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Biomedical subjects

J Han

Publications and source records attributed to J Han.

At least 73 records · Page 4Linked to original sources
PubMed2001

Gene suppression by tristetraprolin and release by the p38 pathway.

Tristetraprolin (TTP) is a zinc finger protein that has been implicated in the control of tumor necrosis factor (TNF) mRNA stability. We show here that TTP protein has a suppressive effect on promoter elements from TNF-alpha and interleukin-8 and that lipopolysaccharide (LPS) stimulation can release this suppression. The release in LPS-stimulated cells was found to be primarily mediated by the p38 pathway because activation of p38 is sufficient to remove the suppressive effect of TTP. Indeed, TTP seems to be a direct substrate of p38 in vivo since it is an excellent substrate of p38 in vitro, and mutation of potential phosphorylation sites in TTP prevents release of the suppression imposed on TNF transcription. We found TTP protein to be present at low levels in the resting macrophage cell line RAW 264.7 and to be quickly induced after LPS stimulation. The kinetics of TTP induction suggests a potential role of TTP as an important player in switching off LPS-induced genes after induction. In conclusion, TTP plays an important role in maintaining gene quiescence, and this quenching effect on transcription can be released by p38 phosphorylation of TTP.

Animals↗
PubMed2001

Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophages.

Although apoptosis has been observed in macrophages during the course of infections, the mechanism of apoptosis in activated macrophages is not fully understood. This study shows that pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD) or t-butyloxycarbonyl-Asp-fluoromethylketone (Boc-D) caused the death of lipopolysaccharide (LPS)-activated macrophages and RAW 264.7 cells with apoptotic features. The apoptosis was also observed in lipoprotein-treated bacteria but not in CpG oligonucleotide- or flagellin-treated macrophages, indicating a difference of cellular responses downstream of different Toll-like receptors. Consistent with the induction of cell death by pan-caspase inhibitors, no activation of known caspases was detected in LPS-ZVAD-treated cells, suggesting an involvement of unknown proapoptotic caspases in the cell death. ZVAD inhibited the activation of extracellular signal-regulated kinase (ERK) and p38 but not of nuclear factor (NF)-kappa B induced by LPS, suggesting that the ZVAD-sensitive molecule lies upstream of the ERK and p38 pathways but downstream of the divergent site of NF-kappa B and mitogen-activated protein kinases. Our results demonstrate that apoptosis of macrophages induced by LPS+ZVAD is independent from the known proapoptotic caspases and suggest that activity of an unidentified ZVAD-sensitive molecule(s) is involved in the survival of LPS-activated macrophages.

Amino Acid Chloromethyl Ketones↗
PubMed2001

p38 MAP kinase modulates liver cell volume through inhibition of membrane Na+ permeability.

In hepatocytes, Na+ influx through nonselective cation (NSC) channels represents a key point for regulation of cell volume. Under basal conditions, channels are closed, but both physiologic and pathologic stimuli lead to a large increase in Na+ and water influx. Since osmotic stimuli also activate mitogen-activated protein (MAP) kinase pathways, we have examined regulation of Na+ permeability and cell volume by MAP kinases in an HTC liver cell model. Under isotonic conditions, there was constitutive activity of p38 MAP kinase that was selectively inhibited by SB203580. Decreases in cell volume caused by hypertonic exposure had no effect on p38, but increases in cell volume caused by hypotonic exposure increased p38 activity tenfold. Na+ currents were small when cells were in isotonic media but could be increased by inhibiting constitutive p38 MAP kinase, thereby increasing cell volume. To evaluate the potential inhibitory role of p38 more directly, cells were dialyzed with recombinant p38alpha and its upstream activator, MEK-6, which substantially inhibited volume-sensitive currents. These findings indicate that constitutive p38 activity contributes to the low Na+ permeability necessary for maintenance of cell volume, and that recombinant p38 negatively modulates the set point for volume-sensitive channel opening. Thus, functional interactions between p38 MAP kinase and ion channels may represent an important target for modifying volume-sensitive liver functions.

Animals↗
PubMed2001

Pan-caspase inhibitor zVAD enhances cell death in RAW246.7 macrophages.

