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Biomedical subjects

D Yu

Publications and source records attributed to D Yu.

At least 271 records · Page 15Linked to original sources
PubMed1992

Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer.

The c-erbB-2/neu gene encodes a transmembrane protein of 185 kDa (p185) with tyrosine kinase activity and extensive sequence homology to epidermal growth factor receptor. Amplification and overexpression of the c-erbB-2/neu gene has been shown in certain human tumors and is postulated to be important in human carcinogenesis. High levels of expression of the c-erbB-2/neu gene have been reported in non-small-cell lung cancer (NSCLC) cell lines and primary tumors from the United States. Since geographical and cultural factors may contribute to the development of certain types of cancer, we examined p185 examined p185 expression in 120 tumors from Chinese patients with lung cancers of different cell types and used immunohistochemical staining to determine the extent and general significance of p185 expression in human primary lung cancer. Our results demonstrate that 58.8% of the NSCLCs expressed p185 and that expression of p185 was observed only in NSCLC and not in small-cell lung cancers. Thirty-three of 41 adenocarcinomas and 24 of 55 squamous cell carcinomas among the NSCLCs examined were found to express p185 at levels different from those of normal lung. For the squamous cell carcinomas, p185 expression was correlated with lymph node metastasis (P less than 0.01), but for the adenocarcinomas, it was not (P greater than 0.05). In addition, expression of p185 in NSCLC was significantly more frequent in patients in advanced clinical stages. Our findings indicate that p185 expression is a frequent event and a general phenomenon in NSCLC and is correlated with poor clinical prognostic indicators, suggesting that expression of p185 may be of potential prognostic importance in NSCLC.

Adenocarcinoma↗
PubMed1992

The pathogenetic aspects of spondyloarthropathies from the point of view of HLA-B27.

The association of HLA-B27 and seronegative spondyloarthropathies, especially ankylosing spondylitis has been known for almost two decades. The spontaneous development of spondyloarthropathy like joint disease in HLA-B27 transgenic rats verifies the suspicion that the HLA-B27 antigens are directly responsible for disease development. With the recently revealed crystal structure of HLA-B27 and understanding of the class I molecule in general, a new hypothesis can be formulated based on the assumption that the pathogenesis of these diseases is a subversion of the physiological function.

Amino Acid Sequence↗
PubMed1992

Combined effects of laser irradiation and chemical inhibitors on the dissolution of dental enamel.

It has previously been shown that the susceptibility of human teeth to acid dissolution can be reduced by the presence of various chemical agents in the dissolution medium or by pretreatment of the teeth with laser irradiation. Now synergism between these two approaches to improving acid resistance has been demonstrated. Extracted human teeth were irradiated with a continuous-wave carbon dioxide laser at a wavelength of 10.6 microns. Energy doses of either 65 or 130 J/cm2 given over periods of 2 or 4 s, respectively, were applied and the teeth subjected to a severe acid challenge (0.1 M acetate buffer, pH 4.5, no calcium or phosphate common ion present) for 24 h. Mineral loss was assessed by measurement of mineral density profiles with quantitative microradiography. Experiments were carried out in the presence or absence of three chemical inhibitors with distinctly different mechanisms of action: ethane-1-hydroxy-1, 1-diphosphonic acid, fluoride, and dodecylamine HCl. Laser irradiation alone was found to lead to increased resistance of the teeth to acid challenge, with the higher energy dose being more effective than the lower dose. Each of the chemical inhibitors was effective on both lased and unlased teeth, with the percent reduction of dissolution greater when the inhibitors were applied to teeth lased with an energy dose of 130 J/cm2 which were already more resistant to acid challenge than were unlased teeth or teeth lased with a dose of 65 J/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

Initial dissolution rate studies on dental enamel after CO2 laser irradiation.

The influence of CO2 laser irradiation on the dissolution behavior of human dental enamel has been investigated. Human enamel was irradiated by a continuous-wave CO2 laser at 10.6 microns and initial dissolution rates (IDRs) were measured in 0.1 mol/L acetate buffer, pH = 4.5, both with and without calcium and/or phosphate common ion, by means of a rotating disk assembly. The effects of (1-hydroxyethylidene) bisphosphonic acid (EHDP), fluoride (F), and dodecylamine HCl (DAC) at various levels upon the IDR were also determined. All of the findings were consistent with the hypothesis that CO2 laser irradiation converts dental enamel to hydroxyapatite (HAP) possessing site #2 character (Yamamoto et al., 1986). The dissolution driving force function, KHAP = aCa10aPO4(6)aOH2, was found to have a value of 10(-129.9) after being lased, as compared with 10(-121.4) before being lased. The IDR values for EHDP (3 mmol/L) and DAC (3 mmol/L) were essentially zero as expected for site #2 HAP. For solution F, the deduced dissolution driving force function, KFAP = aCa10aPO4(6)aF2 was 10(-128.6) after being lased as compared with 10(-116.3) before being lased. These results all support the hypotheses (1) that laser irradiation may convert the surface of human dental enamel to an apatite of significantly lower effective solubility (i.e., site #2 HAP) than that of unlased enamel; and (2) that there is significant synergism between laser treatment and these chemical dissolution rate inhibitors (again consistent with site #2 HAP). Simple model calculations indicate that, in both the presence and absence of fluoride, these laser-induced changes in the driving force for dissolution should dramatically lessen the susceptibility of enamel to the types of acid challenge that might be encountered in the mouth.

