Biomedical subjects

W Tu

Publications and source records attributed to W Tu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Long-term immunological memory in the resistance of rats to transplanted intracerebral 9L gliosarcoma (9LGS) following subcutaneous immunization with 9LGS cells.

Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About 7000 new cases are diagnosed yearly in the USA. Despite current neurosurgical and postoperative radiotherapeutic tumor cytoreduction methods, in most cases occult foci of tumor cells infiltrate surrounding edematous brain tissues and cause recurrent disease within one year. GBM is almost invariably fatal within a few years after it is diagnosed. Our goal is to achieve long-term control of GBM by combining immunoprophylaxis with a radiation-based technique, such as boron neutron-capture therapy (BNCT), potentially capable of specifically targeting the infiltrating tumor cells while sparing the surrounding normal brain tissue. It has long been known that the subcutaneous (sc) injection of irradiated cells or untreated cultured cells (and the removal of the resulting tumors) derived from the well characterized, highly immunogenic 9L gliosarcoma (9LGS) rat model into young isogenic rats can prevent tumor growth after subsequent sc or intracranial (ic) injection of untreated, otherwise lethal 9LGS cells. In this study we have confirmed, quantified and extended those findings to study the efficacy of such immunological memory in normal aging rats and in aging rats previously treated for ic 9LGS tumors by BNCT. (1) The sc injection of 5,000,000 untreated 9LGS cells and the surgical removal of the resulting tumors (method A) protected 80% of normal young rats from an ic challenge with 10,000 untreated 9LGS cells, and a single sc injection of 5,000,000 lethally X-irradiated 9LGS cells (method B) protected 66% of them, but multiple sc injections with a crude particulate fraction prepared from 9LGS cells were not protective. Protection is long-lasting since contralateral ic rechallenge of six-month survivors with an injection of 10,000 viable 9LGS cells resulted in 100% survival. (2) Normal one-year-old rats were only slightly less protected than were normal young rats, approximately 70% rather than approximately 80% (method A) and approximately 60% rather than approximately 66% (method B). (3) BNCT treatment alone resulted in partial immunological protection, as 30% of one-year post-BNCT survivors of ic 9LGS tumors prevailed after contralateral ic rechallenge with 10,000 viable 9LGS cells. Moreover a single sc immunization with 5,000,000 untreated 9LGS cells prior to ic rechallenge boosted survival from 30% to 100%. The relevance of these observations to strategies of preclinical experimentation for immunoprophylaxis of malignant gliomas is discussed.

Animals↗

PubMed2000

p53 accumulation due to down-regulation of ubiquitin: relevance for neuronal apoptosis.

The p53 tumor suppressor protein is a major regulator of cell growth arrest and apoptosis in response to DNA damage. Both p53 function and stability are tightly controlled by Mdm2, which binds to the p53 N-terminus and targets p53 for ubiquitin-mediated proteolysis. Previous studies suggest that adrenalectomy-induced neuronal apoptosis is p53-dependent. Here we demonstrate both nuclear accumulation and functional activation of p53 protein in apoptotic hippocampal neurons from adrenalectomized rats. Increased p53 expression occurred despite the accumulation of its negative regulator, Mdm2, and the formation of p53-Mdm2 complexes. The persistence of p53 expression was explained by a striking decrease in free ubiquitin in p53-positive neurons. The addition of exogenous ubiquitin to p53-Mdm2 complexes from apoptotic neurons restored p53 degradation. These findings demonstrate a novel mechanism of p53 stabilization mediated by decreased ubiquitin levels. Regulation of free ubiquitin may therefore be an effective way to modulate p53-dependent apoptosis in certain cell types.

Adrenalectomy↗

PubMed2000

Confidence intervals for the mean of diagnostic test charge data containing zeros.

