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Biomedical subjects

D G Li

Publications and source records attributed to D G Li.

At least 19 recordsLinked to original sources

A mimotope of pre-S2 region of surface antigen of viral hepatitis B screened by phage display.

To acquire the phage-displayed mimotopes which mimic the specificity of hepatitis B virus surface antigen (HBsAg), a random peptide library expressing linear peptide with 12 amino acids in length were used to screen with the serum from a hepatitis B virus infected patient in the recovery phase. After 3 rounds of biopanning, the positive phages were confirmed by competitive ELISA using HBsAg/P33. Two phagotopes were identified and one of them was confirmed as mimotope by competition experiment. Based on the mimotpe, a multiple antigenic peptide with four branches was synthesized by solid phase peptide synthesis. The antiginicity and specificity of the synthesized antigen was tested in BALB/c mice compared with the native epitope-based antigen. The results showed that the mimotope-based antigen could evoke higher titer of antibodies with the same specificity of the epitope-based antigen. Those findings indicate mimotopes can be used in antigen and vaccine design.

Animals↗

Expression changes of activin A in the development of hepatic fibrosis.

AIM: To examine the expression of activin A, a member of the transforming growth factor (TGFbeta) superfamily, recently has been reported to be overexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enhanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 +/- 0.094 vs 0.2860.0670, P< 0.01; 0.620 +/- 0.134 vs 0.286 +/- 0670, P< 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas. CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period.

Activins↗

A cohort study of cancer among benzene-exposed workers in China: overall results.

A large cohort study of 74,828 benzene-exposed and 35,805 unexposed workers employed between 1972 and 1987 in 12 cities in China were followed to determine mortality from all causes and the incidence of lymphohematopoietic malignancies and other hematologic disorders. Benzene-exposed study subjects were employed in a variety of occupations, including painting, printing, and the manufacture of footwear, paint, and other chemicals. All-cause mortality was similar in the benzene-exposed and unexposed comparison group. Statistically significant excess deaths were noted among benzene-exposed subjects for leukemia (RR = 2.3, 95% CP 1.1-5.0), malignant lymphoma (RR = 4.5, 95% CI: 1.3-28.4), and nonneoplastic diseases of the blood (RR = 95% CP 2.5-infinity), and a marginally significant excess was noted for lung cancer (RR = 1.4, 95% CI: 1.0-2.0). Risk was significantly elevated for the incidence of all lymphohematopoietic malignancies (RR = 2.6, 95% CI: 1.5-5.0), malignant lymphoma (RR = 3.5, 95% CI: 1.2-14.9), and leukemia (RR = 2.6, 95% CI.. 1.3-5.7). Among the leukemia subtypes, only acute myelogenous leukemia (AML) incidence was significantly elevated (RR = 3.1, 95% CI: 1.2-10.7), although nonsignificant excesses were also noted for chronic myelogenous leukemia (CML) (RR = 2.6, 95% CI: 0.7-16.9) and lymphocytic leukemias (RR = 2.8, 95% CI.. 0.5-54.5). Significant excesses were found for aplastic anemia (RR = infinity, 95% CI: 2.2-co) and myelodysplastic syndrome (RR = infinity, 95% CI: 1.7-infinity). Employment in benzene-associated occupations in China is associated with a wide spectrum of myelogenous and lymphocytic malignant diseases and related disorders. Investigations continue to assess the nature of these associations.

Adult↗

Heat shock protein expression in human placenta and umbilical cord.

We examined the level of heat shock proteins (HSPs) present in umbilical cord vessels and placenta following delivery. A 10 cm segment of fresh umbilical cord was obtained immediately after delivery and a placental biopsy was obtained following the third stage of labor. Apgar scores, cord pHs, and pertinent histories were recorded. Tissues were prepared and analyzed for HSP mRNA by in situ hybridization, Western blot, and immunohistochemistry. Sixteen patients were studied. HSP72 mRNA was selectively expressed in the vascular smooth muscle in all cord arteries and veins. This correlated with marked expression of HSP72 protein in the vascular media. Both HSP72/73 mRNA and protein expression were noted diffusely in the placenta. HSP27 protein was highly expressed in umbilical cords with lower levels present in placentas. There were no correlations between method of delivery, gestational age, Apgar score, cord pH, or fetal outcome to the magnitude or distribution of the HSP response. This is the first demonstration of HSP expression in the human maternal-fetal circulation.