Amines↗
PubMed1992

Effects of parathyroid hormone-related peptide on adenosine 3',5'-monophosphate and ornithine decarboxylase in a human colonic cell line.

PTH-related peptide (PTHrP) is widely distributed in normal tissues, including the gut, and is considered a potential autocrine or paracrine regulator of cellular growth and differentiation. With this in mind, a human colonic cell line (LoVo) was used to study the effect of PTHrP on ornithine decarboxylase (ODC), because ODC is known to have profound effects on the growth and differentiation of many cell types via stimulation of synthesis of polyamines. cAMP also was measured, because this second messenger has been implicated in the regulation of ODC activity. Nearly confluent LoVo cells, grown in F-12 medium and 10% fetal bovine serum (FBS), were preincubated in 1% FBS for at least 5 h, and then PTHrP-(1-34) was added, and the incubation was continued for up to 6 h. Cell extracts were analyzed for ODC activity by measuring 14CO2 liberated from 14C-labeled ornithine, for cAMP by RIA, and for ODC mRNA by Northern analysis. PTHrP produced dose-related increases in both cAMP (2- to 3-fold) and ODC (3- to 5-fold), with a maximal effect at 0.1-1 microM and an ED50 of 1-10 nM. Comparison of the cAMP and ODC responses to PTHrP showed a strong correlation (r = 0.96; P less than 0.001). The effects of 1 microM PTHrP-(1-34) to increase cAMP and ODC were completely inhibited by 10-20 microM of the specific antagonist [Asn10,Leu11]PTHrP-(7-34). PTHrP-(1-34) did not stimulate ODC activity when cells were incubated without FBS. The stimulation of ODC activity by PTHrP-(1-34) was maximal at 2 h, a time at which an increase in ODC mRNA also was evident. PTH-(1-34) and forskolin also stimulated ODC activity, but PTHrP-(67-86) amide was ineffective. The results indicate that the N-terminal portion of the PTHrP molecule can stimulate ODC activity in a human colon cell line and that the effect is probably mediated by cAMP. The results are consistent with the idea that PTHrP may influence cell growth and differentiation in the gut via an effect on polyamine biosynthesis. Since LoVo cells also express PTHrP mRNA, this gastrointestinal cell line may serve as a useful model for studying autocrine regulation of gut cell growth and differentiation by PTHrP.

Cell Line↗
PubMed1992

Effects of vasoactive intestinal peptide on adenosine 3',5'-monophosphate, ornithine decarboxylase, and cell growth in a human colon cell line.

Vasoactive intestinal peptide (VIP) is a widely distributed neuropeptide that has been considered a potential regulator of cell growth and differentiation in various tissues, including the gut. To examine this idea, we used a human colon carcinoma cell line (LoVo) as a model system and measured ornithine decarboxylase (ODC), because this is the rate-limiting enzyme for the formation of polyamines, which are thought to be key factors in regulating cell growth. LoVo cells, grown to about 80% confluence in F-12 medium containing 10% fetal bovine serum, were preincubated for 5 h in low serum medium (1% fetal bovine serum in F-12), and ODC activity was determined by measuring 14CO2 liberated from 14C-labeled ornithine. VIP caused a dose-related biphasic change in ODC, with activity increased at 10 pM, maximal (5-fold increase) at 10 nM, and decreased toward basal at 100 nM to 1 microM. Incubation of cells for 6 days with VIP in low serum medium showed similar changes in cell numbers, with growth being increased by doses in the 1 pM to 100 nM range and decreased at higher doses (greater than or equal to 100 nM). Exposure of cells to 5 mM alpha-difluoromethylornithine blocked both the VIP-induced increase in cell number and the VIP-induced increase in ODC activity. Increased ODC mRNA was detected after 2 h of exposure to VIP, a time at which ODC activity peaked after treatment, and the increase in ODC mRNA caused by VIP was dose-dependent. In related experiments LoVo cells were found to have high affinity VIP receptors (Kd = 0.4 nM), as assessed by examination of [125I]VIP binding in the presence of varying concentrations of unlabeled VIP. Studies of intracellular cAMP revealed a dose-related increase in cAMP in response to VIP (ED50 = 11 pM), and the adenylate cyclase activator forskolin increased both ODC activity and ODC mRNA. The findings support the idea that LoVo cells have VIP receptors linked to cAMP which can stimulate cell growth at least in part by increasing ODC synthesis and activity, thereby altering the production of polyamines. The decreased growth and ODC activity observed with high doses of VIP may involve a second messenger other than cAMP.

