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Biomedical subjects

H Lu

Publications and source records attributed to H Lu.

At least 307 records · Page 17Linked to original sources

Transforming growth factor-beta response and expression in junctional and oral gingival epithelial cells.

The junctional (JE) and oral gingival (OGE) epithelium show distinct morphological phenotypes and express different cell surface and keratin markers. Transforming growth factor-beta (TGF-beta) has been shown to stimulate extracellular matrix formation and inhibit proteolytic matrix degradation in periodontal wound healing. To elucidate potential roles of TGF-beta in gingival epithelial regeneration and reattachment, the present study examined the effects of TGF-beta on JE and OGE cell growth and determined the patterns of expression of mRNAs for the TGF-beta isotypes beta 1, beta 2 and beta 3 and TGF-beta receptor types I, II and III. Primary cell cultures were initiated from JE and OGE and the cell phenotypes confirmed using monoclonal antibodies to specific keratins. TGF-beta induced a significant growth inhibition in OGE cells derived from 6 different patients with a mean inhibition of 46% and a range of 16-70% (p = 0.031). Although responses varied between patients, in general maximum inhibition occurred at 10 ng/ml TGF-beta. JE cells from 5 patients showed no significant growth inhibition by TGF-beta (p = 0.125). Greater expression of TGF-beta 2 and receptor type I mRNA was found in OGE than JE cells and thus appeared to be associated with differentiating epithelial cells. JE cells expressed more TGF-beta type II receptor specific mRNA than did OGE cells, but TGF-beta 1 mRNA expression was similar in JE and OGE cells. JE or OGE cultures derived from 2 of 3 patients showed expression of mRNA for the TGF-beta type III receptor. TGF-beta 3 mRNA was not detected in any of the JE or OGE samples examined. The greater sensitivity of OGE than JE to the growth inhibiting effects of TGF-beta correlated with higher expression of receptor type I mRNA which, together with the type II receptor, is required for sensitivity to growth inhibition by TGF-beta. The results suggest that, in addition to structural differences, the development of functional differences in the responses of JE and OGE to TGF-beta may be associated with the formation of JE from OGE cells and the reformation of attachment after periodontal surgery.

Antibodies, Monoclonal↗

The initiator element of the adenovirus major late promoter has an important role in transcription initiation in vivo.

Previous results showed that the structure and function of the adenovirus major late promoter (MLP) can be analyzed genetically in its correct location, despite its essential role in the viral life cycle. This genetic approach was extended to investigate the in vivo role of the initiator (INR), a transcriptional element that surrounds the start site of transcription. The analysis was designed to investigate if the INR is an alternative basal element to the canonical TATA box of the MLP, its relative importance in the functioning of the promoter, and if its function was affected by upstream activating elements. Accordingly, two different mutations in the INR were created and tested in the genome, either by themselves or together with mutations in the TATA box or one of the two upstream activating elements, the upstream promoter element (UPE) and the inverted CAAT box. The mutant viruses were examined first in one-step growth experiments, and then levels of late mRNA accumulation were measured by primer extension, transcription initiation was assayed in isolated nuclei, and viral DNA accumulation was determined by Southern hybridization. Neither mutation in the INR alone had any discernible phenotypic effects but when coupled to a phenotypically silent mutation in the TATA box gave rise to viruses with growth defects that were attributable to a significantly lowered rate of transcription initiation from the MLP. These results suggest that the INR plays a role in vivo and can act as an alternative basal element in the absence of a functioning TATA box. A virus with mutations in both the INR and the UPE, although viable, likewise had a severe deficiency in transcription, suggesting that the function of the INR is affected by that of the UPE. This contrasts with the previous report that a TATA box-UPE double mutation is not recoverable in virus. In addition, the virus with mutations in both the INR and the inverted CAAT box was phenotypically wild type, unlike the previously described TATA box-CAAT box double mutant, which had a severe transcription deficiency. Taken together, the present and previous genetic results can be interpreted as evidence that in the MLP, the TATA box and the UPE are the more important of the two basal and activating elements, respectively, but that the INR and CAAT can function in transcription initiation. We consider the role of the INR in the formation of the preinitiation complex and speculate on possible protein-protein interactions.