In this paper, we consider the problem of interval estimation for the mean of diagnostic test charges. Diagnostic test charge data may contain zero values, and the nonzero values can often be modeled by a log-normal distribution. Under such a model, we propose three different interval estimation procedures: a percentile-t bootstrap interval based on sufficient statistics and two likelihood-based confidence intervals. For theoretical properties, we show that the two likelihood-based one-sided confidence intervals are only first-order accurate and that the bootstrap-based one-sided confidence interval is second-order accurate. For two-sided confidence intervals, all three proposed methods are second-order accurate. A simulation study in finite-sample sizes suggests all three proposed intervals outperform a widely used minimum variance unbiased estimator (MVUE)-based interval except for the case of one-sided lower end-point intervals when the skewness is very small. Among the proposed one-sided intervals, the bootstrap interval has the best coverage accuracy. For the two-sided intervals, when the sample size is small, the bootstrap method still yields the best coverage accuracy unless the skewness is very small, in which case the bias-corrected ML method has the best accuracy. When the sample size is large, all three proposed intervals have similar coverage accuracy. Finally, we analyze with the proposed methods one real example assessing diagnostic test charges among older adults with depression.

Biometry↗

PubMed2000

[Influences of BN50739 on neutrophil elastase and phospholipase A2 in lung and tracheal mucosa of pigs with acute severe pancreatitis].

OBJECTIVE: To investigate the effects of platelet-activating factor (PAF) and a new potent PAF-receptor antagonist, BN50739, on the activities of neutrophil elastase and phospholipase A2 (PLA2) in lung and tracheal mucosa of pigs with acute severe pancreatitis (ASP) induced by sodium taurocholate. METHODS: There were twenty eight pigs weighing 16-22 kg, which were divided into five groups. Group I (n = 5): sham-control; Group II (n = 6): ASP-control; Group III (n = 5): DMSO-control; Group IV (n = 6) and Group V (n = 6): pre- and post-treatment with BN50739. Anesthesized pigs were subjected to ASP induced by injecting 1 ml/kg of combined solution of 5% sodium taurocholate and 8,000-10,000 BAEE units trypsin/ml into pancreas via pancreatic duct. All pigs were sacrificed by injecting 20 ml of 10% KCl intravenously. Specimens of lung and tracheal mucosa were removed, weighed and homogenized in grinding tubes. The homogenate was centrifuged and the supernatants were collected for the assays of NE, PLA2, MPO and PAF. RESULTS: The activities of NE, PLA2 and MPO and the levels of PAF in lung and tracheal mucosa increased significantly in ASP pigs. There are significantly positive relationships between PAF and NE, PLA2, MPO or W/D in lung and tracheal mucosa. The PAF levels in lung and tracheal mucosa and the severity of acute lung injury induced by PMN sequestration, NE and activated PLA2 reduced remarkably by the pre- and post-treatment with BN50739. CONCLUSIONS: PAF plays an important role in acute lung injury in porcine ASP, which may be associated with the increments of PMN sequestration, NE and the highly activated PLA2 in lung and tracheal mucosa. The pre- and post-treatment with BN50739 can effectively reduce the PAF levels in lung and tracheal mucosa and the severity of acute lung injury following ASP via reducing the PMN sequestration and the amount of elastase, and by inhibiting PLA2 activities in lung and tracheal mucosa.

Animals↗

PubMed2000

Effects of platelet activating factor antagonist (BN50739) on gut mucosal injury in acute severe pancreatitis in pigs.

OBJECTIVE: To study the role of platelet activating factor (PAF) in the pathogenesis of intestinal mucosal injury and endotoxin/bacterial translocation in acute severe pancreatitis (ASP) in pigs. METHODS: ASP was induced by intraductal injection of a mixture of sodium taurocholate and trypsin. BN50739, a specific antagonist of PAF, was given 30 min prior to the induction of ASP. Mucosal blood flow, mucosal myeloperoxidase (MPO) and malondialdehyde (MDA) were determined. Intestinal injury was observed microscopically. Portal blood endotoxin levels and the bacterial counts in the portal blood, intestinal lymph nodes and the pancreas were determined. RESULTS: Prior antagonism of PAF by BN50739 reduced intestinal injury, increased intestinal mucosal blood flow, and reduced blood levels of endotoxin and bacterial counts in the portal blood, mesenteric lymph nodes and pancreas. CONCLUSIONS: Intestinal mucosal injury developed in ASP. PAF is responsible for the injury. Antagonism of PAF by BN50739 can improve intestinal microcirculation and reduce the severity of intestinal mucosal injury, which may decrease endotoxin/bacterial translocation.