Even though the pan-caspase inhibitor zVAD has been widely used as an anti-apoptotic agent, inefficient prevention or even enhancement of cell death has been reported in certain cells. To further investigate its effects on cell death, three different cell types were exposed to various apoptotic stimuli in the presence or absence of zVAD. In Jurkat cells, zVAD protected against cell death induced by tumor necrosis factor (TNF), sodium nitroprusside (SNP) and etoposide, whereas in L929 cells cell death was increased. In RAW246.7 macrophages, zVAD showed similar effects as in L929 cells. However, unlike L929 cells, in which the cell death by TNF is known to be necrosis, RAW246.7 cells manifested features of apoptosis such as chromatin condensation and nuclear fragmentation. Induction of cell death by zVAD in lipopolysaccharide (LPS)-activated RAW246.7 cells also showed the same features as those observed in SNP- and etoposide-treated cells. Initiation of an apoptotic process by zVAD not only disputes the sole role of caspases in apoptosis but also suggests an anti-apoptotic function of certain caspase(s). Death of LPS-activated macrophages may be controlled by an anti-apoptotic caspase.

Adjuvants, Immunologic↗
PubMed2001

Malignant thymic epithelial tumors: CT-pathologic correlation.

OBJECTIVE: The purpose of our study was to describe and compare the CT and pathologic findings of atypical thymoma and thymic carcinoma. MATERIALS AND METHODS: Twenty-seven consecutive patients (14 men, 13 women ranging in age from 22 to 77 years [mean age, 52 years]) with pathologically proven atypical thymoma (n = 9) and thymic carcinoma (n = 18) constituted the study population. The chest CT findings in each of the 27 patients were reviewed retrospectively in consensus by two chest radiologists. These findings were correlated with pathologic findings. RESULTS: The tumors were located in the anterior mediastinum, and most tumors had a lobulated margin (24/27, 89%). Atypical thymomas were significantly smaller (mean, 4.7 cm) than thymic carcinomas (mean, 7.2 cm) (p = 0.041) on CT. The findings of invasion of the great vessels, lymph node enlargement, extrathymic metastases, and phrenic nerve palsy were seen only in patients with thymic carcinoma. The frequencies of necrosis, intratumoral calcification, pleural effusion, pleural implants, pericardial effusion, and obliteration of the mediastinal fat plane were not significantly different between atypical thymomas and thymic carcinomas (p > 0.05). Various histologic subtypes were included in thymic carcinoma. The tumor necrosis and calcification seen on CT were confirmed at pathologic examination. CONCLUSION: When a large thymic tumor appears with invasion of the great vessels, lymph node enlargement, phrenic nerve palsy, or extrathymic metastases on CT, thymic carcinoma rather than atypical thymoma should be considered.

Adult↗
PubMed2001

Quantification of ground-glass opacity on high-resolution CT of small peripheral adenocarcinoma of the lung: pathologic and prognostic implications.

OBJECTIVE: The purpose of our study was to correlate the high-resolution CT findings of small peripheral adenocarcinoma of the lung with underlying histopathology and to evaluate the prognostic implications of the CT findings. MATERIALS AND METHODS: The high-resolution CT findings of small peripheral adenocarcinoma of the lung in 224 patients were analyzed by two independent observers for location, size, marginal characteristics, and extent of ground-glass opacity and necrosis. The pathologic specimens were reviewed by an experienced lung pathologist. RESULTS: One hundred and thirty-two patients had bronchioloalveolar carcinoma and 92 had adenocarcinoma. The extent of ground-glass opacity was greater in bronchioloalveolar carcinomas (mean +/- SD, 29% +/- 31.6%) than in other adenocarcinomas (8% +/- 13.3%) (p < 0.001). The extent of ground-glass opacity was significantly greater in patients without recurrence (p = 0.020) and those without nodal (p = 0.017) or distant (p = 0.007) metastases than in patients with nodal or distant metastases or in whom the carcinoma had recurred. CONCLUSION: The extent of ground-glass opacity in a nodule is greater in bronchioloalveolar carcinomas than in other adenocarcinomas. Greater extent of ground-glass opacity also correlates with improved prognosis.

Adenocarcinoma↗
PubMed2001

IgG2a and igA co-expression by the natural autoantibody-producing murine B lymphoma T560.

