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Biomedical subjects

T Zheng

Publications and source records attributed to T Zheng.

At least 145 records · Page 8Linked to original sources
PubMed1996

Glucokinase gene variants in Chinese subjects with the common form of NIDDM.

OBJECTIVE: To determine whether mutation of the coding or junction region of glucokinase gene (GCK) is also the pathogenic cause of the common form of non-insulin-dependent diabetes mellitus (NIDDM) in Chinese. METHODS: Single strand conformation polymorphism (SSCP) analysis was performed after the 12 exons and junction regions of GCK of each subject studied were separately amplified with polymerase chain reaction (PCR). The molecular scanning was carried out in 30 Chinese subjects with common form NIDDM having the age of onset at or before 45 years, and/or with positive family history of diabetes mellitus (NIDDM-A group). Further screening of the mutation/variation found was conducted in 56 NIDDM subjects (NIDDM-B group) and 134 non-diabetes subjects (ND group) in order to define their frequencies. RESULTS: No mutation was found by molecular scanning in coding or junction region of GCK in NIDDM-A group. A variant of intron I b was detected in GCK of NIDDM subjects, especially in those with early age of onset and/or with positive family history of diabetes. Significant difference in incidences was found between ND group and NIDDM-A+B group (0% vs 4.7%, Fisher exact P = 0.022). CONCLUSIONS: (1) Mutation of coding and junction regions of GCK is not the main pathogenic factor of common form NIDDM in Chinese subjects. (2) A variant of GCK intron I b may be found in NIDDM in Chinese, especially in those with early age of onset and/or with positive family history of diabetes. Its role in the expression of GCK remain to be elucidated.

Adult↗
PubMed1996

Prevention of disability and rehabilitation--results from a collaborative project in China.

Eight different geographical districts in China varying in urban and rural characteristics from 6 provinces and 2 municipalities were selected as pilot areas of the project. The interventions included early detection and treatment of neuritis, self-care training, adapted footwear, surgery, comprehensive treatment of complicated ulcers, and prostheses. Main changes in eye, hand and foot impairments between baseline assessment and assessment at 2 years have been presented in this paper.

China↗
PubMed1995

Time trend in pancreatic cancer incidence in Connecticut, 1935-1990.

A total of 13,246 incident pancreatic cancer cases, reported to the Connecticut Tumor Registry between 1935 and 1990, were included in our study. Results indicate that the overall age-adjusted incidence rate of pancreatic cancer increased between 1935 and 1964 in males, and leveled off thereafter. Since 1975, the incidence rate has in fact been decreasing, from 12.04/100,000 in 1975-79 to 10.44/100,000 in 1985-90. In females, the overall age-adjusted incidence rate also increased between 1935 and 1974. Since then, however, it has remained relatively stable. Age-specific incidence rates also show no signs of an increase in rate from any age group, or from either sex for recent birth cohorts. There is also no clear increase in the incidence of pancreatic cancer in any of the ethnic/gender categories since the early 1970s. Age-period-cohort modeling shows that the increasing birth cohort trend peaked among those born around 1920-1925 and, for recent birth cohort, a slightly decreasing trend was observed in both males and females. Our study reveals no signs of an increase in the immediate future in pancreatic cancer incidence rate in any of the sex, ethnic and age groups in Connecticut.

Adult↗
PubMed1995

Alcohol, tobacco, diet and the risk of oral cancer: a pooled analysis of three case-control studies.

This combined analysis of data from three large case-control studies of oral cancer confirms the important effect of tobacco in the aetiology of the disease. The studies have been conducted in the United States, Italy and China and results for risks associated with tobacco smoking were generally consistent across centres, while those for alcohol were not; increased risks amongst alcohol drinkers were evident in two centres but not in the study conducted in Turin, Italy. In addition, the combined analysis had large enough numbers to analyse the risk of tobacco consumption in non-drinkers. In females these showed increased risks while in males the effect of tobacco alone was weaker. Given the popularity of tobacco smoking, and its consequent high attributable risk in terms of oral cancer it is reassuring, in terms of public health, that cessation will result in a substantial reduction in risk; a 30% reduction in risk for those stopping smoking between 1 and 9 years, and a 50% reduction for those stopping more than 9 years. Although encouraging smokers to stop should be the principal aim, decreases in risk for everyone could be achieved by encouraging high fruit and vegetable consumption.

