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Y Lu

Publications and source records attributed to Y Lu.

At least 757 records · Page 42Linked to original sources
PubMed1995

Phosphatidylinositol 3-kinase activity is not essential for CD28 costimulatory activity in Jurkat T cells: studies with a selective inhibitor, wortmannin.

The interaction of CD28 with its counter-receptor, B7-1 (CD 80), on antigen-presenting cells induces a co-signal in T cells required to promote antigen-dependent interleukin-2 (IL-2) production and to prevent clonal anergy. CD28 stimulation causes both protein-tyrosine kinase and phosphatidylinositol3-kinase (PI3-K) activation, suggesting a possible role for these enzyme activities in CD28 co-signal transduction. Here, we investigate the effect of wortmannin, a selective and irreversible PI3-K inhibitor on CD28 co-signaling events in the Jurkat T cell line. Wortmannin added to cell cultures partially inhibits CD28-induced tyrosine phosphorylation of the putative p110 catalytic subunit of PI3-K, but does not block CD28-induced association of the p85 PI3-K regulatory subunit with the CD28 receptor. Wortmannin inhibits in a dose-dependent manner both total cellular PI3-K activity and CD28-induced receptor-associated PI3-K activity. Wortmannin (1 microM) inhibits cellular PI3-K activity by 90% with complete inhibition achieved at 10 microM. The inhibitory effect of wortmannin on cellular PI3-K activity is prolonged ( > 18 h), suggesting that the drug is not readily metabolized by Jurkat T cells. Wortmannin, at concentrations that blocked PI3-K activity, fails to inhibit the synergistic effect of CD28 on IL-2 secretion in the presence of phorbol 12-myristate 13-acetate and ionomycin. These data demonstrate that CD28-induced signaling events other than the activation of PI3-K catalytic activity contribute to the control of IL-2 secretion.

Androstadienes↗
PubMed1995

3D laser scanning for image guided stereotactic neurosurgery.

While this work is in its very early stages, the 3D laser scanner shows significant promise as a surgical localization device with advantages over other sensing methods. Accurate 3D surface extraction and matching, a central problem in computer vision, is the key to frameless stereotaxic neurosurgery using this technique.

Brain↗
PubMed1995

Influence of degenerative joint disease on spinal bone mineral measurements in postmenopausal women.

We assessed the impact of various forms of spinal degenerative joint disease (DJD) on bone mineral density (BMD) measured by quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) in a group of postmenopausal women. Lateral (T4-L4) and AP (L1-L4) spinal radiographs were reviewed for fracture and DJD in 209 women (mean age 62.6 +/- 6.7). The severity of DJD findings was graded as 0, 1, or 2 on the lumbar films, except for vertebral osteophytes which were graded from 0 to 3. Vertebral fractures were defined semiquantitatively as approximately 20% reduction in anterior, middle, or posterior vertebral height. BMD was measured in all subjects by QCT and DXA, including posteroanterior DXA (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). When BMD was measured by QCT and mL-DXA in the 168 women without fractures, no significant differences were found between women with and those without DJD. However, BMD by PA-DXA was significantly higher in women with DJD changes, particularly when osteophytes were present at the vertebral bodies or facet joints. BMD by L-DXA was less affected by DJD. For this measurement a significant increase in BMD was only noted in subjects with vertebral osteophytes. Multivariate analysis of variance (MANOVA) showed that BMD by QCT and mL-DXA was not affected by DJD. In contrast, for all women, BMD by PA- and L-DXA was affected more by DJD than by fracture status. Chi-square testing demonstrated no significant relationships between vertebral fractures and any of the DJD changes. We conclude that QCT and mL-DXA are superior to PA-DXA and L-DXA in detecting bone loss in patients with DJD. Thus, for these patients, BMD assessment by QCT or mL-DXA may be advisable.

Absorptiometry, Photon↗
PubMed1995

Spinal bone mineral assessment in postmenopausal women: a comparison between dual X-ray absorptiometry and quantitative computed tomography.

