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Biomedical subjects

Y Lu

Publications and source records attributed to Y Lu.

At least 613 records · Page 34Linked to original sources
PubMed1997

A fraction unresponsive to growth inhibition by TGF-beta among the high-proliferative potential progenitor cells in bone marrow of p53-deficient mice.

Transforming growth factor-beta (TGF-beta) has been found to block the progression of the cell-cycle by up-regulating a Cdk inhibitor, p15, only in epithelial cells; on the other hand, wild-type p53 was shown to activate transcriptionally the gene for another Cdk inhibitor, p21. The regulatory effects of TGF-beta on hematopoietic tissues is poorly understood. Hence, we investigated the effect of TGF-beta on hematopoietic progenitor cells in p53-deficient mice to determine whether an inhibitory signal from TGF-beta is linked to p53 in hematopoietic regulation. We found that the proliferation of megakaryocyte-progenitors (CFU-Mk) in our wild-type mice was markedly inhibited by TGF-beta. Contrary to an earlier report, an erythroid and a granulocyte-macrophage progenitor, stimulated by IL-3, were not significantly inhibited, whereas TGF-beta also completely inhibited the growth of high-proliferative potential progenitor cells (HPP-CFC) in the marrow of mice with 5-fluorouracil (5FU), as reported. It is interesting that in the p53-deficient mice, the inhibitory action of TGF-beta on the HPP-CFC was incompletely abolished. The response curve we obtained for graded doses of TGF-beta suggests that there is, at least, a subpopulation of HPP-CFC which is less sensitive to the regulation by TGF-beta. In contrast to HPP-CFC, the CFU-Mk, which TGF-beta inhibited only in wild-type mice not treated with 5FU, remained inhibited in the p53-deficient strain. Thus, HPP-CFC might be regulated by TGF-beta through their signal pathways which are linked to p53.

Animals↗
PubMed1997

Functional dose-volume histograms for functionally heterogeneous normal organs.

Functional dose-volume histograms are proposed as an extension of the conventional dose-volume histograms, for quantitative assessment of three-dimensional radiation dose coverage of functionally heterogeneous normal organs. Examples are given to illustrate possible applications of this approach to the treatment of a brain tumour or a lung tumour, in which cases the distribution of the normal organ function can be obtained from functional dose-volume modalities. It is shown that a significant difference exists between the functional dose-volume histograms and the conventional dose-volume histograms when the normal organ function is non-uniformly distributed within the organ. Utilization of functional dose-volume histograms as the input for the calculation of normal tissue complication probabilities is discussed for different normal tissue structures.

Humans↗
PubMed1997

Sulbactam/cefoperazone versus cefotaxime for the treatment of moderate-to-severe bacterial infections: results of a randomized, controlled clinical trial.

We conducted a randomized, open-label, controlled, multicenter study to compare sulbactam/cefoperazone with cefotaxime in terms of efficacy and safety for the treatment of hospitalized patients with moderate-to-severe bacterial infections. More than two-thirds of the pathogens recovered from these patients produced beta-lactamase. Two hundred-seven (88.1%) of the 235 patients enrolled completed the study and were included in the efficacy and safety evaluations. One hundred-three patients received sulbactam/cefoperazone (2-4 g/d) administered in evenly divided doses every 12 hours by a 30-minute intravenous drip; 104 patients received cefotaxime (6-12 g/d) administered in evenly divided doses every 6 or 8 hours by a 30-minute intravenous drip. The overall efficacy rates (i.e., cure or markedly improved) were 95% for the sulbactam/cefoperazone group and 90% for the cefotaxime group (P = .186), whereas the bacterial eradication rates were 85% for the sulbactam/cefoperazone group and 81% for the cefotaxime group (P = .467). Both drug regimens were well tolerated. Sulbactam/cefoperazone is effective and safe for the treatment of moderate-to-severe bacterial infections caused mainly by beta-lactamase-producing organisms.

Adolescent↗
PubMed1997

Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in porcine endotoxic shock.