Adult↗
PubMed1995

Prevention of impairment in leprosy; results from a collaborative project in China.

OBJECTIVE: to evaluate programs of prevention and treatment of impairments due to leprosy in 8 geographical areas in the People's Republic of China. DESIGN: follow up of cohorts of leprosy patients receiving a range of different interventions. SETTING: 8 different geographical areas in China, varying in urban and rural characteristics from 6 provinces and 2 municipalities. SUBJECTS: leprosy patients who were receiving or had completed a course of antileprosy chemotherapy. INTERVENTIONS: a range of interventions, including steroids, self-care training, adapted footwear, surgery and provision of prostheses. MAIN OUTCOME MEASURES: changes in eye, hand and foot impairments between baseline assessment and assessment at 2 years. RESULTS: 232 out of 3571 patients assessed monthly over 2 years developed acute neuritis and, in most areas, were promptly and adequately treated. Regular self care of eyes was established in 238 out of 313 patients with lagophthalmos and was associated with reduction in the prevalence of conjunctivitis. Regular self care of hands was established in 730 out of 1010 patients with neurological impairment of the hand; this was associated with a reduction (80%) in hand cracks and wounds. Regular self care of feet was established in 745 out of 1094 patients with neurological impairment of the feet; this was associated with a 83% reduction in patients with cracks and a 33% reduction in patients with sole wounds. A footwear program was established in all 8 areas providing footwear to 4698 patients over the 2-year period; this was associated with a reduction of 61% and 21% in patients with cracks and wounds, respectively. Management of complicated sole wounds in 256 patients resulted in 69% of these patients being free of sole wounds at 2 years. Targets for reconstructive surgery and amputations were not fully attained, but lower limb prostheses were provided for 306 patients. CONCLUSIONS: leprosy is a chronic disease characterized by peripheral neuropathies which can result in increasing secondary impairments and disabilities. The emphasis, in countries such as China where the chemotherapy programs have been effectively implemented, is shifting to prevention and treatment of impairments. This innovative program in China has successfully demonstrated that it is possible to prevent and reverse impairments due to leprosy.

Artificial Limbs↗
PubMed1994

Histamine augments cytokine-stimulated IL-11 production by human lung fibroblasts.

Histamine mediates its effects via histamine receptors and by participating in a multicellular cytokine cascade. IL-11 is a stromal cell-derived cytokine with biologic activities that overlap with IL-6. To further understand the biology of histamine and IL-11, we determined whether histamine regulates the production of IL-11 by human lung fibroblasts. Histamine was a weak stimulator of IL-11 production. Importantly, it also interacted in a synergistic fashion with TGF-beta 1 to further augment IL-11 protein production and mRNA accumulation. This synergistic interaction was not altered by the H2 receptor antagonist cimetidine and could not be reproduced with the H2 receptor agonist 4-methylhistamine. In addition, it was not abrogated by the cyclic nucleotide-dependent protein kinase inhibitor N-(2-1-guanidinoethyl)-5 isoquinolinesulfonamide hydrochloride), and histamine and TGF-beta 1 did not stimulate intracellular cAMP. In contrast, the synergy was abrogated by the H1 histamine receptor antagonists diphenhydramine and pyrilamine, could be reproduced when histamine was replaced with the H1 agonist 2-methylhistamine, and was abrogated by the calmodulin antagonists N-(6-aminohexyl)-1-napthalenesulfonamide), N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide), and trifluoperazine dichloride and by the intracellular calcium chelator 1,2-bis-(2-amino-5-bromo-phenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester. In addition, although TGF-beta 1 did not alter cytosolic Ca2+, histamine caused a biphasic increase in cytosolic Ca2+, and the majority of cells incubated with TGF-beta 1 plus histamine exhibited sustained Ca2+ oscillations. These studies demonstrate that histamine is an important regulator of fibroblast IL-11 production, that histamine interacts with TGF-beta 1 in the induction of this cytokine, and that this interaction is mediated, to a great extent, by a pretranslational mechanism that is dependent on H1 receptors and a calcium/calmodulin-dependent activation pathway.