Blotting, Western↗

An expanded cohort study of cancer among benzene-exposed workers in China. Benzene Study Group.

An expanded cohort study of 74,828 benzene-exposed and 35,805 unexposed workers were followed during 1972 to 1987, based on a previous study in 12 cities in China. A small increase was observed in total cancer mortality among benzene-exposed compared with unexposed workers (relative risk [RR] = 1.2). Statistically significant excesses were noted for leukemia (RR = 2.3), malignant lymphoma (RR = 4.5), and lung cancer (RR = 1.4). When risks were evaluated by leukemia subtype, only acute myelogenous leukemia was significantly elevated (RR = 3.1), although nonsignificant excesses were also noted for chronic myelogenous leukemia (RR = 2.6) and acute lymphocytic leukemia (RR = 2.3). A significant excess was also found for aplastic anemia.

Anemia, Aplastic↗

Mortality among benzene-exposed workers in China.

A large cohort of 74,828 benzene-exposed and 35,805 nonexposed workers employed between 1972 and 1987 in 12 cities in China was followed to determine mortality from all causes. Benzene-exposed study subjects were employed in a variety of occupations including coating applications, and rubber, chemical, and shoe production. Mortality was slightly increased among workers with greater cumulative exposure to benzene (ptrend < 0.05), but this excess was largely due to cancer deaths (ptrend < 0.01). Deaths due to lymphatic and hematopoietic malignancies (ptrend = 0.01) and lung cancer (ptrend = 0.01) increased with increasing cumulative exposure to benzene. Investigations continue to relate benzene exposure to specific lymphatic and hematopoietic malignancies and other causes of death.

Benzene↗

Clinical features of hematopoietic malignancies and related disorders among benzene-exposed workers in China. Benzene Study Group.

Previous occupational cohort studies of benzene-exposed workers have for the most part used only death certificates to validate diagnoses of workers developing leukemia and other hematopoietic and lymphoproliferative malignancies and related disorders (HLD). In a follow-up study of 74,828 benzene-exposed workers and a comparison group of 35,805 nonexposed workers from 12 cities in China, we sought to characterized clinicopathologically and to confirm diagnoses of all cases of HLD. Using medical records, laboratory hematology results, and histopathology, U.S. and Chinese expert hematopathologists, blinded to exposure status, carried out a detailed review using standardized evaluation forms. Key among the findings were a notable diversity of malignant and nonneoplastic hematopoietic and lymphoproliferative disorders, documentation of excess myelodysplastic syndromes among benzene workers, and widespread dyspoiesis involving all hematopoietic cell lines. As sophisticated clinicopathologic characterization and corresponding classification schemes for HLD become increasingly widespread, it is recommended that future epidemiologic investigations of benzene workers incorporate similarly detailed morphologic evaluation. In extending follow-up of this cohort of young workers, we will continue to use all available clinical, laboratory hematology, and pathology data as well as cytogenetic and biochemical markers to characterized various HLD outcomes. These careful surveillance mechanisms should also provide additional insight into carcinogenic mechanisms of benzene and allow comparison of the molecular pathogenesis of HLD induced by benzene versus chemotherapy, radiation, or other exposure.

Adult↗

Effects of egtazic acid and calcimycin on synthesis of DNA and collagen in cultured human lung fibroblasts.

