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Biomedical subjects

T Zheng

Publications and source records attributed to T Zheng.

At least 127 records · Page 7Linked to original sources
PubMed1997

Cytokine- and virus-stimulated airway smooth muscle cells produce IL-11 and other IL-6-type cytokines.

Inflammation and smooth muscle abnormalities coexist in human airway disorders, and inflammation modulates the proliferative and contractile properties of airway smooth muscle cells. To determine whether human airway smooth muscle (HASM) cells have the ability to regulate local inflammatory processes, we characterized the interleukin (IL)-6-type cytokine production of HASM cells in vitro. We demonstrated that HASM cells are potent producers of IL-11 when stimulated with IL-1 or transforming growth factor-beta 1 (TGF-beta 1) and that IL-11 levels are synergistically increased by IL-1 and TGF-beta 1 in combination. These studies also demonstrated that IL-1 and TGF-beta 1-stimulated HASM cells produce IL-6 and leukemia inhibitory factor but not oncostatin M and that respiratory syncytial virus and parainfluenza virus type 3 stimulate HASM cell IL-11 production. Finally, they demonstrate that, in all cases, the stimulation of HASM cell IL-11 elaboration is pretranslationally mediated since cytokine- and virus-induced alterations in IL-11 protein production were associated with proportionate changes in IL-11 mRNA accumulation. HASM cells are potent producers of IL-11 and other IL-6-type cytokines and may be important regulators of local airway inflammation.

Animals↗
PubMed1997

[Study of estrogen receptors in hepatocellular carcinoma and its response to anti-estrogen therapy].

OBJECTIVE: To study the usefulness of anti-estrogen therapy for moderately and advanced hepatocellular carcinoma (HCC). METHODS: Estrogen receptors (ER) were examined in 51 cases of HCC by immunohistochemical staining of needle aspiration biopsy HCC specimens. The cases studied were randomly divided into two groups: the control group (N = 25) and the anti-estrogen treated group (N = 26). Patients in the control group were given matelin and immune RNA while those in the anti-estrogen treated group were given Tamoxifen in addition. A 50% reduction of serum AFP level and a 50% decrease in tumor size were considered therapeutically effective. RESULTS: In the control group, the response rate as judged by AFP level (RR-AFP) and by tumor size (RR-TS) in the ER+ patients was 42.9% (3 of 7 cases) and 14.3% (1 of 7 cases), respectively, while the 2 RRs in the ER- patients were lower but the difference was statistically insignificant. In contrast, in the Tamoxifen-treated group, RR-AFP was 83.3% (5 of 6 cases) and RR-TS was 50.0% (3 of 6 cases). The difference in RRs of ER+ patients in the 2 groups was statistically significant. No complete remission was observed. CONCLUSION: Endocrinotherapy may be of value in the treatment of ER+ HCC.

Adult↗
PubMed1997

Mitochondrial tRNA(Leu(UUR)) gene mutation diabetes mellitus in Chinese.

OBJECTIVE: To ascertain the prevalence and clinical features of mitochondrial tRNALeu(UUR) gene nucleotide (nt) 3243 A-->G mutation diabetes mellitus in Chinese and to establish the approaches for genetic diagnosis of this subtype of diabetes during routine daily clinical practice. METHODS: Mitochondrial nt 3243 A-->G mutation was screened among 207 unrelated non-insulin-dependent diabetes mellitus (NIDDM) patients by using polymerase chain reaction (PCR)/Apa I restriction endonuclease digestion. Samples with positive result were confirmed by DNA sequence analysis. Genetic and clinical analysis were carried out in family members of the proband with positive genetic diagnosis. RESULTS: Positive results were found in two subjects during screening of unrelated NIDDM patients, which account for 2.4%-11.1% of NIDDM subjects with uncommon clinical features (with early age-of-onset, with low body-mass-index and on insulin therapy) or with positive family history of diabetes consistent with or unable to exclude from maternal inheritance. Genetic diagnosis was positive in 10 out of 25 family members in the pedigrees of these two probands. CONCLUSIONS: Mitochondrial tRNALeu(UUR) gene nt 3242 A-->G mutation should be considered in diabetic patients with the above-mentioned clinical features. The genetic diagnosis in daily clinical practice can be performed with allele specific priming amplification, or PCR/Hae III or Apa I digestion which are technically simple to perform and diagnostically easy to define.

Adolescent↗
PubMed1997

Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein.