Calcium↗
PubMed1994

Epithelial interleukin-11. Regulation by cytokines, respiratory syncytial virus, and retinoic acid.

Interleukin-11 (IL-11) is a pleiotropic cytokine with effects that overlap with IL-6. To determine if IL-11 is produced by epithelial cells, we determined whether human alveolar A549 cells and airway 9HTE cells produce IL-11. We also determined whether retinoic acid (RA) altered this IL-11 production. Unstimulated cells produced low levels of IL-11, while IL-1, transforming growth factor (TGF-beta 1), and respiratory syncytial virus (RSV) stimulated IL-11 protein production and mRNA accumulation in a time- and dose-dependent fashion. IL-1 and TGF-beta 1 also interacted in a synergistic, and presumedly transcriptional, fashion since they augmented A549 cell IL-11 protein production and mRNA accumulation without altering IL-11 mRNA half-life. In contrast, IL-4 only weakly stimulated, and IL-7, hepatocyte growth factor, and herpes simplex virus Type 2 did not stimulate, IL-11 production. RA did not alter the IL-11 production of unstimulated or RSV infected cells. It did, however, inhibit rIL-1-stimulated and synergistically augment TGF-beta-stimulated IL-11 production. Thus, IL-1, TGF-beta, and RSV stimulate epithelial-like cell IL-11 production, and RA regulates these inductive processes in a stimulus-specific fashion.

Cells, Cultured↗
PubMed1994

Time trend and the age-period-cohort effect on the incidence of histologic types of lung cancer in Connecticut, 1960-1989.

BACKGROUND: Recent epidemiologic studies have suggested changing patterns of lung cancer incidence by histologic type. The observed time trends have been attributed to a change in the rate of cigarette smoking, changes in exposure to new environmental carcinogens, and changes in the criteria for the histopathologic diagnosis of lung cancer. The current study was designed to examine the incidence patterns of lung cancer by histologic type in Connecticut and to use this information to project the future trend of the disease in this population. METHODS: This study was based on all the lung cancer cases reported to the Connecticut Tumor Registry between 1960 and 1989. On the basis of this data set, crude and age-adjusted incidence rates of lung cancer were calculated by histologic type for each sex. The age-specific incidence rates are presented by calendar year and cohort year of birth. A regression model was used to identify birth cohort, period, and age as determinants of the observed time trends. RESULTS: For the overall age-adjusted incidence rates, squamous cell carcinoma and small cell carcinoma have stabilized in men, whereas they are still increasing in women. The incidence of adenocarcinoma has been increasing in both men and women, but there has been a much sharper incidence among females since the mid-1970s. An examination of age-specific incidence rates by birth cohort and the results from age-period-cohort modeling indicate that incidences of all three major histologic types of lung cancer in the recent birth cohorts either have started decreasing (squamous cell carcinoma) or shown a clear reduction in the rate of increase (adenocarcinoma and small cell carcinoma). This study, however, did not indicate an increase of bronchoalveolar lung carcinoma, which was reported by other clinically based studies. CONCLUSION: While the overall age-adjusted incidence rates showed different incidence patterns for different histologic types of lung cancer, a decreasing or stabilized rate for all three major histologic types of lung cancer was observed in recent birth cohorts in both males and females. The observed incidence pattern is consistent with smoking trends over time including changes in smoking prevalence and the consumption of low tar and filter cigarettes. It is expected that if the current trend in tobacco smoking continues and if there are no major changes in other risk factors for lung cancer, a forthcoming stabilization or decrease in the rate of lung cancer incidence for all major histologic types (including adenocarcinoma) in both sexes in Connecticut could be anticipated.

Adenocarcinoma↗
PubMed1994

Time trends in the incidence of renal carcinoma: analysis of Connecticut Tumor Registry data, 1935-1989.