AIM: To study the effects of egtazic acid (EA) and calcimycin (Cal) on the synthesis of DNA and collagen in cultured human lung fibroblasts (HLF). METHODS: The synthesis of DNA and collagen was determined by measuring the incorporation of [3H]TdR and [3H]proline of HLF respectively. RESULTS: The collagen synthesis increased markedly 24 h after exposure to both EA (0.05-4 mmol.L-1) and Cal (0.25-20 mumol.L-1), and that there was no obvious change in DNA synthesis. After 36-48-h exposure, both DNA and collagen syntheses decreased in the groups of EA (1, 2, and 4 mmol.L-1); the DNA synthesis was also suppressed in Cal groups in a concentration-dependent manner, whereas collagen synthesis decreased only in Cal (10 and 20 mumol.L-1). CONCLUSION: Extracellular Ca2+ influx into fibroblasts increased collagen production, However, the DNA synthesis was suppressed when the cytosolic Ca2+ was too high or too low.

Biological Transport, Active↗

Acute hypertension induces heat-shock protein 70 gene expression in rat aorta.

BACKGROUND: Many factors cause acute systemic hypertension, which in turn can result in damage to the vessel wall and lead to vascular disease. In previous studies, we demonstrated that restraint, or immobilization stress, results in the induction of heat-shock protein 70 (hsp70) gene expression in the aorta of adult rat and showed that this response was markedly attenuated with age. METHODS AND RESULTS: Here we provide evidence that restraint-induced hsp70 expression occurs secondary to a rise in systemic blood pressure. Old rats were unable to mount a significant stress-induced hypertensive response, providing an explanation for the reduced hsp70 response in the old rats. A variety of vasoactive agents that induce acute hypertension through distinct signal transduction pathways, including phenylephrine, dopamine, vasopressin, angiotensin II, and endothelin-1, were found to result in hsp70 mRNA induction in the aorta. The magnitude of hsp70 expression achieved with these hypertensive agents was directly correlated with their relative effects on blood pressure. Rats were treated with the vasodilator sodium nitroprusside, which prevented an acute rise in blood pressure from the hypertensive agents tested and abolished induction of hsp70 expression. CONCLUSIONS: These findings support the conclusion that hsp70 induction occurs as a physiological response to acute hypertension and suggest the possibility that hsp70 plays a role in the protecting the vasculature from damage during hemodynamic stress.

Aging↗

Aortic crosstransplantation between young and old rats: effect upon the heat shock protein 70 stress response.

In previous studies we demonstrated that restraint, or immobilization stress, resulted in the induction of HSP70 mRNA in the vasculature of rats. This response was confined to the vascular smooth muscle, was associated with alpha 1-adrenergic receptor stimulation, and was attenuated with age. In the present study, we examined the influence of transplanting aged vessels into young animals and young vessels into aged animals to determine if this age-related diminution was due to changes intrinsic to the aorta or the result of alterations in the environment in which the aorta resides. We demonstrate that restraint-induced HSP70 expression in transplanted vessels is influenced to a greater degree by the age of the recipient than by the age of the transplanted vessel. Transplantation of aged vessels into young animals leads to preservation of the response, whereas transplantation of young vessels into aged animals leads to attenuation. These findings indicate that the environment in which the vessel resides is a major factor in determining this molecular response to stress.

Aging↗

Effects of tetrandrine and chlorpromazine on synthesis of collagen and hyaluronic acid in cultured human lung fibroblasts.

AIM: To study the effects of tetrandrine (Tet) and chlorpromazine (Chl) on synthesis of collagen and hyaluronic acid (HA) in cultured human lung fibroblasts (HLF). METHODS: The synthesis of collagen and HA was assessed by measuring the incorporation of [3H]proline and radioimmunoassay. RESULTS: Both Tet (5-80 mumol L-1) and Chl (10-40 mumol L-1) diminished the collagen synthesis in a concentration-dependent manner. The suppression was aggravated at 36-48 h. The HA content in the supernatant of culture also decreased gradually with the increasing dosage of Tet or Chl after 24-h exposure. There was no obvious toxic effect of Tet on HLF cells at 5-20 mumol L-1. CONCLUSION: Tet 5-20 mumol L-1 decreased the production of collagen and HA without obvious toxity on HLF, suggesting that Tet could be a hopeful anti-fibrosis drug.

