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Biomedical subjects

C Dong

Publications and source records attributed to C Dong.

At least 73 records · Page 4Linked to original sources
PubMed2000

Cell fate decision: T-helper 1 and 2 subsets in immune responses.

After activation CD4(+) helper T cells differentiate into T-helper (Th) 1 or Th2 effector cells. These two subsets are characterized by their distinct cytokine expression pattern and the immune function they mediate. Over the past years, a number of factors have been identified to affect helper T cell lineage determination, including antigen receptor, coreceptors and, most importantly, cytokine environment. In this review, we also summarize recent advancement in understanding of transcriptional and signaling regulation of the differentiation process. This knowledge will become important in the future to develop means in treating immune disorders.

Animals↗
PubMed2000

Characterization, chromosomal assignment, and tissue expression of a novel human gene belonging to the ARF GAP family.

We have identified and characterized a novel human ADP-ribosylation factor GTPase-activating protein (ARFGAP1) gene that is related to other members of the ARF GAP family. The full-length cDNA for human ARFGAP1 was cloned following the identification of an EST obtained by large-scale cDNA library sequencing through a Blast search of public databases. Structurally, ARFGAP1 encodes a polypeptide of 516 amino acids, which contained a typical GATA-1-type zinc finger motif (CXXCX(16)CXXC) with the four cysteine residues that are highly conserved among other members of the ARF GAP family. The conserved ARF GAP domain may emphasize the biological importance of this gene. The ARFGAP1 gene, which contained 16 exons ranging from 0.5 to 9.3 kb, was mapped to human chromosome 22q13.2-q13.3 using radiation hybridization and in silico analyses. ARFGAP1 is strongly expressed in endocrine glands and testis. Interestingly, the expression of ARFGAP1 in testis is about sixfold higher than that in ovary, indicating a possible role of ARFGAP1 in the physiological function of sperm. Expression of ARFGAP1 in four human fetal tissues and seven cancer cell lines was also detected.

ADP-Ribosylation Factors↗
PubMed2000

Familial relationships in thyroid cancer by histo-pathological type.

Thyroid cancer was studied in the Swedish Family-Cancer Database, which was updated in 1999 to cover individuals born after 1934 with their biological parents, for a total of 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included 2,435 thyroid cancers among offspring. Seventy-eight families were identified in which a parent and an offspring had a thyroid cancer. The familial standardized incidence ratios (SIRs) were 7.8 and 2.5 for male and female adenocarcinomas (papillary and follicular cancer combined), giving a sex ratio of 2. 8. The familial SIRs for medullary and anaplastic carcinomas were about 4,000 and 300, respectively, without large sex difference. Medullary thyroid cancer has been coded as a separate entity since 1985, and the high familial SIR for anaplastic cancer was probably due to medullary cancer. The familial risks for all subgroups of thyroid cancer were highest in young age groups. The familial risk of medullary thyroid cancer may be the highest ever reported in population-based studies. Multiple endocrine neoplasia type 2 (MEN2) families were probably included but unambiguous diagnosis was not possible because of the coding practice. There was a strong association of medullary thyroid cancer in offspring and endocrine gland tumors in parents, which may be related to MEN2. Adenocarcinoma in offspring was not associated with discordant parental cancer.

Adolescent↗
PubMed2000

Subsequent cancers after in situ and invasive squamous cell carcinoma of the skin.

OBJECTIVES: To compare cancer risks after in situ and invasive squamous cell carcinoma (SCC) of the skin and to determine whether these 2 forms of cancer differ in prognostic significance. PATIENTS: Subsequent events after in situ and invasive SCC were studied in the Swedish Family-Cancer Database, in which cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996. Among 22293 patients with in situ SCC, 3940 had first invasive cancer; among 17637 patients with invasive SCC, 3624 had a second occurrence of cancer. MAIN OUTCOME MEASURE: Standardized incidence ratios (SIRs), ratios of the observed to expected number of cases, served as a measure of relative risk. For overall risks, cases diagnosed within the first year of follow-up were omitted. RESULTS: The median age of onset was 72 to 73 years for in situ and invasive SCC, respectively. Standardized incidence ratios of all cancers were increased after in situ SCC (men-women, 1.5:1.3) and invasive SCC (men-women, 1.9:1.5). The subsequent occurrences of cancer and their SIRs were similar after in situ and invasive SCC, with skin cancer showing the highest SIR of 6.4:10.0. Among discordant cancers, increased SIRs were recorded for melanoma and a group of malignant neoplasms observed in patients with immunosuppression, including lymphoma and oral cancers. Subsequent cancers in the salivary glands and nasal cavity also showed increased SIRs, particularly after invasive SCC. CONCLUSION: Risks of subsequent cancers, including skin cancer, melanoma, and internal cancers, showed similar patterns in patients with in situ and invasive SCC, suggesting that the 2 groups have a similar susceptibility to cancer.