OBJECTIVE: To determine the effects of the stable prostacyclin analog, iloprost, in a porcine model of endotoxin-induced mesenteric ischemia. DESIGN: Prospective, experimental, randomized, controlled study. SETTING: Animal research laboratory at a university medical center. INTERVENTIONS: Pigs were randomized to receive a constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of carrier solution (normal saline) 30 mins before being infused with endotoxin (100 microg/kg over 1 hr). The infusion with iloprost or carrier solution was continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS: Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy during which a magnetic flowprobe was placed around the superior mesenteric artery and an ileal tonometer was inserted. Thirty minutes before they were infused with endotoxin, the animals were randomized to receive intravenous iloprost or normal saline. Endotoxin was infused centrally over a 60-min period. Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the start of the endotoxin infusion. Data were measured at the end of the endotoxin infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by the dosage of iloprost used in this experiment. After resuscitation, the cardiac output returned to baseline in the iloprost-treated group but remained decreased in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric blood flow increased 34% above baseline levels in animals pretreated with iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7 kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44 +/- .23) in the control group than in the iloprost-treated group. CONCLUSIONS: Pretreatment with intravenous iloprost effectively increased intestinal blood flow in this model of endotoxin-induced mesenteric ischemia. This action of the drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose iloprost had no effect on mean arterial pressure, it may be a useful adjunct in the treatment of sepsis and septic shock.

Acidosis↗
PubMed1997

Soluble E-selectin and intercellular adhesion molecule-1 plasma levels increase during acute myocardial infarction.

Previous studies have shown that adhesion molecules play a crucial role in leukocyte-endothelium interactions that occur during myocardial ischemia and reperfusion. We assessed the plasma levels of the soluble form of E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) in 15 patients with acute myocardial infarction (AMI) and in 15 controls with chronic stable angina. In patients with AMI, the levels of sE-selectin and sICAM-1 increased significantly during the first 8 h after infarction and subsequently decreased. Soluble E-selectin levels were inversely related to the peak plasma levels of creatine kinase-MB (CK-MB), and the time course of their appearance in plasma correlated with that of neutrophil count and plasma D-dimer. In individual patients, peak and mean sICAM-1 levels correlated respectively with plasma D-dimer concentrations and monocyte count, but no correlation were found when their time courses were analyzed. Eight hours after symptom onset, the mean plasma sE-selectin levels were higher in patients with AMI than in those with stable angina, whereas no significant differences were found in mean plasma sICAM-1 levels between the two groups at every time analyzed. In the acute phase of MI (a) sE-selectin and sICAM-1 levels increase during the first 8 h and subsequently decrease; (b) the increase in sE-selectin probably reflects activation of endothelial cells, correlates with other inflammatory and coagulation parameters, and is inversely related to the degree of myocardial damage; and (c) sICAM-1 plasma levels do not represent a good marker of "cell activation" because they reflect activation of different cells and may be affected by different conditions.

Adult↗
PubMed1997

Noise reduction for NMR FID signals via Gabor expansion.

The parameters in a nuclear magnetic resonance (NMR) free induction decay (FID) signal contain information that is useful in biological and biomedical applications and research. A real time-sampled FID signal is well modeled as a finite mixture of modulated exponential sequences plus noise. We propose to use the generalized Gabor expansion for noise reduction, where the generalized Gabor expansion represents a signal in terms of a collection of time-shifted and frequency-modulated versions of a single sequence (prototype sequence). For FID signal-fitting, we choose the exponential sequence as the prototype function. Using the generalized Gabor expansion and exponential prototype sequences for FID model-fitting, an NMR FID signal can be well represented by the Gabor coefficients distributed in the joint time-frequency domain (JTFD). The Gabor coefficients reflect the weights of modulated exponential sequences in a signal. One of the important features is that the nonzero Gabor coefficients of a modulated exponential sequence will span a very small area in the JTFD, whereas the Gabor coefficients of the noise will not. If the exponent constant of the prototype sequence in the generalized Gabor expansion matches that of a modulated exponential sequence in the signal, then only one of the Gabor coefficients is nonzero in the JTFD. This is a very important property since it can be exploited to separate a signal from noise and to estimate modulated exponential sequence parameters.

Linear Models↗
PubMed1997

Delayed microbial keratitis following radial keratotomy.

BACKGROUND: We report on the case of a 46-year-old female who presented with delayed microbial keratitis 10 years after uncomplicated radial keratotomy. METHODS: The pre- and postoperative clinical record was reviewed following her presentation to the Corneal Clinic. Slit-lamp examination revealed a stromal inflammatory infiltrate at the site of an earlier radial keratotomy incision. The lesion was scraped and a coagulase-negative Staphylococcus aureus was cultured in enrichment broth. RESULTS: The keratitis was treated successfully with combination fortified topical antibiotics without loss of vision. CONCLUSIONS: Although microbial keratitis is a well documented complication of incisional refractive procedures, it is rarely encountered as late as one decade after surgery. Patients should be warned of this possibility and the need for prompt treatment.

Administration, Topical↗
PubMed1997

Soluble receptors to tumour necrosis factor and interleukin-6 in urine during acute pyelonephritis.