AIDS-associated Kaposi's sarcoma (AIDS-KS), the most common malignant complication of human immunodeficiency virus infection, is characterized by neoplastic proliferation of mesenchymal cells. AIDS-KS cells release and respond to an array of cytokines through specific plasma membrane receptors. Specific targeting of potent cytotoxic agents to cell surface receptors/antigens on Kaposi's sarcoma cells may provide effective therapy for this malignancy. We have identified a new target in the form of an interleukin 13 (IL-13) receptor that is overexpressed in the five AIDS-KS cell lines examined. Radiolabeled IL-13 cross-linked to a single protein of about Mr 70,000 in AIDS-KS cells. We utilized a chimeric cytotoxic protein composed of IL-13 and a truncated Pseudomonas exotoxin (IL13-PE38QQR), which was found to be specifically and highly cytotoxic to AIDS-KS cells, as determined by protein synthesis inhibition and clonogenic assays. IL13-PE38QQR demonstrated significant antitumor activity in a human epidermoid carcinoma xenograft model. Normal human umbilical vein-derived endothelial, lymphoid, and bone marrow precursor cells expressed low levels of IL-13 receptors, and IL-13 toxin was not cytotoxic to them. Thus, IL-13 receptor on AIDS-KS cells may represent a novel plasma membrane protein(s) that could be utilized to target therapeutic agents.

ADP Ribose Transferases↗
PubMed1996

Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.

Airway Obstruction↗
PubMed1996

The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators.

The cloning and expression of two new human cDNAs encoding proteins highly related to the far upstream element-binding protein (FBP) are described. FBP, FBP2, and FBP3 comprise a family of single-strand DNA- binding proteins that possess all of the general features of more conventional transcription factors. The FBPs each bind sequence specifically to only one strand of the far upstream element (FUSE; originally identified upstream of c-myc), and each possesses potent activation domains when fused to the GAL4 DNA-binding domain and assayed by transient transfection. Typical of transcription factors, the proteins are most highly related in their central, DNA-binding domains, but extensive homology is also shared within the tyrosine-rich, carboxyl-terminal activation domains. Comparison with GenBank sequences revealed a fourth FBP family member encoded by Caenorhabditis elegans chromosome III, illustrating the high degree of homology in this evolutionarily ancient and conserved family.

Amino Acid Sequence↗
PubMed1996

The effects of preparations of human chorionic gonadotropin on AIDS-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma is the most common cancer in patients with the acquired immunodeficiency syndrome (AIDS). Recently, certain preparations of human chorionic gonadotropin (hCG) have been shown to inhibit the growth of Kaposi's sarcoma cell lines in vitro and in immunodeficient mice. METHODS: After in vitro evaluation of four commercially available hCG preparations, the most active product was evaluated in 36 patients with AIDS-related Kaposi's sarcoma. In a phase 1-2 trial, 24 patients received intralesional injections of hCG three times a week for two weeks at doses of 250, 500, 1000, or 2000 IU (6 patients each). In each patient three nodular lesions were injected, two with the drug and one with diluent alone. In a double-blind trial, 12 additional patients were randomly assigned to receive intralesional injections of 2000 IU of hCG or diluent alone (6 patients each; two lesions per patient). At the conclusion of therapy, the lesions were measured, their gross appearance assessed, and biopsy specimens evaluated. RESULTS: A.P.L. (Wyeth-Ayerst), which had the most in vitro activity against Kaposi's sarcoma cell lines, was selected for the clinical investigation. Treatment with A.P.L. was well tolerated at all doses. In the cohorts given 250, 500, 1000, and 2000 IU, 1, 5, 5, and 10 of the 12 injected lesions responded, respectively (P=0.03 for trend). Complete tumor regression was observed in one lesion each at the 250-IU and 500-IU doses, in two lesions given the 1000-IU dose, and in five lesions given the 2000-IU dose. In the double-blind study, none of the 12 lesions in the six patients injected with diluent had responses, as compared with 10 of the 12 lesions in the six patients injected with hCG (P=0.015). Microscopical evidence of apoptosis was observed only in hCG-treated lesions. The percentage of cells that died increased in a dose-dependent manner (P<0.001). Serum levels of follicle-stimulating hormone (P=0.002) and luteinizing hormone (P=0.001) declined after the last injection of hCG, but there was no effect on these hormones in the diluent-treated patients. CONCLUSIONS: The intralesional injection of hCG induces the regression of AIDS-related Kaposi's sarcoma lesions in a dose-dependent manner. The response of these tumors appears to be mediated by the induction of apoptosis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Time trend and age-period-cohort effect on incidence of bladder cancer in Connecticut, 1935-1992.