Adenocarcinoma↗
PubMed1992

[The correlation between clozapine saliva level and clinical response as well as side effect in patient with schizophrenia].

It was measured for clozapine saliva level in 62 patients with schizophrenia taking clozapine, the study have found that therapeutic window was at the range from 550 ng/ml to 920 ng/ml in 34 patients with duration more than two years and was at the range from 400 ng/ml to 510 ng/ml in 28 patients with duration less than two years. Clozapine saliva concentration has positively correlated with improvement of though disorders and hostility & suspiciousness in 30 patients with duration more than two years and with improvement of activation in 12 patients with duration less than two years and with anti-adrenergic side effect in 62 patients, the latter effect was significant increased when clozapine saliva level was more than 380 ng/ml.

Adolescent↗
PubMed1992

Mechanisms of c-erbB2/neu oncogene-induced metastasis and repression of metastatic properties by adenovirus 5 E1A gene products.

c-erbB2/neu is a transforming oncogene that encodes a 185-kDa transmembrane glycoprotein. In many but not all studies, amplification and/or overexpression of the human c-erbB2/neu oncogene has been correlated with poor prognosis and the number of lymph node metastases in node-positive breast cancer patients. We have shown that expression of the activated rat c-erbB2/neu oncogene in mouse embryo fibroblast 3T3 cells is sufficient to induce experimental metastases in nude mice. Important steps in the metastatic event are tumor cell adhesion to endothelial cells and invasion of basement membranes. Therefore, we further examined the ability of c-erbB2/neu oncogene-transformed 3T3 cells to adhere to microvessel endothelial cells and secrete basement membrane-degradative enzymes. The c-erbB2/neu oncogene-transformed 3T3 cells were shown to be more adherent and have higher gelatinase activities. Since we had previously shown that the adenovirus 5 E1A gene product can suppress c-erbB2/neu-induced transformation of 3T3 cells, we examined the possibility that E1A can abrogate the metastatic properties of c-erbB2/neu-transformed 3T3 cells. We found that introduction of the E1A gene into c-erbB2/neu-transformed 3T3 cells reduced the formation of experimental metastatic tumors and inhibited metastasis-associated properties, such as adhesion to microvessel endothelial cells, migration through a layer of reconstituted basement membrane (Matrigel) and secretion of basement membrane-degradative enzymes. The results indicate that the mechanism by which the c-erbB2/neu gene induces higher metastatic potential is to promote adhesion and invasion steps of the metastatic cascade. The E1A gene, which functions by inhibiting these steps, is thus a suppressor gene for c-erbB2/neu-induced experimental metastasis.

Adenovirus E1A Proteins↗
PubMed1991

One-step isolation of alpha 1-acid glycoprotein.

alpha 1-Acid glycoprotein could be isolated by a one-step extraction method from human sera and plasma. Protein recovered in the water phase after extraction with phenol at 70 degrees C for 20 min was verified as human alpha 1-acid glycoprotein when it was compared with the reference standard human alpha 1-acid glycoprotein by Ouchterlony double immunodiffusion, sodium dodecylsulfate-polyacrylamide gel electrophoresis, Western blot analysis, and periodic acid-Schiff stain. The present isolation procedure is simple and fast, and can extract about 81% of the total alpha 1-acid glycoprotein in the sera and plasma, as determined by radial immunodiffusion.

Blotting, Western↗
PubMed1991

Infectious agents and other nongenetic immunologic factors in spondyloarthropathies.

Because one of the spondyloarthropathies, reactive arthritis, is induced by infections, research into the role of arthritis-causing bacteria has been strongly emphasized. The most remarkable finding in recent years is the detection of some of the bacterial components in the articular compartment, in some cases even several years after the development of arthritis. This location would account for the fact that T lymphocytes in the synovial compartment demonstrate a high in vitro response to preparations of the arthritis-causing bacteria. The persistence of these bacterial components would explain the frequently reported prolonged antibacterial antibody response in arthritis patients. Although the factors leading to the location and persistence of the bacteria are not clear, the finding provides a rationale for treating these patients with long-term antibiotics. A major question being investigated is how the presence of bacterial components in the articular compartment is related to the predominance of HLA-B27 in many of the patients.

Animals↗
PubMed1991

Hydroxyapatite cement based drug delivery systems: drug release in vitro.