We compared the urinary concentrations of soluble TNF-I (sTNF-RI), TNF-II receptors, and soluble IL-6 receptor (sIL-6R) standardized to urinary creatinine concentrations, in children with acute pyelonephritis, in children with non-renal fever and in healthy controls. These levels were related to the acute inflammatory response in the kidneys and later renal scarring, as determined by acute and 1-y follow-up with 99mTC-dimercaptosuccinic acid scintigraphy (DMSA). The concentrations of the soluble receptors were measured using enzyme immunoassay (EIA). The urinary levels of sTNF-RI were significantly higher in children with acute pyelonephritis (median 1320 pg/mmol) than in children with non-renal fever, children 6 weeks after acute pyelonephritis and healthy controls (873, 251 and 477 pg/mumol, respectively). Median sTNF-RII urine levels were also higher in acute pyelonephritis (4123 pg/mumol) than in the three control groups (2000, 964 and 1850 pg/mumol, respectively). In contrast, the highest urinary sIL-6R concentrations were found in healthy children (median 420 pg/mumol), compared to those with acute pyelonephritis (235 pg/mumol), children with non-renal fever and children 6 weeks after pyelonephritis (137 and 50 pg/mumol, respectively). No significant difference was found in any of the urinary soluble receptor levels in children with or without DMSA uptake defects at the acute or the 1-y follow-up scintigraphy. In conclusion, although the urinary soluble TNF receptor levels were higher during acute pyelonephritis, this observation was not useful for deciding which children needed follow-up after acute pyelonephritis.

Acute Disease↗
PubMed1997

Analysis of the dose-surface histogram and dose-wall histogram for the rectum and bladder.

Dose distribution throughout a hollow organ is represented by either a dose-surface histogram (DSH) or a dose-wall histogram (DWH). A spherical shell model for the bladder and a cylindrical shell model for the rectum were introduced for quantifying the difference between the DWH and DSH. The difference was given by subtraction of the percent volume of the wall from the percent area of the surface for any specific dose level. Taking the dose-grid size and contour-delineation uncertainties into account, the DSH and DWH calculation errors were estimated by simplified formulas. The DSHs and DWHs for the rectum and bladder in patients undergoing four-field-prostate treatment and gynecological intracavitary brachytherapy were computed with a refined numerical algorithm. Results of the analytic models and the numerical calculations demonstrated that the difference between the DWH and DSH was small (about 5%) for a fully filled bladder or rectum but large (about 10%) for an empty rectum or a contracted bladder. The error of DSH was about 3%, which is smaller than that of DWH.

Humans↗
PubMed1997

Rhesus macaques previously infected with simian/human immunodeficiency virus are protected from vaginal challenge with pathogenic SIVmac239.

Nontraumatic vaginal inoculation of rhesus macaques with a simian/human immunodeficiency virus (SIV/HIV) chimera containing the envelope gene from HIV-1 89.6 (SHIV 89.6) results in systemic infection (Y. Lu, B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045-3050, 1996). A total of five rhesus macaques have each been infected by exposure to at least three intravaginal inoculations of SHIV 89.6. The SHIV 89.6 infection is characterized by a transient viremia that evokes humoral and cellular immune responses to HIV and SIV antigens, but disease does not develop in animals infected with SHIV 89.6. To determine if a previous infection with SHIV 89.6 by vaginal inoculation could protect animals from vaginal challenge with pathogenic SIV, all five animals were intravaginally inoculated twice with pathogenic SIV-mac239. After challenge, all of the SHIV-immunized animals had low or undetectable viral RNA levels in plasma compared to control animals. Three of the five of the SHIV-immunized animals remained virus isolation negative for more than 8 months, while two became virus isolation positive. The presence of SIV Gag-specific cytotoxic T lymphocytes in peripheral blood mononuclear cells and SIV-specific antibodies in cervicovaginal secretions at the time of challenge was associated with resistance to pathogenic SIV infection after vaginal challenge. These results suggest that protection from sexual transmission of HIV may be possible by effectively stimulating both humoral and cellular antiviral immunity in the systemic and genital mucosal immune compartments.

Animals↗
PubMed1997

Early increase of TNF alpha and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants.