The T560 B lymphoma produces polyreactive IgG2a with the features of natural autoantibody. All T560 cells bear and secrete IgG2a but a small fraction spontaneously co-express IgA. Cells secreting IgA alone cannot be detected. IgA secretion is enhanced by interaction of T560 cells either with activated T cells and cognate antigen, or with LPS, but not with cytokines, including IL-5 and TGF-beta. IgA and IgG2a mRNAs have identical V186.2. DFL 16 and JH1 sequences from framework 2 through JH1. PCR analysis reveals that previous recombination events have led to deletion of the mu, gamma3, gamma1, gamma2b constant region genes from both the productive and the unproductive chromosome but the former has retained gamma2a, epsilon and alpha, the latter only alpha. Digestion-circularization (DC)-PCR experiments provide formal proof of DNA recombination between Ca and the intron upstream of Cmu. Evidently, the productive chromosome has switched only as far as gamma2a, the unproductive all the way to the alpha constant region gene. The unproductive allele is transcriptionally active as evidenced by the presence of mRNA encoding Calphal inappropriately spliced to a cryptic splice site in the downstream intron of DQ52 (eliminated from the productive chromosome). A specific RT-PCR using oligonucleotide primers derived from the upstream initiation site of the Ialpha exon and from Calpha1 discloses that T560 cells contain alpha-germ line mRNA, presumably transcribed from the Ialpha-region of the productive chromosome, spliced to Calpha. Treatment with LPS stops production of these spliced transcripts suggesting that it may promote either DNA recombination in cells spontaneously transcribing Ialpha or a change in splicing such that Ialpha sequence is no longer joined to Calpha. Verification of the DC-PCR product by sequencing reveals that the T560 and B10.A IgA (Ig2b allotype) hinge is different from the BALB/c IgA (Ig2a allotype) hinge: it has two extra Cys and has eliminated the first Thr, a potential glycosylation site in BALB/c IgA.

Animals↗
PubMed2001

Focal organizing pneumonia: CT and pathologic findings.

The purpose of this study was to describe the CT findings of focal organizing pneumonia and to compare the findings with pathology. CT findings of histologically proven focal organizing pneumonias in 26 consecutive patients were analyzed. In 17 patients who had undergone surgical resections, the findings were correlated with pathology. Focal organizing pneumonias appeared as a nodule (n= 13) or a mass (n=13), ranging from 9 mm to 66 mm in diameter. Ground-glass opacity was seen in 6/13 (46%) nodules and 6.5/13 (50%) masses (k=.48) with an extent ranging from 5% to 75% (mean, 16%). In 4/26 (15%) patients, the extent was more than 50% of the lesion. They showed smooth (n=4), lobulated (n=8), spiculated (n=1), or lobulated and spiculated margin (n=13). On correlative analysis, nodule or mass on CT consisted histologically of intraalveolar exudate or microabscess, chronic inflammatory cell infiltration, fibrotic nodules, and polypoid granulation tissue in the alveolar or bronchiolar spaces. Ground-glass opacity consisted of interstitial fibrosis and chronic inflammatory cell infiltration and intraalveolar polypoid granulation tissue. Focal organizing pneumonia may simulate a lung cancer with variable appearances on CT and the findings reflect underlying histopathology of the disease.

Adult↗
PubMed2001

Development of cataractous macrophthalmia in mice expressing an active MEK1 in the lens.

PURPOSE: To characterize the extracellular signal-regulated kinase (ERK) pathway in the lens and to try to understand how this pathway contributes to lens function and cataractogenesis. METHODS: The members of the ERK pathway in the lens were examined by Western blotting, immunohistochemical staining, and kinase assay. A gain-of-function approach was used to perturb the ERK pathway in the lenses of transgenic mice via expression of a constitutively active mutant of the mitogen-activated protein kinase kinase 1 (MEK1(E)), the direct upstream kinase of the ERK1 and ERK2 kinases, under the alphaA-crystallin promoter. RESULTS: The presence of an active ERK pathway was found in lens epithelial cells and in differentiating fibers. Transgenic mice that expressed MEK1(E) developed postnatal cataracts as well as macrophthalmia. Distinct morphologic alterations, such as lens enlargement, swelling fiber cells, enlarged extracellular space, and vacuole formation, were observed in the lenses of these transgenic mice. A significant increase in the glucose transporter 1 (GLUT1) level, as well as in the glucose level, was detected in the lens. CONCLUSIONS: The MAP kinase pathway is involved in the regulation of glucose metabolism and balance in the mouse lens. Moreover, the alteration of MAP kinase activity in the lens is sufficient to cause cataract formation with enlarged extracellular space and vacuoles in the differentiating fibers. This transgenic mouse may provide a useful model for understanding the mechanism(s) for some aspects of human cataracts.

Animals↗
PubMed2001

[Effect of zinc on the activities of ATPase of erythrocyte membrane].

The effects of zinc on the activities of Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase of erythrocyte membrane were studied both in vivo and in vitro. Male adult rats were divided into three groups and fed on diets with different concentration of zinc (2.2, 28 and 128 mg/kg diet). Eight rats of each group were sacrificed after 25 days and the activities of the two ATPase were measured. The rest rats were changed diet for an other seven days to detect the sensitivities of the ATPases. The activities of these ATPase were also determined in fresh human erythrocyte membrane treated with different concentration of zinc (0, 5, 10, 50, 100, 500 mumol/L). The results showed that the activities of both Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase were in close relationship with zinc concentration, too low or too high zinc could decrease them. Compared with Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase was more sensitive to zinc deficiency and in a slower reaction to zinc supplement, but it could stand higher zinc concentration. It was concluded that zinc played an important role on maintaining the normal activities of Na+, K(+)-ATPase and Ca2+, Mg(2+)-ATPase.

