotensin II. cDNA microarray was performed to screen the functional genes related to AngRem104. Thirty-one genes were up-regulated while 2 genes were down-regulated. Of all the up-regulated genes, fibronectin, one of the major extracellular matrixes, was up-regulated with over-expression of AngRem104.

Fibronectins↗

Nuclear transport by laser-induced pressure transients.

PURPOSE: Control of the transport of molecules into the nucleus represents a key regulatory mechanism for differentiation, transformation, and signal transduction. Permeabilization of the nuclear envelope by physical methods can have applications in gene therapy. Laser-induced pressure transients can produce temporary aqueous pores analogous to those produced by electroporation and that the cells can survive this procedure. In this study, we examine the role of the pressure transients in creating similar pores in the nuclear envelope. METHODS: The target human peripheral blood mononuclear cells in a 62 microM 72 kDa fluoresceinated dextran solution were exposed to the pressure transients generated by laser ablation. An in vitro fluorescence confocal microscope was used to visualize and quantify the fluoresceinated dextran in the cytoplasmic and nuclear compartments. RESULTS: In contrast to electroporation, the pressure transients could deliver 72 kDa fluoresceinated dextrans, which are normally excluded by the nucleus, across the nuclear envelope into the nucleus. In addition to creating pores in the plasma membrane, temporary pores were also created in the nuclear envelope following exposure to pressure transients. CONCLUSION: The production of temporary nuclear pores could provide a unique resource for drug-delivery and gene therapy.

Cell Nucleus↗

The impact of tobacco on lung health in China.

China has the largest production and consumption of tobacco worldwide. It has witnessed a dramatic increase in tobacco consumption over the past two decades, with more than 34.8 million cartons of cigarettes being produced and 34.7 million sold annually. Approximately 67% of males and 4% of females aged over 15 years in China are smokers, and the total of over 320 million Chinese smokers represents about one-third of all smokers worldwide. The continuous, rapid increase in the number of Chinese smokers is largely due to teenagers taking up smoking. Among teenagers aged 15-19 years, 18% of men and 0.28% of women (making a total of 9 million teenagers) are smokers. The prevalence of passive smoking is very high at 53.5%, about 0.3 billion people aged above 15 years were affected. The average daily consumption of tobacco per person in China rose from one cigarette in 1952 to 10 cigarettes in 1990, a rate similar to that of the USA 40 years earlier. It seems inevitable that China will witness a substantial increase in mortality following this increase in smoking. Based on current smoking rates, the predicted deaths attributed to smoking in China will rise to 3 million in 2050. If the current smoking pattern in China remains unchanged, 100 million men now under 30 years will die from smoking-related diseases. The respiratory system is harmed most by tobacco smoke. Over two-thirds of all deaths related to smoking in China are attributed to chronic obstructive pulmonary disease (COPD), lung cancer and pulmonary tuberculosis. The morbidity of COPD alone in China is estimated at over 3%, or 25 million people, of whom 72% were smokers. The Chinese government consistently supports smoking control and advocates smoking abstinence via laws to restrain the sale and advertising of tobacco. These actions have been successful in some aspects, and in particular, more people are aware that 'cigarette smoking is harmful to health'. In future, the emphasis of smoking control should be directed at restraining teenagers and adolescents from smoking. Cigarette smoking has already caused significant ill-health to the Chinese population with over 1 million people dying each year of various disorders caused by smoking. However, the peak of smoking-induced diseases is still to come and therefore, it is very important to strengthen anti-smoking measures so as to have a far-reaching effect on the future health of the Chinese population.

Adolescent↗

Familial and attributable risks in cutaneous melanoma: effects of proband and age.

We studied familial risks in invasive and in situ cutaneous melanoma by comparing the occurrence of melanoma, or discordant cancer, between parents and offspring, and between siblings, based on the Swedish Family Cancer Database of over 10 million individuals. Offspring were 0-66 y of age. Cancers were obtained from the Swedish Cancer Registry from 1961 to 1998. The study was based on 24,818 invasive and 5510 in situ cases of melanoma. Standardized incidence ratios were calculated for familial risk. The standardized incidence ratios for offspring was 2.40 (95% confidence intervals: 2.10-2.72) when only the parent had melanoma and it was 2.98 (95% confidence intervals: 2.54-3.47) when only a sibling was affected; when both a parent and a sibling were affected the standardized incidence ratios was 8.92 (95% confidence intervals: 4.25-15.31). The respective population attributable risks were 1.38, 1.20, and 0.10%. The familial risk showed a clear age dependence and somewhat higher risk in in situ melanoma than in the invasive counterpart. The highest standardized incidence ratio of 61.78 (5.82-227.19) was noted for offspring whose parent had multiple melanomas. Superficially spreading melanoma showed the highest familial risk both among invasive and in situ tumors. Melanoma associated with breast, nervous system, and skin cancers, and in situ melanoma possibly also with connective tissue and thyroid tumors and multiple myeloma.

Age Distribution↗