Recent trends in the incidence of renal cancer, stratified by histology, have not been reported. This study utilized data from the Connecticut Tumor Registry (CTR), the oldest population-based cancer registry in the United States, to establish time trends in the incidence of adenocarcinoma and transitional cell carcinoma of the kidney and urinary tract. All 10,209 incident cases of renal cancer reported to the CTR between 1935 and 1989 were analyzed. Regression modelling was employed to determine the effects of age, period, and birth cohort on incidence rates, and to project future trends. The incidence rate of adenocarcinoma increased in females from 0.7/100,000 in 1935-39, to 4.2/100,000 in 1985-89; and in males, from 1.6/100,000 in 1935-39, to 9.6/100,000 in 1985-89. The reported incidence of transitional cell carcinoma increased in males from 0.5/100,000 in 1950-54 to 2.8/100,000 in 1985-89, and in females from 0.2/100,000 to 1.1/100,000 over the same period. Regression modelling revealed that both net and recent drift, the sum of period and cohort slopes, were positive for adenocarcinoma in both sexes, largely due to a positive cohort effect. While the net drift for transitional cell carcinoma was positive, recent drift was negative in both sexes due primarily to a negative cohort effect. Incidence rates of adenocarcinoma are likely to rise in the immediate future, with the rate of rise in females possibly exceeding that in males. Incidence rates of transitional cell carcinoma will stabilize.

Adult↗
PubMed1994

Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation.

Identification of a biocompatible immunoprotective membrane to prevent graft rejection remained elusive until the development of microcapsules formulated in alginate high in guluronic acid. We report insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Encapsulated human islets were injected intraperitoneally in a diabetic patient with a functioning kidney graft. Insulin independence with tight glycaemic control was demonstrated 9 months after the procedure. These results warrant a trial of a high dose of encapsulated islets in early-onset diabetic patients.

Adult↗
PubMed1994

IL-1 and transforming growth factor-beta regulation of fibroblast-derived IL-11.

IL-11 and IL-6 are fibroblast-derived cytokines with overlapping biologic properties. To determine whether IL-11 and IL-6 are similarly regulated, we characterized the effects of rIL-1 and TGF-beta (beta 1 and beta 2) on human lung fibroblast IL-11 production and compared this regulation with that of IL-6. Unstimulated fibroblasts did not produce significant amounts of IL-11, whereas rIL-1 alpha and TGF-beta were dose-dependent stimulators of IL-11 protein production, mRNA accumulation, and gene transcription. rIL-1 alpha and TGF-beta also interacted in a synergistic fashion to further increase IL-11 protein production and mRNA accumulation. The effects of rIL-1 and TGF-beta individually were not altered by the cyclic nucleotide-dependent protein kinase inhibitor HA1004, protein kinase C (PKC) inhibition with staurosporine, or chronic phorbol ester preincubation, or the calmodulin antagonists W7 and TFP. The effects of rIL-1 alpha and TGF-beta in combination were also unaltered by HA1004, staurosporine, and chronic phorbol ester exposure. A23187, however, did induce IL-11 mRNA accumulation and W7 and TFP did reverse the synergistic stimulation caused by rIL-1 and TGF-beta in combination. In contrast with the regulation of IL-11, TGF-beta did not effectively stimulate IL-6 mRNA accumulation, rIL-1 alpha was a more potent stimulator of IL-6 than IL-11 production, and rIL-1-induced IL-6 mRNA accumulation was augmented by W7 and TFP. These studies demonstrate that: 1) rIL-1, TGF-beta, and agents that increase intracellular calcium stimulate lung fibroblast IL-11; 2) the IL-11 stimulatory effects of rIL-1 and TGF-beta are, at least partially, transcriptionally mediated and are the result of signal transduction pathways that are largely PKC, cyclic nucleotide, and calmodulin independent; and 3) rIL-1 and TGF-beta interact in a synergistic fashion to further increase fibroblast IL-11 production and that this synergy is mediated by a largely PKC- and cyclic nucleotide-independent and calmodulin-dependent activation pathway. Importantly, they also demonstrate that rIL-1 and TGF-beta stimulate lung fibroblast IL-6 and IL-11 production via distinct and differentially regulatable activation pathways.

Calcimycin↗
PubMed1994

Retinoic acid inhibition of IL-1-induced IL-6 production by human lung fibroblasts.