Aged↗
PubMed2000

A genetic study of Hodgkin's lymphoma: an estimate of heritability and anticipation based on the familial cancer database in Sweden.

Hodgkin's lymphoma (HL) is a heterogeneous hemopoietic malignancy. Previous studies have implicated a genetic etiology responsible for familial HL. We have estimated the heritability of HL and tested the hypothesis of genetic anticipation by using a high quality cancer database of the Swedish population. Heritability was estimated by employing a threshold-liability model. To test the hypothesis of anticipation, the usual T-test procedure was used to test whether there was a difference in cancer age-of-onset between parents and children who were affected with HL. A randomization test was carried out to test the validity of the P-values. Additional analyses were performed after stratifying the data based on birth cohorts. This data set revealed that there was a difference between the age-of-onset of parents and of offspring who were affected with HL. We also estimated the heritability of HL in the Swedish population to be approximately 28.4%. Both findings provide further evidence for a genetic basis for HL.

Adult↗
PubMed2000

Biomechanics of cell rolling: shear flow, cell-surface adhesion, and cell deformability.

The mechanics of leukocyte (white blood cell; WBC) deformation and adhesion to endothelial cells (EC) has been investigated using a novel in vitro side-view flow assay. HL-60 cell rolling adhesion to surface-immobilized P-selectin was used to model the WBC-EC adhesion process. Changes in flow shear stress, cell deformability, or substrate ligand strength resulted in significant changes in the characteristic adhesion binding time, cell-surface contact and cell rolling velocity. A 2-D model indicated that cell-substrate contact area under a high wall shear stress (20 dyn/cm2) could be nearly twice of that under a low stress (0.5 dyn/cm2) due to shear flow-induced cell deformation. An increase in contact area resulted in more energy dissipation to both adhesion bonds and viscous cytoplasm, whereas the fluid energy that inputs to a cell decreased due to a flattened cell shape. The model also predicted a plateau of WBC rolling velocity as flow shear stresses further increased. Both experimental and computational studies have described how WBC deformation influences the WBC-EC adhesion process in shear flow.

Biomechanical Phenomena↗
PubMed2000

Familial prostate cancer from the family-cancer database.

The aim of this study was to calculate the familial risk for prostate cancer (PC) for different family relationships. PC was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals born after 1934 with their biological parents, totalling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included 1035 PC cases amongst offspring. 188 families were identified where a father and a son had PC, giving a familial standardised incidence ratio (SIR) of 2.44 (2.10-2.80). The proportion of familial cancers was 18.2% amongst all PC amongst all PC amongst sons. There were only 5 pairs of affected brothers, of which 3 had an affected father. Age of onset modified familial risks modestly; the highest SIR of 4.43 (1.40-9.17) was for sons diagnosed before 50 years of age when the father was diagnosed before 65 years of age. When analysed across sites, an association of PC in one generation and stomach, liver and skin cancer and myeloma in another generation was observed. The link was most consistent for skin cancer. No maternal site was associated with a son's PC, although the SIR of breast cancer was 1.22 (0.95-1.53). No increased risk of malignancy was observed in wives of affected men excluding any shared environmental effect for PC and female cancers.

Age Distribution↗
PubMed2000

Al-Cu approximants and associated B2 chemical-twinning modes

The Al3Cu4 alloy, with an e/a ratio of 1.86 being close to ternary Al-Cu-TM (transition metal) quasicrystals, has been chosen for the search of Al-Cu approximants. Phase structures and compositions were studied using TEM, X-ray diffraction and EPMA techniques. Two new phases were found: face-centered orthorhombic oF-Al43.2Cu56.8 (a = 0.816(6), b = 1.414(9), c = 0.999(5) nm) and body-centered orthorhombic oI-Al41.3Cu58.7 (oI, a = 0.408(3), b = 0.707(4), c = 0.999(5) nm). Their e/a ratios are the same as that of the Al-Cu-Fe icosahedral quasicrystal. Both are B2 superstructures and their unit cell components can be expressed approximately as oF-Al36Cu48vacancies12 and oI-Al8Cu12vacancies4. They both exist in twinning variants of the types 120 degrees/[001] and 180 degrees/[310]. Such twinning modes indicate that these orthorhombic phases are the decomposition products of a high-temperature parent phase epsilon2-Al2Cu3, the atomic structure of which shows pentagonal atomic arrangements. Further analysis on the twinning modes of oF and oI leads to the recognition of the chemical-twinning mode of the basic B2 structure as 180 degrees/(111)B2. This kind of chemical twinning mode is responsible for the pentagonal atomic configuration in the Al-Cu approximants as well as for the pseudo-5-fold B2 twinning.