Adenoviridae↗

The CDK7-cycH-p36 complex of transcription factor IIH phosphorylates p53, enhancing its sequence-specific DNA binding activity in vitro.

Phosphorylation is believed to be one of the mechanisms by which p53 becomes activated or stabilized in response to cellular stress. Previously, p53 was shown to interact with three components of transcription factor IIH (TFIIH): excision repair cross-complementing types 2 and 3 (ERCC2 and ERCC3) and p62. This communication demonstrates that p53 is phosphorylated by the TFIIH-associated kinase in vitro. The phosphorylation was found to be catalyzed by the highly purified kinase components of TFIIH, the CDK7-cycH-p36 trimeric complex. The phosphorylation sites were mapped to the C-terminal amino acids located between residues 311 and 393. Serines 371, 376, 378, and 392 may be the potential sites for this kinase. Phosphorylation of p53 by this kinase complex enhanced the ability of p53 to bind to the sequence-specific p53-responsive DNA element as shown by gel mobility shift assays. These results suggest that the CDK7-cycH-p36 trimeric complex of TFIIH may play a role in regulating p53 functions in cells.

Cyclin-Dependent Kinases↗

Mutations in the conserved C-terminal sequence in thyroid hormone receptor dissociate hormone-dependent activation from interference with AP-1 activity.

A short C-terminal sequence that is deleted in the v-ErbA oncoprotein and conserved in members of the nuclear receptor superfamily is required for normal biological function of its normal cellular counterpart, the thyroid hormone receptor alpha (T3R alpha). We carried out an extensive mutational analysis of this region based on the crystal structure of the hormone-bound ligand binding domain of T3R alpha. Mutagenesis of Leu398 or Glu401, which are surface exposed according to the crystal structure, completely blocks or significantly impairs T3-dependent transcriptional activation but does not affect or only partially diminishes interference with AP-1 activity. These are the first mutations that clearly dissociate these activities for T3R alpha. Substitution of Leu400, which is also surface exposed, does not affect interference with AP-1 activity and only partially diminishes T3-dependent transactivation. None of the mutations affect ligand-independent transactivation, consistent with previous findings that this activity is mediated by the N-terminal domain of T3R alpha. The loss of ligand-dependent transactivation for some mutants can largely be reversed in the presence of GRIP1, which acts as a strong ligand-dependent coactivator for wild-type T3R alpha. There is excellent correlation between T3-dependent in vitro association of GRIP1 with T3R alpha mutants and their ability to support T3-dependent transcriptional activation. Therefore, GRIP1, previously found to interact with the glucocorticoid, estrogen, and androgen receptors, may also have a role in T3R alpha-mediated ligand-dependent transcriptional activation. When fused to a heterologous DNA binding domain, that of the yeast transactivator GAL4, the conserved C terminus of T3R alpha functions as a strong ligand-independent activator in both mammalian and yeast cells. However, point mutations within this region have drastically different effects on these activities compared to their effect on the full-length T3R alpha. We conclude that the C-terminal conserved region contains a recognition surface for GRIP1 or a similar coactivator that facilitates its interaction with the basal transcriptional apparatus. While important for ligand-dependent transactivation, this interaction surface is not directly involved in transrepression of AP-1 activity.

Amino Acid Sequence↗

Actin depolymerization is developmentally regulated in rat type II cells exposed to terbutaline.