IL-6 is a multi-functional cytokine that plays an important role in normal biologic homeostasis and disease pathogenesis. Retinoids are vitamin A analogs that regulate the function of a wide variety of inflammatory and structural cells. To further understand the biology of retinoids and IL-6 we determined whether all-trans-retinoic acid (RA) and other retinoids regulate lung fibroblast IL-6 production. RA did not stimulate fibroblast IL-6 production. Instead, it inhibited the production of IL-6 by IL-1-stimulated cells. This effect was dose-dependent with an IC50 of 10(-7) M RA and significant inhibition being noted with doses of RA as low as 10(-8) M. These inhibitory effects could not be explained by cytotoxicity or a shift in the kinetics of IL-6 production. They also did not appear to involve alterations in the early events in IL-1-induced IL-6 production, because RA inhibited IL-6 production even when added 6 h after IL-1 and RA did not inhibit IL-1 binding to cell surface IL-1 receptors. RA inhibition of IL-6 protein production was associated with a comparable decrease in IL-6 mRNA accumulation and gene transcription. 13-cis-retinoic acid, retinol, retinaldehyde, all-trans etretin, Ro 13-6298, and 9-cis retinoic acid also inhibited IL-1-induced IL-6 production. However, 4-hydroxyphenyl retinamide and etretinate did not share this property. The inhibitory effects of these analogues may be mediated by nuclear retinoic acid receptors as mRNA encoding RAR-alpha, RAR-gamma, and RXR-alpha were present, and RAR-beta was induced by RA in human lung fibroblasts. These studies demonstrate that RA and other retinoid analogs inhibit IL-1-induced IL-6 production and that this effect is analog-specific and, at least partially, transcriptionally mediated.

Cell Line↗
PubMed1994

Malignant melanoma incidence in Connecticut (United States): time trends and age-period-cohort modeling by anatomic site.

This study examined time trends and age-period-cohort patterns in the incidence of cutaneous malignant melanoma (CMM) by gender and anatomic site in Connecticut (United States) between 1950 and 1989, using data from the population-based Connecticut Tumor Registry. A total of 8,249 invasive CMM incident cases were included. Cases were grouped into melanomas of the head and neck, upper limb, lower limb, and trunk. Between 1950 and 1989, rates increased substantially for all sites. The largest relative increases occurred in melanoma of the upper limb for both males and females; the largest absolute increase occurred for melanoma of the trunk in males; and the smallest increase occurred in head and neck melanoma in females. Recent trends for time periods 1970-89 among birth cohorts 1930-69 indicated that the rate of increase of CMM is slowing substantially among males, but not among females. Nevertheless, continued overall increases in CMM incidence are likely in Connecticut in the 1990s in both genders, with a decrease in the male-female ratio. The age-period-cohort patterns were significantly different between the genders and among anatomic sites, suggesting different trends in carcinogenic exposures (mainly ultraviolet radiation from the sun) or etiologic distinctions between males and females and among the sites.

Adult↗
PubMed1994

Cytokine-cytokine synergy and protein kinase C in the regulation of lung fibroblast leukemia inhibitory factor.

Studies were undertaken to characterize the cytokines and cytokine-cytokine interactions that stimulate human lung fibroblast leukemia inhibitory factor (LIF) production and the mechanisms of these regulatory effects were investigated. Unstimulated fibroblasts did not produce significant amounts of LIF, whereas recombinant interleukin-1 alpha (rIL-1 alpha), transforming growth factor-beta (TGF-beta), and recombinant tumor necrosis factor (rTNF) were dose-dependent stimulators of LIF production. TGF-beta and rIL-1 alpha also interacted in a synergistic fashion to further increase LIF elaboration. Under all conditions alterations in LIF production were associated with comparable alterations in LIF mRNA accumulation. The kinetics of mRNA induction, however, differed with rIL-1-induced LIF mRNA being readily detected after 2 h, TGF-beta 1 induction peaking after 16-24 h, and the induction caused by rIL-1 alpha plus TGF-beta 1 being most prominent after 2-4 h and decreasing with additional incubation. Protein synthesis was not required for LIF induction. In addition, even though A23187 was an effective stimulator of LIF production, the calmodulin antagonists W-7 and trifluoperazone dichoride (TFP) did not significantly alter the LIF-stimulatory effects of IL-1 and TGF-beta. PKC did appear to play an important role in this induction, however, since LIF was induced by PMA and cytokine induction of LIF production was markedly diminished by chronic phorbol ester preincubation, staurosporine, and H-7, but not by HA1004. These studies demonstrate that 1) rIL-1, TGF-beta, TNF, agents that increase intracellular calcium and agents that activate PKC, stimulate lung fibroblast LIF production; 2) rIL-1 and TGF-beta interact in a synergistic fashion to further increase fibroblast LIF production; and 3) rIL-1 and TGF-beta stimulate lung fibroblast LIF production via a pretranslational activation pathway that is largely PKC-dependent and protein synthesis-, cyclic nucleotide-, and calmodulin-independent. Cytokine-stimulated LIF production may play an important role in homeostasis and repair in the human lung.