Animals↗
PubMed2001

The role of factor XI in a dilute thromboplastin assay of extrinsic coagulation pathway.

Blood coagulation has been thought to be composed of both intrinsic and extrinsic pathways. Recent evidence strongly supports the critical role of the extrinsic pathway in the initiation of blood coagulation. This investigation established an assay that examines the role of FXI in the thromboplastin-initiated (extrinsic) coagulation based on this new concept. Plasma clotting times were measured at different concentrations of thromboplastin with activated FXII inhibited (FXIIa-inhibited Diluted Thromboplastin Time, FXIIaiDTT). Only at low concentrations of thromboplastin was FXIIaiDTT of FXI-deficient plasma significantly prolonged than that of normal plasma. Depletion of FXI from normal plasma prolonged its FXIIaiDTT and replenishment of FXI shortened it. FXIIaiDTTs of both FVIII-deficient and FIX-deficient plasma were remarkably prolonged, and addition of normal plasma dose-dependently shortened it. Furthermore, earlier alpha-thrombin inhibition was directly correlated with decreasing FXa generation. The amount of FXa production was: platelet-rich plasma > platelet-poor plasma > FXI-deficient plasma. Therefore, our findings from the FXIIaiDTT assays not only support the critical role of extrinsic pathway in blood coagulation initiation, but also demonstrate the importance of FXI as an amplifier of thrombin generation in thromboplastin-initiated coagulation.

Blood Coagulation↗
PubMed2001

[Manufacture and study of porous poly(l-lactic acid) (PLLA)/beta-tricalcium phosphate (beta-TCP) composite].

A promising alternative to supply bone substitutes is to develop living tissue substitutes based on biodegradable materials, which is called bone tissue engineering. One of the research high-lights of bone tissue engineering is to design and manufacture scaffolds for cell attaching, migrating, and proliferating. A process which consists of a solvent casting stage, a compression molding stage and a leaching stage has been used to fabricate macroporous composites of poly(l-lactic acid) (PLLA) and beta-tricalcium phosphate (beta-TCP). The effects of the weight fraction of porogen--NaCl, of the weight ratio of PLLA to beta-TCP and of the diameters of beta-TCP on the porosities, the average pore diameters and the compressive yield strength and compressive modulus have been studied. The results showed that the porosities and the average pore diameters increased and the compressive yield strength and modulus decreased when the weight fraction went from 50% to 90%. The compressive yield strength and compressive modulus could be improved by changing the weight ratio of PLLA to beta-TCP and the diameters of beta-TCP in low-porosity composites (lower than 70%). But high-porosity composites (90%) were not reinforced by changing the weight ratio.

Biocompatible Materials↗
PubMed2001

[Intratumoral injection of macroaggragated albumin and colloidal 32P for the treatment of hepatocellular carcinoma].

OBJECTIVE: To study the tumor deposition and systemic distribution of colloidal (32)P in single colloidal (32)P injection and macroaggragated albumin (MAA) injection followed by colloidal (32)P and to evaluate their clinical effects and side effects for the treatment of hepatocellular carcinoma. METHODS: H(22) hepatocellular cancer cells were inoculated subcutaneously in the right fore leg of Balb/c mice. When the tumors reached to 1.0 cm in diameter about 10 days postinjection, the mice were divided into two groups randomly. In the first group, the tumors were only injected with 1.85 MBq of colloidal (32)P; while in the second group, with 1 +/- 10(5) particles of MAA followed by 1.85 MBq of colloidal (32)P. The radioactivity in the tumor, blood, heart, liver, kidney, spleen, and bone of each animal was determined at 30min, 24 h, 48 h, 8 d, and 16 d postinjection. Histopathology of tumors was observed at 16 d and 1 month postinjection. The ultrasound-guided intratumoral injection of MAA and colloidal (32)P was performed on 30 patients with hepatocellular cancer. The evaluation of efficacy and side effects was made on the basis of clinical manifestations, histopathological changes, variations in tumor size, serum AFP, the functions of heart, liver, kidney, blood routine, and immune functions before and after the treatment. RESULTS: Intratumoral injection of colloidal (32)P resulted in necrosis and fibrosis of the tumor cells. Pretreatment with MAA before administration of colloidal (32)P effectively decreased the diffusion of colloidal (32)P from the tumor to blood, and led to retention of colloidal (32)P in the tumor for a longer time. After treatment, a significant shrinkage of the tumor size was seen in all cases with the average shrinkage rate of 53.25%. Serum AFP values decreased remarkably. Clinical symptoms alleviated. The survival rate of 1, 2, and 3 years was 90%, 76.67%, 43.33%. No side effect was found. CONCLUSIONS: Intratumoral injection of MAA and colloidal (32)P is a simple, safe, and effective alternative for the treatment of hepatocellular cancer.