The type II alveolar epithelial cell synthesizes and secretes pulmonary surfactant. Terbutaline enhances phospholipid release from adult and fetal type II cells. Our hypothesis is that the actin network of microfilaments regulates the secretory activity of the type II cell. To examine the developmental regulation of the changes in actin subfractions associated with secretory activity, cultures of type II cells derived from adult and 19-d fetal rat lung were incubated with or without 10 microM terbutaline for 1, 30, and 60 min. Dose-response effects of terbutaline were examined in adult type II cells. Effects of phorbol ester were also examined Globular (G-actin) and filamentous (F-actin) fractions were extracted from the cells and analyzed separately. Specified cellular equivalent volumes of each subfraction were analyzed by Western blotting, visualized by a color reaction, and quantified by densitometry. There was a decrease in the cytoskeletal F-actin pool along with an increase in the G-actin fraction within I min in adult type II cells exposed to terbutaline, indicating that depolymerization of F-actin occurs. Values returned to control levels by 60 min. In contrast, the decrease in F-actin, with a concomitant increase in G-actin, was maximal at 60 min in fetal cells exposed to terbutaline. There was a dose-dependent increase in actin depolymerization with maximal effects at 10 microM terbutaline. Phorbol ester also caused an increase in actin depolymerization. Depolymerization of the actin microfilament network may regulate transport and exocytosis of lamellar bodies in type II cells. We speculate that there is an early secretory mechanism that involves depolymerization of actin microfilaments and a late, actin-independent secretory mechanism present in adult type II cells. The timing of the response of the actin-dependent pathway is developmentally regulated. This may explain the developmental differences in the secretion of surfactant that we have previously shown.

Actins↗

Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats.

Obesity and hyperinsulinism are known to be major stimuli of leptin production by adipose tissue, leading to increased leptin levels in the circulation. It has also been demonstrated that increased leptin production leads to satiety, possibly by decreasing the levels of neuropeptide Y (NPY) in the central nervous system (CNS). Because obesity and hyperinsulinism are also frequently associated with hypertension, we studied the effect of the intracerebroventricular (ICV) administration of leptin on mean arterial pressure (MAP), heart rate, vascular flows, and lumbar and renal sympathetic nerve activity (SNA). Normal Wistar rats were implanted with an ICV cannula and allowed to recover. On the day of the study, the animals were fasted and anesthetized with chloralose/urethane. Catheters were placed in a femoral artery and vein, and Doppler flow probes were placed around the iliac, renal, and superior mesenteric arteries for measurement of MAP, heart rate, and blood flows. In other experiments, lumbar SNA and renal SNA were recorded. ICV leptin administration resulted in an MAP that was slowly but progressively increasing. Blood flows decreased in the iliac and superior mesenteric arteries, but not in the renal artery. Leptin injection increased the lumbar SNA and renal SNA. The plasma glucose and insulin levels were not changed. We concluded that ICV leptin increases MAP by decreasing arterial blood flow to the skeletal muscle and the splanchnic vascular bed. This increased peripheral resistance is the result of an increased activity of the sympathetic nerves. We suggest that increased leptin may serve as a link in the triad of obesity and hyperinsulinism and hypertension.

Animals↗

Trends in left ventricular function over three years in the Tecumseh Study.

The relationship between blood pressure and left ventricular diastolic function was examined in participants of the Tecumseh Blood Pressure study. When subjects were divided into three blood pressure groups according to blood pressure levels 3 years apart, it was found that subjects who were had sustained "hypertension" at both time points (SH) had a decreased early/late diastolic filling rate (E/A ratio) compared to subjects who were hypertensive at only one of the timepoints (OH) and those who were consistently normotensive (NN) (1.71 +/- 0.02 NN vs 1.55 +/- 0.05 OH, (p < 0.0001) vs 1.56 +/- 0.07 SH, (p < 0.04)). This relative order was maintained when the second estimation of diastolic filling was performed 3 years later, but the E/A ratio had decreased significantly in all groups (1.54 +/- 0.01 NN vs 1.45 +/- 0.03 OH (p < 0.01) vs 1.37 +/- 0.06 SH (p < 0.006)), consistent with an age-related reduction in diastolic filling. Heart rates were significantly higher in the hypertensive groups initially (63.5 NN vs 66.2 OH (p < 0.03) vs SH 67.3 (p < 0.01)) and increased in all groups over time, with the largest increase in the SH group (64.9 +/- 0.04 NN vs 67.8 +/- 1.02 OH (p < 0.0001) vs 70.9 +/- 1.6 SH (p < 0.01)). Stroke volume index changed in all groups over time, with the increase greatest in the NN group and least in the SH groups the reverse of this pattern was seen for changes in heart rate. All subjects gained weight over the 3 years of the study so that these unexpected changes in stroke volume index and heart rate could be a consequence of a weight gain-related increase in the sympathetic tone, although we have no direct evidence that this is the case. Should this be so, the smaller increase in stroke volume in conjunction with the larger increase in the heart rate in the sustained hypertensive group may reflect the effects of mild blood pressure elevation in producing a reduction in left ventricular diastolic function associated with a decrease in the inotropic responsiveness of the heart to enhanced sympathetic tone.