Cytokines↗
PubMed1993

Developmental expression of the alpha 6 GABAA receptor subunit mRNA occurs only after cerebellar granule cell migration.

Using a competitive polymerase chain reaction (PCR) and appropriate internal standards, we have analyzed absolute amounts of the alpha 6 GABAA receptor subunit mRNA in the postnatally developing cerebellum and neocortex. The PCR data have shown that absolute amounts of the alpha 6 receptor subunit mRNA in the cerebellum increase dramatically (nearly 100-fold) during the second postnatal week, reaching maximal levels by postnatal day 21 (1 fmol/microgram total RNA). The absolute amount of the alpha 6 GABAA receptor subunit mRNA in the cortex at postnatal day 1 was 2 amol/microgram total RNA and increased to 7 amol/micrograms total RNA by postnatal day 14. No further increase in alpha 6 mRNA expression in the adult cortex was observed. Microscopic analysis of emulsion coated and counterstained sections indicated that alpha 6 GABAA receptor subunit mRNA labeling was only detected in the internal granule cell layer and not in either the external granule cell layer or in migrating granule cells. The alpha 1 GABAA receptor subunit mRNA increased in the cerebellar cortex with a similar temporal profile, although its distribution extended to additional cell types (Purkinje cells, stellate/basket cells and possibly cerebellar astrocytes). The temporal expression of these two GABAA receptor subunit mRNAs is coincident with the formation of synaptic contacts in the granule cell dendrites suggesting that afferent pathways innervating these neurons following cell migration may play a critical role in increasing the expression of mRNAs encoding the alpha 1 and alpha 6 GABAA receptor subunits.

Aging↗
PubMed1993

The time trend and age-period-cohort effects on incidence of adenocarcinoma of the stomach in Connecticut from 1955-1989.

BACKGROUND: Adenocarcinoma of the gastric cardia has been be increasing in Connecticut, and the risk factors responsible for the increasing incidence are unknown. This study examined the incidence pattern of adenocarcinoma of the gastric cardia and distal stomach in Connecticut during the past decades and identified components of birth cohort, period, and age as determinants of the observed time trends by regression modeling. METHODS: This study was based on all histologically confirmed incident cases of gastric adenocarcinoma reported to the Connecticut Tumor Registry between 1955 and 1989. Stomach cancers were grouped into cancers of the gastric cardia, distal stomach, or unknown/unspecified subsite. Age-adjusted incidence rates were calculated by the direct method standardized to the 1970 United States population. A regression model was used to identify birth cohort, period, and age as determinants of the observed time trends. RESULTS: The results indicated that the incidence rate of adenocarcinoma of the cardia is increasing, particularly in white males, whereas adenocarcinoma of the distal stomach is now decreasing in both sexes in Connecticut. Regression modeling suggests that the increase of adenocarcinoma of the cardia may be explained partly by a birth cohort phenomenon. CONCLUSION: There is little information regarding the risk factors that might be responsible for the observed increasing trend for adenocarcinoma of the cardia, although smoking, alcohol intake, retinol intake, and hiatal hernia have been associated with an increased risk of adenocarcinoma of the cardia or gastric cancer. Considering the different epidemiologic features of adenocarcinoma of the cardia and distal stomach, future analytic studies should separate cancer of the gastric cardia and cancer of the distal stomach in searching for etiologic factors.

Adenocarcinoma↗