Journal Article↗
PubMed2000

Microtubule binding to Smads may regulate TGF beta activity.

Smad proteins are intracellular signaling effectors of the TGF beta superfamily. We show that endogenous Smad2, 3, and 4 bind microtubules (MTs) in several cell lines. Binding of Smads to MTs does not require TGF beta stimulation. TGF beta triggers dissociation from MTs, phosphorylation, and nuclear translocation of Smad2 and 3, with consequent activation of transcription in CCL64 cells. Destabilization of the MT network by nocodazole, colchicine, or a tubulin mutant disrupts the complex between Smads and MTs and increases TGF beta-induced Smad2 phosphorylation and transcriptional response in CCL64 cells. These data demonstrate that MTs may serve as a cytoplasmic sequestering network for Smads, controlling Smad2 association with and phosphorylation by activated TGF beta receptor I, and suggest a novel mechanism for the MT network to negatively regulate TGF beta function.

Activin Receptors, Type I↗
PubMed2000

Cancers in the first-degree relatives of children with brain tumours.

We used the nationwide Swedish Family-Cancer Database with 2060 childhood brain tumours diagnosed in the period 1958-1996 to analyse the risk of this tumour by parental cancers and in siblings of childhood brain tumour probands. Groups of patients were compared by calculating standardized incidence ratios (SIRs) for brain tumours in offspring. 1.3% of brain tumour patients had a parent with nervous system cancer; SIRs were 2.4 and 1.88 for diagnostic ages < 5 and < 15 years, respectively. The data showed distinct patterns of familial risks for childhood brain tumours, the SIR was 10.26 for brain astrocytoma given a parent with meningioma. Parental colon cancer was associated with offspring ependymoma (SIR 3.70), and parental salivary gland cancers with offspring medulloblastoma (SIR 13.33, but two cases only). SIR for sibling nervous system cancer from childhood brain tumour probands was 3.55 up to age 61.

Adolescent↗
PubMed2000

Familial relationships in squamous cell carcinoma of the skin.

The Swedish Family-Cancer Database, which was updated in 1999 to cover individuals born after 1934 with their biological parents, totals 9.6 million persons. We used this resource to study invasive and in situ skin cancers. We identified 198 families in which a parent and an offspring had skin cancer. The familial standardized incidence ratios (SIRs) were 2.4 for invasive and 2.8 for in situ skin cancers in offspring. The SIRs for offspring depended only weakly on the age at diagnosis, as evaluated in two age groups. Compared with offspring whose parents had a single skin cancer, offspring whose parents had multiple skin cancers had a 70% increase in SIR. The discordant parental cancer sites that showed associations with skin cancer in offspring were melanoma, ocular melanoma, and a group of cancers observed in immunosuppressed patients.

Adolescent↗
PubMed2000

Cancer in husbands of cervical cancer patients.

We used the Swedish Family-Cancer Database to analyze the spectrum of cancers diagnosed in husbands of women with in situ or invasive cervical cancer, and we compared these to second carcinogenic events in women presenting with these cancers. Our hypothesis was increased cancer susceptibility from human papilloma virus (HPV). When the wives had in situ or invasive cervical cancer, the standard incidence ratios (SIRs) for anal cancer in husbands were 1.75 (95% CI = 1.05-2.62) and 1.92 (95% CI = 0.69-3.76). Anal cancer was also increased as a second primary cancer in women. Other common cancers were related to tobacco smoking. The results indicate that HPV infection is associated with anal cancer in both men and women.

Adult↗
PubMed2000

Second primary cancer after in situ and invasive cervical cancer.