Acute Disease↗

PubMed1999

A Wald test comparing medical costs based on log-normal distributions with zero valued costs.

Medical cost data often exhibit strong skewness and sometimes contain large proportions of zero values. Such characteristics prevent the analysis of variance (ANOVA) F-test and other frequently used standard tests from providing the correct inferences when the comparison of means is of interest. One solution to the problem is to introduce a parametric structure based on log-normal distributions with zero values and then construct a likelihood ratio test. While such a likelihood ratio test possesses excellent type I error control and power, its implementation requires a rather complicated iterative optimization program. In this paper, we propose a Wald test with simple computation. We then conduct a Monte Carlo simulation to compare the type I error rates and powers of the proposed Wald test with those of the likelihood ratio test. Our simulation study indicates that although the likelihood ratio test slightly outperforms the Wald test, the performance of the Wald test is also satisfactory, especially when the sample sizes are reasonably large. Finally, we illustrate the use of the proposed Wald test by analysing a clinical study assessing the effects of a computerized prospective drug utilization intervention on in-patient charges.

Analysis of Variance↗

PubMed1999

Work patterns of ambulatory care pharmacists with access to electronic guideline-based treatment suggestions.

The effects of the electronic display of guideline-based, patient-specific treatment suggestions on pharmacist work patterns were studied. A total of 28 pharmacists at a hospital-based ambulatory care pharmacy were randomly assigned to intervention and control groups. The intervention group had access to electronic treatment suggestions for heart failure, ischemic heart disease, reactive airways disease, and uncomplicated hypertension, while the control group did not. Starting 9 and 19 months after the initial display of treatment suggestions, all pharmacists recorded the time they spent on a variety of activities, the purpose of each activity, and persons contacted during the activity; these observations were recorded in response to a pager-like device that randomly buzzed four times an hour. A total of 11,102 observations were recorded. Pharmacists in the intervention group spent significantly more of their time discussing information, advising and informing, and solving problems than pharmacists in the control group but significantly less of their time checking and filling prescriptions. Pharmacists in both groups completed a majority of their work alone, but pharmacists in the intervention group worked significantly less by themselves and significantly more with other pharmacy personnel, patients, and physicians and nurses than control-group pharmacists. The delivery of patient-specific information to pharmacists at the time of dispensing had a significant positive impact on pharmacist work patterns.

Clinical Pharmacy Information Systems↗

PubMed1999

An enhancement of nitric oxide production regulates energy metabolism in rat hepatocytes after a partial hepatectomy.

BACKGROUND/AIMS: Infection after a liver resection often results in hepatic failure. Nitric oxide is one of the candidates which has been suspected to cause cellular dysfunction during infection in the liver. We have previously reported that the inflammatory cytokine interleukin-1beta (IL-1beta) induced the expression of the inducible nitric oxide synthase gene in primary cultured rat hepatocytes. We hypothesized that an enhancement of nitric oxide production after the resection was implicated in a change in liver energy metabolism, thus resulting in liver dysfunction. METHODS: In this study, we performed a 70% hepatectomy or a sham operation in rats, and then isolated hepatocytes from the remnant liver by collagenase perfusion. The cultured hepatocytes were treated with cytokines including IL-1beta. The effects on nitric oxide induction, the ATP content and ketone body ratio (acetoacetate/beta-hydroxybutyrate) were then compared between the partial hepatectomized (PH) and sham-operated (control) rats. RESULTS: IL-1beta augmented the induction of nitric oxide production two-fold in hepatocytes from the PH rats as compared to the control rats. IL-1beta markedly decreased the ATP content in the PH rats, although IL-1beta also decreased the ATP content in the control rats, but to a lesser extent. IL-1beta also decreased the ketone body ratio in both groups. The addition of L-arginine further stimulated the inhibition of the ATP levels and the ketone body ratio concomitantly with increased nitric oxide production in the PH rats. N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, abolished the effects of IL-1beta on the ATP levels and ketone body ratio, as well as on the nitric oxide production. CONCLUSIONS: These results demonstrate that the decreased ATP content observed in PH rats resulted from an increase in nitric oxide production. The decrease in ketone body ratio indicates that nitric oxide-induced mitochondrial dysfunction contributes significantly to ATP attenuation in hepatocytes. Therefore, the regulation of nitric oxide induction may be crucial for preventing liver failure after a hepatic resection.