Alkaloids↗

[Relationship between Helicobacter pylori infection other factors and diffuse-and intestinal type stomach carcinomas].

To investigate the role of Helicobacter Pylori (HP) infection and other factors in the development of stomach carcinoma, a matched case-control study was conducted in Dalian, China. A total number of 95 paired cases and controls were involved in the study. The cases were divided into two histological types: diffuse- and intestinal-type. IgG antibody of HP in the subjects was tested with ELISA method. The results revealed that the prevalences of HP infection in cases and in controls were 77.5% and 50.0%, respectively, and that the matched OR was 5.0 (2.08-12.01). The stratified analysis showed that the risk effect of HP in intestinal-type was more significant (OR = 5.75, 1.99-16.63) than it in defuse-type (OR = 3.5, 0.73-16.89). Cancer history within family and blood group A were associated with diffuse-type while the environmental factors such as low economic status, irregular eating and fast-eating habits were mainly associated with intestinal-type. We conclude from our findings that HP infection may play a role in the development of stomach cancer, especially for intestinal-type gastric cancer. The two Lauren's histological types of stomach cancer might be different in terms of pathogenesis and characteristics.

ABO Blood-Group System↗

Hematopoietic malignancies and related disorders among benzene-exposed workers in China.

Although the relationship between benzene and acute nonlymphocytic leukemia (ANLL) is well established, most of the analytic cohort investigations examining the relationship between benzene and hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a follow-up study of 74,828 benzene-exposed and 35,805 non-exposed workers in China, pathology reports, medical records, and/or histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct classification and to provide clinicopathologic descriptions. Eighty-two patients with hematopoietic neoplasms and related disorders were identified among benzene-exposed workers, including 32 cases of acute leukemia, 7--myelodysplastic syndrome (MDS), 9--chronic granulocytic leukemia (CGL), 20--malignant lymphoma or related disorder (ML), 9--aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were observed, including 6 patients with acute leukemia, 2--CGL, 3--ML, and 2 others. The hematopathologic characteristics of the benzene-exposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatment-related ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to data, also indicate that a greater diversity of hematologic neoplasms is evident among benzene-exposed workers than previously described.

Adult↗

Impaired wound healing in Cushing's syndrome: the role of heat shock proteins.

BACKGROUND: Glucocorticoids impair wound healing and cause surgical morbidity. Heat shock proteins are essential to cellular stress tolerance and are associated with glucocorticoids. The adrenal heat shock protein response is under hypothalmic-pituitary-adrenal-axis control, whereas the vascular response is associated with alpha-1 receptors. Because heat shock proteins affect cellular stress responses and are under hypothalmic-pituitary-adrenal-axis control in other tissues, we postulated an association between heat shock proteins and glucocorticoids in healing wounds. METHODS: Modified Hunt-Schilling wound chambers were implanted subcutaneously in rats. They received subcutaneous time-release dexamethasone (25 mg) or placebo pellets. Wound chamber heat shock protein 25 and heat shock protein 72/73 were serially assayed for 21 days with western analysis and immunocytochemistry. RESULTS: Dexamethasone caused Cushing's syndrome with approximately 10% weekly weight-loss and adrenal atrophy. Total wound tissue decreased 90% with profound differences in molecular wound responses manifested by decreased heat shock protein 25, 72, and 73 in animals treated with dexamethasone despite equal protein loads. Furthermore, dexamethasone caused heat shock protein 72 redistribution by immunocytochemistry. CONCLUSIONS: This study represents the first description of heat shock proteins in a wound healing model and demonstrates tissue-specific decrease of heat shock proteins with glucocorticoid therapy. Thus the heat shock protein response is intimately associated with normal wound healing and is profoundly altered in subjects with Cushing's syndrome. Manipulation of this response may have clinical importance in wound healing.

Adrenal Glands↗

Adrenergic regulation of adrenal and aortic heat shock protein.