Earlier studies indicated that the incidence rates for bladder cancers rose rapidly in both the United States and Europe. Tobacco smoking is considered to be the major risk factor for urinary bladder cancer, and recent studies from Connecticut show that several smoking-related cancers have started leveling off or decreasing. The time trend for bladder cancer, however, is not clear in Connecticut. The current study examined the long-term trend of bladder cancer in Connecticut. Our results show that urinary bladder cancer has been increasing, with a marked increase among males. The rate of increase, however, has slowed since the early 1980s. Birth-cohort examination shows that the rates have leveled off for those born after about 1935 in both males and females. Age-period-cohort modeling results also show that the birth-cohort patterns of bladder cancer are somewhat similar to those observed for lung cancer in Connecticut, thus supporting the findings from analytical epidemiologic studies which indicate that cigarette smoking is one of the major risk factors for urinary bladder cancer. Our results also suggest that the difference in environmental and occupational exposures between males and females may be responsible for the large difference in the incidence rate of bladder cancer seen between the sexes.

Adult↗
PubMed1996

Malignant melanoma risk factors by anatomic site: a case-control study and polychotomous logistic regression analysis.

This population-based case-control study systematically examined reported malignant melanoma risk factors by anatomic site. Study subjects consisted of 548 invasive melanoma cases diagnosed in Connecticut during 1987-1989 and 494 randomly selected controls. Multivariate polychotomous logistic regression was used to determine whether risk factors differed across anatomic sites. Risk factors examined included demographic and pigmentary characteristics, sun exposure-related factors, anatomic site-specific sunburn, recreational water activity clothing habits and number of nevi. A pattern of site-specificity was observed for sunburn. A history of sunburn at an anatomic site was specifically related to the development of malignant melanoma at that site more so than at other sites. This site-specificity was consistent with a direct role for intense, intermittent sun exposure in the development of melanoma. Age and gender were the only risk factors that differed significantly in effect across anatomic sites. The age difference was explained by differences in histologic subtype across sites. The gender difference could not be explained by sex differences in anatomic site-specific sunburns or in recreational water activity clothing habits. Alternative explanations include sex differences in behavioral patterns of sun exposure that we did not measure and as yet unelucidated differences in susceptibility to melanoma according to sex and anatomic site.

Adult↗
PubMed1996

Time trend and age-period-cohort effect on incidence of thyroid cancer in Connecticut, 1935-1992.

Recent studies from Europe suggest a continuing increase in thyroid cancer, but it is unclear whether this trend also applies to the United States. The current study examined the long-term trend of thyroid cancer in Connecticut. Our results show that the overall age-adjusted incidence rate of thyroid cancer has been increasing in Connecticut, from 1.30/100,000 in 1935-1939 to 5.78/100,000 in 1990-1992 in females, and from 0.30/100,000 in 1935-1939 to 2.77/100,000 in 1990-1992 in males. The increase mainly comes from papillary carcinoma of the thyroid. The birth cohort analyses indicate that the increase in thyroid cancer occurred among cohorts born between 1915 and 1945, which experienced an increase of 31.4% every 5 years in males and 17.3% in females over the period 1960-1979. For those born since the 1945 cohort, the incidence has been decreasing, at rates of 9.3% and 8.3% every 5 years over the period 1975-1992 in males and females, respectively. Age-period-cohort modeling results also suggest a strong birth cohort effect on the observed time trend in both sexes, which closely follows the introduction of radiation treatment of benign childhood conditions in the head and neck between 1920 and the 1950s in the United States. Our results are consistent with the suggested radiation hypothesis, indicating that radiation treatment of benign childhood conditions in the head and neck is largely responsible for the observed increase of thyroid cancer in Connecticut.

Adenocarcinoma, Follicular↗
PubMed1996

Eosinophil-fibroblast interactions. Granule major basic protein interacts with IL-1 and transforming growth factor-beta in the stimulation of lung fibroblast IL-6-type cytokine production.

To test the hypothesis that eosinophil major basic protein (MBP) is an important regulator of fibroblast effector function, we characterized the effects of MBP on human lung fibroblast production of the IL-6-type cytokines, IL-6, IL-11, and leukemia inhibitory factor. Unstimulated fibroblasts did not produce substantial quantities of these cytokines, while IL-1 and TGF-beta(1) stimulated these cytokines in a potent fashion. MBP at doses < or = 44 micrograms/ml did not stimulate IL-6-type cytokine production. It did, however, interact in a synergistic, dose- and time-dependent fashion with rIL-1-alpha and TGF-beta(1) to further increase IL-6-type cytokine elaboration. These MBP-induced increases in cytokine production were associated with proportionate alterations in mRNA accumulation. In contrast, eosinophil-derived neurotoxin did not regulate fibroblast cytokine production, and MBP did not augment fibroblast granulocyte-macrophage-CSF, or type I collagen production, or fibroblast proliferation in this culture system. The effects of MBP could not be attributed to cell cytotoxicity or contaminants in the MBP preparations. They were, however, at least partially charge mediated, since heparin abolished the effects of MBP on IL-1-stimulated cells, and the surrogate cationic molecule poly-L-arginine mimicked the stimulatory effects of MBP on fibroblast IL-6-type cytokine elaboration. These studies demonstrate that MBP interacts in a synergistic fashion with rIL-1-alpha or TGF-beta(1) to further augment fibroblast IL-6-type cytokine production. They also demonstrate that this stimulation is pretranslationally mediated and due, in part, to the cationic nature of the MBP molecule. MBP regulation of fibroblast cytokine production may play an important role in the pathogenesis of eosinophilic disorders of the airway or other organs.