Adolescent↗

[The relation between EB virus and Burkitt's lymphoma].

OBJECTIVE: To study the relationship between Burkitt's lymphoma and Epstein-Barr (EB) virus. METHOD: Two cases of primary nasopharyngeal Burkitt's lymphoma in children were studies. Clinical features include nasal obstruction and dyspnea. The histology of Burkitt's lymphoma was confirmed by use of immunohistochemistry, in situ hybridization and double labelling techniques, the immunophenotype and EB virus locating sites were investigated. RESULTS: The EB positive cells are B cells and represent 60%-95% of the tumor cells. CONCLUSION: Nasopharyngeal primary Burkitt's lymphoma is associated with EB virus in Chinese.

Burkitt Lymphoma↗

[Finite element analysis of force produced by "T" loop retraction archwire].

This study introduced three presumed springs to imitate the three dimensional bolstering function of the bracket-tooth-periodontal tissue on the archwire with three dimensional finite element method (FEM), and, systematically analysed the force system produced by the "T" loop retraction archwire on the incisors. The following conclusions were drawn; (1) The activation of the "T" loop retraction archwire will produce extrusion and root lingual torque force as well as horizontal force on the incisors; (2) Adequate torqul on the incisor segment and gable bend mesial to the T-loop are necessary to control the position of the anterior teeth while they are being retracted; (3) retraction archwire should not be activated too much; (4) Lighter wire will produce milder and more durable forces.

Biomechanical Phenomena↗

[One-stage reimplantation for the salvage of total knee arthroplasty complicated by infection].

One-stage reimplantation for the salvage of infected total knee arthroplasty in 8 patients was reviewed at an average follow-up of 20.1 months late infections occurred in 7 (87.5%) patients. The timing of the diagnosis of the infection after knee arthroplasty was of the prosthesis averaged 11.5 months. No one had recurrent infection and pain was relieved significantly in all patients. Our results suggest that one-stage reimplantation is a reasonably reliable procedure for the management of an infected prosthesis. The use of Gentamicin-impregnated bone cement and the Streptomicin bead mixed with Gentamicin improve the success of treating or preventing recurrence of the infection. Early one-stage reimplantation was needed as soon as the deep infection was defined in order to decrease more destruction of the bone.

Adult↗

[Total knee replacement in diabetic patients].

From December 1987 to March 1995, 16 TKRs were performed for 9 diabetic patients at our department. 7 of them had rheumatoid arthritis (RA), and 2 osteoarthritis (OA). There were 1 male and 8 females. The average age was 55.9 years (range 49-69 years), and the average weight was 64.5 kg (range 54-78 kg). According to the hospital for special surgery (HSS) knee rating scale, the pre and postoperative evaluations were made. The HSS scores were improved after the operation from average 30.2 points preoperatively to 78.2 points postoperatively. The excellent and good rate was 94%. After 3.9 years follow-up (range 10 months to 8 years), the HSS score was 74.4 points, and the rate of excellent and good was 87.5%. Compared to the other 209 RA or OA patients with 287 TKR at the same period, the HSS score was almost the same, but the infection rate was higher (3.5%). We conclude that the TKR of diabetic patients could also get the similar results as common patients if the patients are under the good control of glycemia and medical treatment.