We compared quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) with respect to their ability to discriminate subjects with and without prevalent vertebral fractures. In 240 post-menopausal women (mean age 63.7 +/- 6.9 years) lateral spine radiographs (T4-L4) were reviewed for the presence of vertebral fracture. Using a semiquantitative technique to grade the severity of vertebral deformities, we classified fractures as mild, moderate or severe (grade 1 to 3, respectively). Postero-anterior DXA (PA-DXA) and lateral DXA (L-DXA) measurements (L2-4) as well as QCT measurements of the lumbar spine (T12-L3 or L1-14) were obtained in all women. Seventy-two women were diagnosed with at least one fracture, and of these 40 were graded as mild. Comparing normal women with fractured women, we found the area under the receiver operating characteristics (ROC) curves to be greatest for QCT (0.81), followed by L-DXA (0.72) and PA-DXA (0.65). The differences among all three techniques were significant. Comparing the normal women with women having only mild fractures, the areas under the ROC curves were 0.79, 0.73 and 0.63 for QCT, L-DXA and PA-DXA, respectively. Significant differences existed between QCT and PA-DXA as well as between L-DXA and PA-DXA. Logistic regression analysis also revealed the highest age-adjusted odds ratios for QCT (3.67; 2.25-5.97) while L-DXA and PA-DXA showed substantially lower odds ratios (2.00; 1.39-2.87, and 1.54; 1.11-2.15, respectively). We conclude that low bone density as measured by QCT, PA-DXA or L-DXA is significantly associated with the prevalence of vertebral fractures. Of the methods studied, QCT of trabecular bone offered the best discriminatory capability. L-DXA proved to be superior to PA-DXA in its diagnostic sensitivity, particularly in women with mild fracture. Mild vertebral fractures are associated with decreased spinal bone density and may be regarded as osteoporotic deformities.

Absorptiometry, Photon↗
PubMed1995

Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques.

Assessment of precision errors in bone mineral densitometry is important for characterization of a technique's ability to detect longitudinal skeletal changes. Short-term and long-term precision errors should be calculated as root-mean-square (RMS) averages of standard deviations of repeated measurements (SD) and standard errors of the estimate of changes in bone density with time (SEE), respectively. Inadequate adjustment for degrees of freedom and use of arithmetic means instead of RMS averages may cause underestimation of true imprecision by up to 41% and 25% (for duplicate measurements), respectively. Calculation of confidence intervals of precision errors based on the number of repeated measurements and the number of subjects assessed serves to characterize limitations of precision error assessments. Provided that precision error are comparable across subjects, examinations with a total of 27 degrees of freedom result in an upper 90% confidence limit of +30% of the mean precision error, a level considered sufficient for characterizing technique imprecision. We recommend three (or four) repeated measurements per individual in a subject group of at least 14 individuals to characterize short-term (or long-term) precision of a technique.

Absorptiometry, Photon↗
PubMed1995

Glutathione disulphide as a marker of reperfusion injury in ischaemic skin flaps.

Estimation of the oxidised form of glutathione (GSSG) in an ischaemic/reperfused organ is frequently employed as an indicator of oxidative stress created by the production of oxygen free radicals during the reperfusion period. The time course of oxidative stress and tissue damage in 19 ischaemic/reperfused guinea-pig island skin flaps was evaluated. No-flow ischaemia was induced in the flaps for 6 h in 7 animals, and for 8 h in 9 animals (a further 3 animals served as controls without ischaemia). Arterial and venous blood samples were obtained directly from the flap pedicle at baseline, 10, 30, and 60 min following reperfusion. Results suggest that a second focus of oxidative injury, possibly mediated by activated neutrophils, contributes to the overall process of reperfusion injury. Plasma levels of GSSG allow for a more sensitive quantification of oxidant stress within reperfused ischaemic flaps, and may serve as a useful tool in skin flap research.

Animals↗
PubMed1995

Development of a quantal assay in primary shrimp cell culture for yellow head baculovirus (YBV) of penaeid shrimp.

A 50% tissue culture infectious dose assay (TCID50) using primary culture of shrimp lymphoid organ (Oka) cells was developed for the quantitative titration of yellow-head baculovirus (YBV), a newly isolated virus of penaeid shrimp. The assay protocol includes the use of Primaria-grade 96-well tissue culture plates to grow the primary lymphoid organ cells of penaeid shrimp. A 15% gill suspension from YBV-infected shrimp was determined to have an infectious virus titer of 5 x 10(5.75) TCID50/ml. This report represents the first convenient assay protocol using cell culture derived from penaeid shrimp to titer a shrimp virus.

Animals↗
PubMed1995

Elevated IgE level in relationship to nutritional status and immune parameters in early human immunodeficiency virus-1 disease.