BACKGROUND: Surgical stress results in catecholamine secretion and selective induction of the major heat shock protein (HSP70) in the adrenal gland and in the vasculature. The adrenal response is cortical-specific and corticotropin-dependent. The vascular response occurs in the smooth muscle and is corticotropin-independent. We previously suggested that the vascular response was associated with adrenergic receptor stimulation. Herein, we report a series of experiments designed to test the hypothesis that aortic HSP70 messenger RNA (mRNA) induction occurs as a direct and specific response to alpha 1-adrenergic receptor stimulation. METHODS: Acute and chronic indwelling central venous catheter models were developed in the Wistar rat through which the following agents were infused: the alpha 1 agonist phenylephrine (0.14 mg/kg), the beta agonist isoproterenol (0.8 mg/kg), the alpha 1 antagonist prazosin (1 mg/kg), prazosin followed by phenylephrine, or saline solution alone. Hemodynamic responses were monitored; catecholamines were measured by high-performance liquid chromatography; 60 minutes after infusion, the animals were killed, and the adrenal glands and aortas were assayed for HSP70 mRNA expression on Northern blots. RESULTS: Alpha 1 stimulation with phenylephrine resulted in marked hypertension, a reflexive bradycardia, and marked induction of aortic HSP70 mRNA. This effect could be completely abolished when the alpha 1 antagonist prazosin was administered before phenylephrine treatment. The beta agonist isoproterenol failed to induce aortic HSP70. A significant catecholamine response only occurred after prazosin administration. CONCLUSIONS: These studies show a functional interaction between alpha 1 receptor stimulation and vascular HSP mRNA induction.

Adrenal Glands↗

Vascular heat shock protein expression in response to stress. Endocrine and autonomic regulation of this age-dependent response.

Adaptation to stress requires coordinated interactions between the vascular and endocrine systems. Previously we demonstrated that restraint stress induces the expression of the major heat shock protein, HSP70, in the adrenal cortex of the rat. Here we demonstrate that restraint also induces expression of HSP70 in the vasculature. We further demonstrate that the adrenal and vascular responses are differentially regulated: the adrenal response is adrenocorticotropin dependent, whereas the vascular response is under adrenergic control. In addition, the adrenal response is restricted to members of the HSP70 gene family, whereas in vascular tissue the low molecular weight HSP, HSP27, is also induced by restraint. Further characterization of the vascular response revealed that HSP70 induction occurred in both the thoracic and abdominal aortas as well as in the vena cava. However, no HSP70 induction was apparent in the heart or in a wide variety of other tissues examined. In situ hybridization showed that the vascular expression was localized to the aortic smooth muscle cells with minimal expression in the endothelium. Induction of HSP70 mRNA in both the adrenal cortex and aorta was followed by an elevation in HSP70 protein. Maximum HSP70 protein levels were seen within 3-12 h after restraint, but declined thereafter. Stress induced HSP70 expression was dramatically reduced with age, which may explain, in part, the diminished tolerance to stress seen in elderly individuals.

Adrenal Cortex↗

[Significance of serum procollagen-III-peptide in reflecting the therapeutic effects of calcium-channel blockers on hepatic fibrosis].

Changes in serum procollagen-III-peptide (PIIIP) and intravenous tryptophan tolerance test (ITT) were studied in 121 patients with liver cirrhosis during a follow-up period of up to 18 months. The patients received either nifedipine (31 cases, 60 mg/day), verapamil (28 cases, 120 mg/day), cinnarizine (29 cases, 150 mg/day) or tetrandrine (33 cases, 150 mg/day). The significant changes were found in ITT in any of the four drugs administrated for over three months. Serum PIIIP concentration decreased significantly in patients under tetrandrine therapy for 18 months (12.06 +/- 3.91 ng/ml vs 16.57 +/- 5.69 ng/ml before treatment). These data suggest that tetrandrine therapy may have favourable effects on hepatic fibrosis and improvement of liver function in liver cirrhosis.

Adult↗