Adult↗
PubMed2001

Cellular responses to tumor necrosis factor.

TNF is a proinflammatory cytokine that plays an important role in many physiological and pathological conditions through the regulation of immunological reactions. Many of TNF functions have been proven to be cell type-specific, and the specificity of TNF-induced cellular responses in a given cell is determined by the specific intracellular signaling pathways that are activated by TNF. Although current information is insufficient to sort out how the cell type specificity is controlled by the different intracellular signaling pathways, a number of signaling pathways that are commonly activated in many types of cells by TNF have been revealed. This review weighs the current knowledge of these TNF-induced signaling pathways.

Animals↗
PubMed2001

[The prevalence of beta-thalassemia heterozygotes compound alpha-thalassemia in Guangdong district].

OBJECTIVE: To investigate the prevalence of beta-thalassemia (beta-thal) heterozygotes compound alpha-thal in Guangdong area. METHODS: alpha-thal 1 genes were amplified in 500 beta-thal carriers diagnosed by reverse dot blotting (RDB) using gap-PCR method, alpha-thal 2 genes were detected in 400 of the 500 beta-thal carriers using Southern blotting with alpha-globin DNA probe and restrict endonuclease zymogram analytical method. RESULTS: Forty three alpha-thal-1(alpha alpha/- -SEA) cases were identified in the 500 beta-thal traits, and 26 alpha-thal 2 including 17 rightward deletion (alpha alpha/- alpha 3.7) and 9 leftward deletion(alpha alpha/-alpha 4.2) cases were identified in the 400 beta-thal traits. CONCLUSION: The prevalence of beta-thal heterozygote carrying alpha-thal-1 gene was 8.6% and that of beta-thal heterozygote carrying alpha-thal-2 gene was 6.5% (4.2% rightward deletion and 2.2% leftward deletion).

Adult↗
PubMed2001

[Clinical and pathological analysis on 106 cases with uterine sarcoma].

OBJECTIVE: To analyze the clinical features and factors affecting the prognosis of uterine sarcoma with different histological types. METHODS: One hundred and six cases with uterine sarcoma treated were analyzed retrospectively, among which there were 67 cases with leiomyosarcoma (63.2%), 23 with malignant endometrial interstitial sarcomas (21.7%), 16 with malignant Mullerian mixed tumor (15.1%). According to Union Internationale Contre le Cancer (UICC) staging, 70 cases were on stage I, 12 cases were on stage II, 19 cases belonged to stage III, and 5 cases belonged to stage IV. RESULTS: (1) The patients with leiomyosarcoma and endometrial interstitial sarcoma were relatively younger, the patients of them aged under 50 amounted to 70.1% (47/67) and 60.9% (14/23) respectively, and those aged under 40 amounted to 29.9% (20/67) and 39.1% (9/23) respectively. The patients usually manifested with abnormal vaginal bleeding (67.0%), palpable mass of lower abdomen (32.1%), vaginal discharge (27.4%), pain on lower abdomen (28.4%), symptoms of oppression (25.5%), and discomfort feeling (28.3%). (2) The rate of preoperative diagnosis was 65.9%, especially that of leiomyosarcoma was lowest (42.9%). (3) In treatment, 16.0% of patients was treated by hysterectomy; bilateral salpingo-oophorectomy and pelvic lymphadenectomy; 75.5% of them by hysterectomy and bilateral salpingo-oophorectomy; after operation, 74.5% of them were treated by chemotherapy, 11.3% by radiotherapy, 6.6% by additional progesterone. (4) The survival period of the patients was related to pathologic types and clinical stages and ages of the patients. The prognosis of the patients with leiomyosarcoma younger earlier stage was better. CONCLUSIONS: The clinical symptom of uterine sarcoma is nonspecific (mostly abnormal vaginal bleeding) and the prognosis is poor. The patients with leiomyosarcoma are younger and have better prognosis, but the rate of preoperative diagnosis is low. The prognosis of uterine sarcoma is related to pathologic types, clinical stage and ages of the patients.

Adult↗