Elevation of IgE has been associated with T-cell dysregulation and with the occurrence of opportunistic infections in patients with acquired immunodeficiency syndrome. The precise cause of IgE overproduction during the early stages of human immunodeficiency virus (HIV)-1 disease, however, has not been established. In light of reports demonstrating that IgE production may be affected by vitamin E levels in an animal model, we evaluated nutritional status in relationship to plasma IgE levels and immune parameters in 100 asymptomatic HIV-1-seropositive and 42 HIV-1-seronegative homosexual men. Approximately 18% of the HIV-1-seropositive population demonstrated biochemical evidence of plasma vitamin E deficiency (< 5 micrograms/ml). Subsequent analysis of available samples indicated a dramatic elevation of IgE levels (308 +/- 112 IU/ml) in vitamin E-deficient seropositive subjects (n = 9) as compared with age and CD4-matched HIV-1-seropositive persons with adequate vitamin E levels (n = 16, 118.1 +/- 41.1 IU/ml) and significantly lower levels (59.5 +/- 15.7 IU/ml) in HIV-1-seronegative men (n = 20, p = 0.01). This effect, which was independent of CD4 cell count, did not appear to be influenced by atopic or gastrointestinal parasitic disease. The low plasma vitamin E levels were related at least in part to dietary intake (r = 0.552, p = 0.01), suggesting that supplementation may be warranted in HIV-1-infected persons in whom vitamin E deficiency develops. Analysis of covariance revealed a strong relationship between IgE levels and CD8 cell counts (p < 0.006), and between IgE level and vitamin E deficiency (p < 0.039).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome.

Sensitivity of blood pressure to dietary salt is a common feature in subjects with hypertension. These features are exemplified by the mendelian disorder, Liddle's syndrome, previously shown to arise from constitutive activation of the renal epithelial sodium channel due to mutation in the beta subunit of this channel. We now demonstrate that this disease can also result from a mutation truncating the carboxy terminus of the gamma subunit of this channel; this truncated subunit also activates channel activity. These findings demonstrate genetic heterogeneity of Liddle's syndrome, indicate independent roles of beta and gamma subunits in the negative regulation of channel activity, and identify a new gene in which mutation causes a salt-sensitive form of human hypertension.

Adolescent↗
PubMed1995

Identification of an endogenous inhibitor of prostatic carcinoma cell growth.

The rate of expansion of primary prostatic carcinoma is comparatively slow, with tumours frequently taking years or decades to reach clinically relevant size. We now report the presence of an endogenous inhibitor, derived from aqueous extracts of human prostate tissue, which blocks prostatic carcinoma cell proliferation in vitro and prevents subcutaneous tumour expansion in vivo. Purification and characterization revealed the inhibitor to be spermine, a polyamine known to be locally abundant in the prostate. These results suggest that endogenous polyamine can negatively regulate the growth of prostatic carcinoma cells at their primary site in vivo and may explain the slow rate of primary tumour expansion in the prostate.

Adenocarcinoma↗
PubMed1995

Prolonged induction of p21Cip1/WAF1/CDK2/PCNA complex by epidermal growth factor receptor activation mediates ligand-induced A431 cell growth inhibition.

Proliferation of some cultured human tumor cell lines bearing high numbers of epidermal growth factor (EGF) receptors is paradoxically inhibited by EGF in nanomolar concentrations. In the present study, we have investigated the biochemical mechanism of growth inhibition in A431 human squamous carcinoma cells exposed to exogenous EGF. In parallel, we studied a selected subpopulation, A431-F, which is resistant to EGF-mediated growth inhibition. We observed a marked reduction in cyclin-dependent kinase-2 (CDK2) activity when A431 and A431-F cells were cultured with 20 nM EGF for 4 h. After further continuous exposure of A431 cells to EGF, the CDK2 activity remained at a low level and was accompanied by persistent G1 arrest. In contrast, the early reduced CDK2 activity and G1 accumulation in A431-F cells was only transient. We found that, at early time points (4-8 h), EGF induces p21Cip1/WAF1 mRNA and protein expression in both EGF-sensitive A431 cells and EGF-resistant A431-F cells. But only in A431 cells, was p21Cip1/WAF1 expression sustained at a significantly increased level for up to 5 d after addition of EGF. Induction of p21Cip1/WAF1 by EGF could be inhibited by a specific EGF receptor tyrosine kinase inhibitor, tyrphostin AG1478, suggesting that p21Cip1/WAF1 induction was a consequence of receptor tyrosine kinase activation by EGF. We also demonstrated that the increased p21Cip1/WAF1 was associated with both CDK2 and proliferating cell nuclear antigen (PCNA). Taken together, our results demonstrate that p21Cip1/WAF1 is an important mediator of EGF-induced G1 arrest and growth inhibition in A431 cells.