AIM: To investigate if early changes in concentrations of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF) from preterm infants could be used to detect infants at risk of chronic lung disease (CLD) and help in the selection of patients for early steroid treatment. METHODS: Twenty eight preterm infants less than 34 weeks of gestation (median 26 weeks) were intubated and daily measurements of TAF concentrations of tumour necrosis factor alpha (TNF alpha) and the interleukins IL-1 beta, IL-6, and IL-8 were made, using enzyme immunoassay techniques. RESULTS: Seventeen of the infants developed CLD. The infants who developed CLD had significantly increased concentrations of TNF alpha, IL-1 beta, IL-6 on days 2 and 3. TNF alpha, IL-6, and IL-8 concentrations were significantly related to gestational age and duration of supplemental oxygen; TNF alpha, IL-6, and IL-8 concentrations also correlated with length of time on the ventilator. CONCLUSION: These data indicate that tracheobronchial aspirate fluid cytokine concentrations may be used as a predictor of subsequent CLD and may help select a group of preterm infants at high risk of developing CLD for early treatment.

Biomarkers↗
PubMed1997

Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages.

The role of nuclear factor (NF)-kappaB transcription factor in silica-induced cyclooxygenase (COX) II gene expression was examined in the rat alveolar macrophage cell line NR8383. Our results indicate that NF-kappaB can be activated in this cell line by silica exposure. Suppression of NF-kappaB activation in these cells leads to an attenuation of COX II mRNA accumulation induced by silica. Using an electrophoretic mobility shift assay and a reporter gene assay, we provide evidence that at least two kappaB sites in the 5'-flanking region of the rat COX II gene are involved for silica-induced transcriptional control of the COX II gene. The first motif, -404 GGGGATTCCC -395, is absolutely conserved in sequence and is localized in a similar position among the COX II genes found in humans, rats, and mice. The second motif, -91 GGGGAAAGCC -82, was conserved only in the mouse and rat COX II genes in sequence and in location. Aspirin, a COX inhibitor, was shown to suppress silica-induced NF-kappaB activation. However, prostaglandin E2, one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-kappaB activation by retarding the degradation of silica-induced inhibitor NF-kappaB. These results suggest that an interdependent regulation may exist between NF-kappaB activation and COX or its products.

Animals↗
PubMed1997

Comparisons of noninvasive bone mineral measurements in assessing age-related loss, fracture discrimination, and diagnostic classification.

The purpose of this study was to examine the commonly available methods of noninvasively assessing bone mineral status across three defined female populations to examine their interrelationships, compare their respective abilities to reflect age- and menopause-related bone loss, discriminate osteoporotic fractures, and classify patients diagnostically. A total of 47 healthy premenopausal (age 33 +/- 7 years), 41 healthy postmenopausal (age 64 +/- 9 years), and 36 osteoporotic postmenopausal (age 70 +/- 6 years) women were examined with the following techniques: (1) quantitative computed tomography of the L1-L4 lumbar spine for trabecular (QCT TRAB BMD) and integral (QCT INTG BMD) bone mineral density (BMD); (2) dual X-ray absorptiometry of the L1-L4 posterior-anterior (DXA PA BMD) and L2-L4 lateral (DXA LAT BMD) lumbar spine, of the femoral neck (DXA NECK BMD) and trochanter (DXA TROC BMD), and of the ultradistal radius (DXA UD BMD) for integral BMD; (3) peripheral QCT of the distal radius for trabecular BMD (pQCT TRAB BMD) and cortical bone mineral content (BMC) (pQCT CORT BMC); (4) two radiographic absorptiometric techniques of the metacarpal (RA METC BMD) and phalanges (RA PHAL BMD) for integral BMD; and (5) two quantitative ultrasound devices (QUS) of the calcaneus for speed of sound (SOS CALC) and broadband ultrasound attenuation (BUA CALC). In general, correlations ranged from (r = 0.10-0.93) among different sites and techniques. We found that pQCT TRAB BMD correlated poorly (r < or = 0.46) with all other measurements except DXA UD BMD (r = 0.62,p < or = 0.0001) and RA PHAL BMD (r = 0.52, p < or = 0.0001). The strongest correlation across techniques was between QCT INT BMD and DXA LAT BMD (r = 0.87, p < or = 0.0001), and the weakest correlation within a technique was between pQCT TRAB BMD and pQCT CORT BMC (r = 0.25,p < or = 0.05). Techniques showing the highest correlations with age in the healthy groups also showed the greatest differences among groups. They also showed the best discrimination (as measured by the odds ratios) for the distinction between healthy postmenopausal and osteoporotic postmenopausal groups based on age-adjusted logistic regression analysis. For each anatomic site, the techniques providing the best results were: (1) spine, QCT TRAB BMD (annual loss, -1.2% [healthy premenopausal and healthy postmenopausal]); Student's t-value [not the T score], 5.4 [healthy postmenopausal vs. osteoporotic postmenopausal]; odds ratio, 43 [age-adjusted logistic regression for healthy postmenopausal vs. osteoporotic postmenopausal]); (2) hip, DXA TROC BMD (-0.46; 3.5; 2.2); (3) radius, DXA UD BMD (-0.44; 3.3; 1.9) and pQCT, CORT BMC (-0.72; 2.9; 1.7); (4) hand, RA PHAL (-0.51; 3.6; 2.0); and (5) calcaneus, SOS (-0.09; 3.4; 2.1) and BUA (-0.52; 2.6; 1.7). Despite these performance trends, the differences among sites and techniques were statistically insignificant (p > 0.05) using age-adjusted receiver operating characteristic (ROC) curve analysis. Nevertheless, kappa score analysis (using -2.0 T score as the cut-off value for osteopenia and -2.5 T score for osteoporosis) showed that in general the diagnostic agreement among these measurements in classifying women as osteopenic or osteoporotic was poor, with kappa scores averaging about 0.4 (exceptions were QCT TRAB/INTG BMD, DXA LAT BMD, and RA PHAL BMD, with kappa scores ranging from 0.63 to 0.89). Often different patients were estimated at risk by using different measurement sites or techniques.