Aged↗

[Immunohistochemical study of hepatitis C virus core antigen and HBxAg in liver cirrhosis and hepatocellular carcinoma tissues].

OBJECTIVE: To study the distribution and significance of hepatitis C virus core antigen in liver cirrhosis and hepatocellular carcinoma tissues. METHODS: Hepatitis C virus antigen and HBx-Ag were detected in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) tissues with immunohistochemical methods. RESULTS: In some cases, not only was HCV core antigen positive stain distributed in the liver cells and nuclei of the cancer cell but it was also found in the cytoplasm. In different cases, it may be predominantly cytoplasm positive or nuclear positive or both. In liver cancer tissues, the HCV core antigen cytoplasmic positive cells were focally distributed and whereas the nuclear positive cells were diffusely distributed. The HCV core antigen nuclei positive cells were often observed in HCC tissues, but the cytoplasmic positive cells were often observed in the pericancerous liver tissue. The detection rates of HCV core antigen in LC, HCC and pericancerous liver tissues were 67.3% (66/98), 75.0% (78/104) and 48.1% (25/52), respectively. Statistical analysis suggested that: HCV core antigen nuclei positive rate in HCC be much higher than that in LC and pericancerous liver tissues (P < 0.01) and HCV core antigen nuclei positive rate be much higher than the cytoplasm positive rate in HCC tissues (P < 0.01). CONCLUSION: HCV, of which the infection being very common in LC and HCC of our country, may play an important role in the development of LC and HCC except HBV infection.

Carcinoma, Hepatocellular↗

[Comprehensive treatment of bone metastases of breast cancer: a clinical analysis of 70 cases].

OBJECTIVE: Bone metastasis is common in breast cancer patients and its main symptom is bone pain. A series of methods were tried to relieve bone pain and to improve quality of life. METHODS: 70 cases of bone metastases of breast cancer were divided into 2 groups and treated with either chemotherapy, radiotherapy, endocrine therapy or isotope therapy alone or in combination. RESULTS: Endocrine therapy or isotope therapy given alone was more responsive than chemotherapy or radiotherapy alone. When the treatment modalities were used comprehensively, the response rate was 90% as compared to 56.4% in patients given single modality treatment (P < 0.01). CONCLUSION: Endocrine or isotope therapy given alone is more effective than chemotherapy or radiotherapy alone. Patients positive for estrogen and progesterone receptors, are more suitable for endocrine therapy. Comprehensive treatment is recommended.

Adenocarcinoma↗

The effects of retinal ischemia on retinal nerve fiber layers of patients with retinal vein occlusion.

PURPOSE: To demonstrate the effects of retinal ischemia on retinal nerve fiber layer (RNFL) and the associated visual dysfunctions. METHODS: 52 subjects with retinal vein occlusion (RVO) were studied both in RVO eyes and in the contra-lateral eyes via red-free light fundus photography. The semi-quantitative analysis of RNFL defects was done, and the severity of RNFL defects of the ischemic and the non-ischemic groups were compared. RESULTS: The RNFL defects occurred in 75.5% of the total 53 eyes with RVO. The incidences of RNFL defects were significantly higher in eyes with cotton-wool spots and capillary non-perfusion than in other RVO eyes and controls. The RNFL defects were significantly severer in ischemic eyes than in non-ischemic ones. CONCLUSION: Retinal ischemia can result in RNFL defects, and the severity of RNFL defects was closely related to that of ischemia.

Adult↗

[The biological effects of recombinant human osteogenic protein-1 to cultured pulp cells].

The study was to observe the biological effects of rhOP-1 on the proliferation, ALPase activity and osteocalcin of dental pulp cells by cell culture technique, MTT, enzyme kinetic methods and radioimmunoassay. The results indicated rhOP-1 could obviously promote the proliferation and enhanced ALPase activity and osteocalcin secretion of pulp cells with showing dose-dependent relationship in this experimental dose range. Thus, rhOP-1 can induce dental pulp cells to differentiate the cells expressing osteoblast phenotype.

Alkaline Phosphatase↗