A novel approach using a self-setting hydroxyapatite (HAP) cement as a skeletal drug delivery system has been proposed to solve the problem of delivering drugs to skeletal tissue at high local concentrations for desirable therapeutic effects. Hydroxyapatite cements loaded with antibiotics can be formed in situ and can be used as bonding materials between bone and prostheses as well as for drug release devices. The cement also possesses sufficient mechanical strength to be a potential bone grafting material. Using cephalexin and norfloxacin as model drugs, the continuous in vitro release profiles of these compounds from 0.9-4.8% by weight loaded cement pellets were observed. These drug release patterns correlated well with the Higuchi model. This hydroxyapatite cement drug delivery system can be applied in the treatment of osteomyelitis and infected compound fractures.

Bone Cements↗
PubMed1990

Transcriptional repression of the neu protooncogene by the adenovirus 5 E1A gene products.

Amplification/overexpression of the human neu protooncogene has been frequently found in human primary breast and ovarian cancers and is correlated with the number of axillary lymph nodes positive for metastasis in breast cancer patients. Identification of the factors controlling transcription of the neu gene is essential for understanding the mechanisms of neu gene regulation and its role in tumorigenicity. The adenovirus early region 1A (E1A) gene products are pleiotropic transcription regulators of viral and cellular genes and have been identified as a viral suppressor gene for metastasis. Here we demonstrate that transcription of neu can be strongly repressed by the E1A gene products. The 13S and 12S products of E1A gene are effective at repressing neu transcription and the transcriptional repression requires the conserved region 2 of the E1A proteins. The target for E1A repression was localized within a 139-base-pair DNA fragment in the upstream region of the neu promoter. In addition, competition experiments suggest that the sequence TGGAATG, within the 139-base-pair fragment, is an important element for the E1A-induced repression. These results indicate that E1A negatively regulates neu gene expression at the transcriptional level by means of a specific DNA element.

Adenovirus Early Proteins↗
PubMed1990

A novel skeletal drug delivery system for anti-bacterial drugs using self-setting hydroxyapatite cement.

To solve the problem of delivering drugs to skeletal tissue at high enough local concentrations for desirable therapeutic effects, we report a novel approach using a self-setting hydroxyapatite cement, with cephalexin and norfloxacin as model drugs. After setting, the cement was transformed into hydroxyapatite with affinity for hard bone tissue. Continuous in-vitro drug release profiles from loaded cement pellets (0.9-4.8% by weight) in phosphate buffer at pH 7.4 and 37 degrees C followed the Higuchi equation.

Anti-Infective Agents↗
PubMed1990

[Erythrocyte deformability and extracorporeal thrombosis in patients with blood stasis syndrome].

The patients were divided into 3 groups: 127 cases of cor pulmonale, 47 cases of glomerulonephritis and 17 cases of coronary heart disease. Erythrocyte deformability indices (DI) and changes during extracorporeal thrombosis were investigated in all the 3 groups, in comparison with a group of 80 normal healthy individuals. The result showed that all the patients had notably lower DI (respectively 1.21 +/- 0.99, 0.73 +/- 0.93), and 0.84 +/- 0.81 for the groups in the given order), longer length of extracorporeal thrombi (L in mm, respectively 45.94 +/- 38.78, 62.88 +/- 43.65 and 59.74 +/- 40.99) and larger top inclination angle of blood plane in silicon-lined ring tube (respectively 15.66 degrees +/- 6.09 degrees, 13.21 degrees +/- 9.33 degrees and 12.65 degrees +/- 8.02 degrees) than individuals over 40 in the comparison group. In the group of cases of cor pulmonale, patients with abnormal pH and respiratory failure had apparent greater L than those with pH compensation and without respiratory failure; diminished DI were also observed in association with pH abnormality. In the group of nephritis, patients with renal failure and chronic nephritis showed evidently lower DI than those without renal failure but acute nephritis; increased L were also noted in association with renal failure. In addition, a similar comparison was done between individuals over 40 and individuals at or younger than the age of 40. It was found that people over 40 tended to have diminished DI, increased L and Wt of extracorporeal thrombi, and augmented initial inclination angle of blood plane though not as notably as what was observed in the 3 groups of victims of blood stasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

No influence of enzyme inhibitors on the hydroxylation of methotrexate in rats.

In anaesthetized rats 50% of an infused dose of methotrexate (MTX) was excreted into the bile. About 3% was metabolized to 7-hydroxymethotrexate (7-OH-MTX), which appeared also in the bile. Pretreatment with allopurinol had no influence on the elimination of MTX or the production of 7-OH-MTX during a 3-h infusion of MTX. Cyanamide decreased the total MTX clearance, but increased the biliary elimination of 7-OH-MTX. Phorone decreased the biliary MTX-clearance, but not the biliary secretion of 7-OH-MTX. The results show that neither aldehyde oxidase nor xanthine oxidase is the predominant hydroxylating enzyme for MTX in the rat.

Aldehyde Oxidase↗