Absorptiometry, Photon↗
PubMed1997

Universal standardization of bone density measurements: a method with optimal properties for calibration among several instruments.

The International Dual-Photon X-Ray Absorptiometry (DXA) Standardization Committee (IDSC) conducted a cross-calibration study among three models of DXA machines from three different manufacturers. In that study, 100 subjects were scanned on all three machines. A set of equations were derived to convert bone mineral density (BMD) on each machine to a "standardized BMD" (sBMD) such that sBMD from the same subject derived from different machines would be approximately the same. In a reanalysis of the cross-calibration data, we showed that the conversion method used in the IDSC study did not achieve several optimal properties desirable in such conversions. We derived new conversion equations to sBMD based on minimizing differences among sBMD from the three machines. More important is that the new conversions have no residual bias that was present in the IDSC conversions. The performance of the methods were compared on the cross-calibration data as well as an external data set. We conclude that the IDSC conversions are adequate for clinical use on other machines worldwide, but that researchers should standardize their own machines in a laboratory using the new method.

Absorptiometry, Photon↗
PubMed1997

HIV-1 vaccine candidate evaluation in non-human primates.

The development of an HIV-1 vaccine in the last 13 years from an industrial point of view has focused on evaluating potential vaccine candidates in non-human primates. This review discusses the HIV-1 vaccine candidates that have been tested in chimpanzees or monkeys and includes those based on recombinant gp120, recombinant gp160, different viral and bacterial vectors expressing gp120, gp160, or only V3 peptide, naked DNA vaccines, and whole inactivated viruses. To help understand the result of efficacy studies in chimpanzees and monkeys, information regarding the challenge viruses used in these studies is also included. The review does not discuss the testing of SIV-related vaccines or the testing of HIV-1 vaccine candidates in other animal species other than non-human primates.

AIDS Vaccines↗
PubMed1997

[The effect of exercise on the androgen receptor binding capacity and the level of testosterone in the skeletal muscle].

Androgen receptor (AR) binding and testosterone (T) level of skeletal muscle of rat at the different conditions were observed in this study. The exhausted exercise could up-regulate the AR binding of levator ani muscle, but decrease the T level in quadriceps. The long term exhausted exercise had no effect on the AR binding of quadriceps. The fitness exercise could up-regulate the AR binding of quadriceps but have no significant effect on the T level in quadriceps. There was no effect on the AR binding but T level was increased after injection of HCG for 4 days in quadriceps. The increase of T level in skeletal muscle after injection of HCG for 4 days was higher than that for 8 days. From these results it is suggested that the effect of exercise on the regulation of hormone on skeletal muscle may be in two directions. Both AR binding capacity and T level must be considered in skeletal muscle anabolism.

Animals↗
PubMed1997

Virtual cancer image data warehouse.

We previously developed a system with which we have created more than 100 virtual cancer images from CT or MR data of individual patients with cancer (Cancer Edutainment Virtual Reality Theater: CEVRT). These images can be used to help explain procedures, findings, etc. to the patient, to obtain informed consent, to simulate surgery, and to estimate cancer invasion to surrounding organs. We recently developed a web-based object-oriented database both to access these cancer images and to register medical images at international research sites via the Internet. In this report, we introduce an international medical VR data warehouse created using an object-oriented database.

Audiovisual Aids↗