The Swedish Family-Cancer Database was used to analyze 9,426 second primary cancers in 117,830 subjects diagnosed with in situ and 17,556 subjects with invasive cervical cancer from the years 1958-1996. We calculated standardized incidence ratios (SIRs) from age- and period-specific rates for all women. SIRs were elevated after both in situ and invasive cervical cancer for cancers of the upper aerodigestive tract, anus, pancreas, lung, other female genitals, and urinary bladder. Anus and other female genitals, known targets of human papilloma virus, showed SIRs exceeding 3.0 and 10 or more within the year of diagnosis of cervical cancer, probably implying the effects of diagnostic intensity or transient faltering of host immunosurveillance. Among the remaining sites, smoking appeared to be the major cause, but for urinary bladder cancer it only explained one-half of the excess; human papilloma virus infection, possibly through immunosuppression, could account for the remaining excess. Although urinary bladder cancer showed a relatively small SIR compared with anal cancer, because it is more common, the number of attributable cases was about equal for the two sites. Invasive cervical cancer showed an SIR of 2.3 after in situ cancer. On follow-up, we also observed increased SIRs at many radiosensitive sites 10 or more years after diagnosis of invasive cervical cancer.

Adult↗
PubMed2000

Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands.

The study aimed at probing the possible role of human papillomavirus (HPV) infection in squamous cell carcinomas of the upper aerodigestive tract, with a special reference to tonsillar cancer. We used the Swedish Family Cancer Database to analyse second cancers in the upper aerodigestive tract of women first diagnosed with in-situ or invasive cervical cancer. First cancers of their husbands were also analysed. Standardized incidence ratios (SIRs) were calculated for female and male cancers, adjusted for age at diagnosis, period, sex, socio-economic status and residential area. Among women, increases were observed at many sites, but tonsillar cancers were increased only among women aged 50 years or more at diagnosis of in-situ cervical cancer (SIR 2.58). The increases at these sites are probably ascribed to the effects HPV, smoking, alcohol or their interaction. Husbands of cervical cancer patients developed an excess (SIR over 2.00) of both tonsillar cancer (SIR 2.39 when wife with in-situ cancer and SIR 2.72 when wife with invasive cervical cancer) and cancer of the tongue. The excess of tonsillar cancer among husbands of women with HPV-associated neoplastic lesions of the cervix supports the a priori hypothesis that HPV may be involved in tonsillar carcinogenesis.

Adult↗
PubMed2000

Evaluation of hepatitis C virus glycoprotein E2 for vaccine design: an endoplasmic reticulum-retained recombinant protein is superior to secreted recombinant protein and DNA-based vaccine candidates.

Hepatitis C virus (HCV) is the leading causative agent of blood-borne chronic hepatitis and is the target of intensive vaccine research. The virus genome encodes a number of structural and nonstructural antigens which could be used in a subunit vaccine. The HCV envelope glycoprotein E2 has recently been shown to bind CD81 on human cells and therefore is a prime candidate for inclusion in any such vaccine. The experiments presented here assessed the optimal form of HCV E2 antigen from the perspective of antibody generation. The quality of recombinant E2 protein was evaluated by both the capacity to bind its putative receptor CD81 on human cells and the ability to elicit antibodies that inhibited this binding (NOB antibodies). We show that truncated E2 proteins expressed in mammalian cells bind with high efficiency to human cells and elicit NOB antibodies in guinea pigs only when purified from the core-glycosylated intracellular fraction, whereas the complex-glycosylated secreted fraction does not bind and elicits no NOB antibodies. We also show that carbohydrate moieties are not necessary for E2 binding to human cells and that only the monomeric nonaggregated fraction can bind to CD81. Moreover, comparing recombinant intracellular E2 protein to several E2-encoding DNA vaccines in mice, we found that protein immunization is superior to DNA in both the quantity and quality of the antibody response elicited. Together, our data suggest that to elicit antibodies aimed at blocking HCV binding to CD81 on human cells, the antigen of choice is a mammalian cell-expressed, monomeric E2 protein purified from the intracellular fraction.

Animals↗
PubMed2000

c-Jun NH(2)-terminal kinase inhibits targeting of the protein phosphatase calcineurin to NFATc1.

The protein phosphatase calcineurin is a critical mediator of calcium signals during T-cell activation. One substrate of calcineurin is the transcription factor NFATc1, which is retained in the cytoplasm of quiescent cells. NFATc1 activation requires the translocation of the transcription factor into the nucleus, a process that is mediated by calcineurin. This interaction with calcineurin requires a targeting domain (PxIxIT motif) located in the NH(2)-terminal region of NFATc1. Here we demonstrate that the calcineurin targeting domain of NFATc1 is phosphorylated and inactivated by the c-Jun NH(2)-terminal kinase (JNK). This disruption of calcineurin targeting inhibits the nuclear accumulation and transcription activity of NFATc1 and accounts for the observation that Jnk1(-/-) T cells exhibit greatly increased NFATc1-dependent nuclear responses.

Amino Acid Motifs↗