Blood Proteins↗
PubMed1996

A model for the effect of cigarette smoking on lung cancer incidence in Connecticut.

Population based data on smoking history derived from NCHS surveys were used to develop a model for lung cancer incidence in Connecticut. Trends in smoking prevalence suggest that, while the prevalence in men increased earlier than women, more male smokers have quit than their female counterparts. These trends in smoking prevalence suggest striking gender differences in a period effect for the smoking prevalence. Estimates of the proportion of current smokers, ex-smokers, and the mean duration of smoking were used in a model for the lung cancer incidence rates. The form for the relationship between smoking history and the incidence rate for these subgroups was based on information from cohort studies. The models represented a mixture of the smoking subgroups where the effect of smoking was considered to be either a multiplicative effect on the underlying age distribution, or a separate effect in which the level of exposure was the sole contribution to risk among smokers. The multiplicative model explained more than 80 per cent of the deviance for the period and cohort effects, while the non-multiplicative model could only account for trends in females. Hence, these results suggest that a sizeable portion of the period and cohort contributions to the lung cancer incidence trends in Connecticut can be attributed to the multiplicative model that utilizes this smoking information, although the lack of more detailed information is a limiting factor in developing the model.

Adult↗
PubMed1996

Continuing increase in incidence of germ-cell testis cancer in young adults: experience from Connecticut, USA, 1935-1992.

The current study is designed to examine long-term trends by histologic types of testis cancer in Connecticut. A regression model was used to identify age, period, or cohort as determinants of the time-trend on histologic types of testis cancer. The results from this descriptive epidemiologic study show that the overall age-adjusted incidence rate of testis cancer has increased 3.5-fold in Connecticut during the past nearly 60 years of cancer registration. The rates for seminoma and non-seminoma have been increasing since the mid-1950s and increase in a similar manner for those aged 15 to 49. The largest increase was observed in the age groups 20 to 44 for seminoma and 15 to 34 for non-seminoma. The observed increase was limited to whites. The results from age-period-cohort modeling suggest that the observed increase in seminoma before 1950s could be largely attributable to a period effect, while the increase for cohorts born after about 1910 both for seminoma and for non-seminoma are mainly explained by a strong birth-cohort effect. Therefore, the observed increase in germ-cell testis cancer in this population is likely to continue in the coming years. Thus far, the proposed hypotheses, such as exposure to DES in utero, earlier lifetime exposure to viruses, trauma or unusual amounts of heat to the testis, cannot adequately explain the observed incidence patterns of testis cancer. Analytical epidemiologic studies with large sample size are urgently needed to examine the risk factors responsible for the increase.

Adolescent↗
PubMed1996

The continuing increase in adenocarcinoma of the uterine cervix: a birth cohort phenomenon.

BACKGROUND: Adenocarcinoma of the uterine cervix has been reported to be increasing among young white women and earlier studies suggest a birth cohort pattern for the observed increase. No study, however, has examined the time trends of adenocarcinoma of the cervix by birth cohort. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) data through 1990, the current study is designed to examine the time trends of invasive adenocarcinoma by birth cohort. An age-period-cohort model was fitted to the annual-age-specific rates to identify the components of birth cohort and time period as determinants of the observed time trends. RESULTS: The results from this study clearly show that invasive adenocarcinoma of the uterine cervix has been increasing in both whites and blacks, but the increase is statistically significant only among whites, reaching 4.2 percent per year for those born since 1935. The results also show that the recent increase in invasive adenocarcinoma started among those born around the mid 1920s, and a strong birth cohort effect is largely responsible for the observed increase. CONCLUSION: Invasive adenocarcinoma of the uterine cervix is increasing among recent birth cohorts. Analytical epidemiological studies are urgently needed to explore the risk factors responsible for the increase. The time trends for adenocarcinoma of the cervix should also be carefully monitored in the coming years.

Adenocarcinoma↗
PubMed1996

[Commodity identification of semen Plantaginis and herba Plantaginis].

The Semen Plantaginis from 29 provinces and regions and the Herba Plantaginis from 18 provinces and regions in our country were identified, and the main commodities of these two crude drugs are described in this paper. The identification may serve as a scientific basis for expanding new drug resources.

Drug Contamination↗