CDC2-CDC28 Kinases↗
PubMed1995

Micronutrients and HIV-1 disease progression.

OBJECTIVE: To determine whether nutritional status affects immunological markers of HIV-1 disease progression. DESIGN: A longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. METHODS: Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. RESULTS: Development of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P = 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by zidovudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P = 0.041) and the AIDS index (P = 0.005). CONCLUSIONS: These data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Adult↗
PubMed1995

Amplification and expression of the c-erbB-2 oncogene in normal, hyperplastic, and malignant endometria.

Using differential polymerase chain reaction (DPCR), dot blot hybridization, and an immunohistochemical technique, we determined the amplification and expression of the c-erbB-2 oncogene in 25 normal, 31 hyperplastic, and 72 malignant samples of the endometrium in 128 patients. Using DPCR, we found amplified c-erbB-2 (two to 12 copies) in two of 25 (8%) normal, 15 of 31 (48%) hyperplastic, and 45 of 72 (63%) malignant samples. These results were closely correlated with those from dot blot (r = 0.78). When comparing the results of DPCR with those of the immunohistochemical method, we noted that the negative findings coincided with one another, i.e., nonamplification was associated with the absence of immunoreactivity. Further analysis showed that amplified c-erbB-2 was found significantly more in complex and atypical hyperplasias versus simple hyperplasias. This indicates that c-erbB-2 may play a potential role in the early development of some endometrial carcinomas. Although no correlation was seen between c-erbB-2 amplification and overall survival in our patients, high-level c-erbB-2 amplification (at least five copies) was significantly associated with the histological grade of endometrial carcinoma and vascular or lymphatic invasion. It is possible that high-level c-erbB-2 amplification identifies a subset of aggressive endometrial carcinoma that involves vascular or lymphatic invasiveness and poor cell differentiation.

Base Sequence↗
PubMed1995

Immunoglobulin E levels in relationship to HIV-1 disease, route of infection, and vitamin E status.

Our recent studies have demonstrated that in early HIV-1 infection, elevation of plasma immunoglobulin E (IgE) levels precedes the decline of CD4 cell count and is influenced by vitamin E status. In order to further investigate the role of IgE elevation in HIV-1 infection, we determined IgE levels in HIV-1-seropositive and -seronegative intravenous drug users (IDUs) (n = 38), in relationship to cellular and humoral immune function, liver enzymes, and vitamin E status. To examine the possible impact of the route of HIV-1 infection on IgE levels, comparisons between the cohorts of the HIV-1-seropositive and -seronegative IDUs and homosexual men (n = 45) were also conducted. All HIV-1-seropositive participants had significantly higher (P = 0.003) IgE levels than the HIV-1-seronegative subjects. The HIV-1-seropositive IDUs, moreover, demonstrated significantly higher (P = 0.01) IgE levels than HIV-1-seropositive homosexual men, despite similar CD4 cell counts. Stepwise regression analysis was used to evaluate the possible variables contributing to the IgE variation. HIV-1 status (P = 0.0009), intravenous drug use (P = 0.014), CD8 cell counts (P = 0.0001), plasma level of vitamin E (P = 0.006), and alcohol intake (P = 0.047) were significant, accounting for 71% of the IgE elevation. These findings suggest that IgE may serve as a sensitive marker to reflect the evolution of HIV-1 disease in individuals from different risk groups.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Dose-surface histograms as treatment planning tool for prostate conformal therapy.

Dose-surface histograms are studied and compared with dose-volume histograms, as an evaluation tool for prostate treatment planning. For thin walled hollow organs, such as the rectum and bladder, the surface area irradiated is a more appropriate measure of the biological effect than the full volume. It is also more accurate and efficient to define the surface for a hollow structure and compute the surface area histograms. Application of the dose-surface histograms provide new insights into prostate treatment planning. A simple idealized geometry model demonstrates that the percentage surface area intersected by the geometric beam edge differs from the percentage volume intersected. For a group of prostate patients, it is shown that the dose-surface histograms yield substantially different results from the dose-volume histograms in ranking four-, six-, and, eight-field treatment plans and in calculating the fraction of the rectum irradiated to high dose. The difference in terms of surface area between these plans in the high-dose region is usually less than that in terms of the volume, and a reverse of plan ranking order can consequently occur. The percentage of organ surface irradiated to high dose is typically greater than the percentage volume by 5% to 10%. The use of the dose-surface histograms in analysis of organ motion and/or patient setup uncertainty, and analysis of rectal complications, is also discussed.

Biophysical Phenomena↗