Adenosine Diphosphate↗

PubMed1999

Effect of insulin-like growth factor 1 on PHA-stimulated cord blood mononuclear cell telomerase activity.

Telomerase may contribute to the capacity for cell replication by compensating for the loss of telomere length. Exploring the use of biological modifiers in increasing cellular replicative potential through telomerase activity may be useful for in vitro expansion of haemopoietic stem cells for transplantation or lymphoid cells for adoptive immunotherapy. In this study we showed for the first time that insulin-like growth factor 1 (IGF-1) modulated telomerase activity in human cord blood mononuclear cells (MNC) and some of the known functional determinants of telomerase activity. We found that cord blood MNC expressed constitutively a low level of telomerase activity and human telomerase reverse transcriptase (hTRT) mRNA, and a high level of human telomerase RNA component (hTR) and telomerase-associated protein-1 (TP1) mRNA. Interestingly, IGF-I alone did not increase the telomerase activity of cord blood MNC but could enhance the PHA-induced increase in telomerase activity. These alterations in telomerase activity were not completely in phase with those of proliferation response. On the other hand, IGF-I did not alter hTRT mRNA expression but enhanced the PHA-induced increase in hTRT whereas TP1 mRNA expression was stimulated by either IGF-I or PHA but showed no additive increase when stimulated by both IGF-1 and PHA. Neither IGF-1 nor PHA altered hTR expression. Finally, the temporal dynamics of hTRT mRNA expression and telomerase activity in cord blood MNC over 5 d in culture were not totally concordant. suggesting that key factors other than hTRT were involved in regulating telomerase activity in cord blood MNC. The modulatory effect of IGF-1 on telomerase activity supports its potential role in increasing replicative potential of cord blood lymphoid cells or haemopoietic stem cells.

Cell Division↗

PubMed1999

Acceptance of skin allografts in pigs by portal venous injection of donor bone marrow cells.

OBJECTIVE: To confirm in pigs whether a new method for organ allografts, originally established in mice by the authors, might be applicable to humans. SUMMARY BACKGROUND DATA: The authors recently established a new method for organ allografts in mice that includes the injection of donor bone marrow cells (BMCs) using the portal vein (PV), followed by the administration of cyclosporin A (CsA) on days 2 and 5, and the intravenous injection of BMCs on day 5. In the present study, they modify this method (a single-day protocol) and apply it to pigs. METHODS: Allogeneic BMCs of donor pigs were injected using the PV (a superior mesenteric vein). The skin grafting was carried out on the day of the PV injection. The recipient pigs received donor grafts, autologous grafts, and third-party grafts at the same time. In addition, an open wound was made as the epithelized control. Full-thickness skin grafts were harvested from the dorsal wall of the donors. CsA (10 mg/kg) was injected intramuscularly into recipient pigs on days 2 and 5 after the PV injection. RESULTS: One hundred percent of skin grafts survived for >300 days when donor BMCs were injected using the PV (n = 6). However, the skin grafts of the three pigs that had received BMCs using the intravenous route were rejected within 3 to 4 weeks after transplantation. The third-party skin grafts showed necrotic changes on day 21 after transplantation. CONCLUSIONS: One hundred percent of skin allografts can be obtained, even in pigs, by injecting donor BMCs using the PV, carrying out skin allografts, and administering CsA on days 2 and 5. This single-day protocol would be of great advantage for human organ transplantation.

Animals↗

PubMed1999

Comparison of several independent population means when their samples contain log-normal and possibly zero observations.

In this paper, we consider the problem of testing the mean equality of several independent populations that contain log-normal and possibly zero observations. We first showed that the currently used methods in statistical practice, including the nonparametric Kruskal-Wallis test, the standard ANOVA F-test and its two modified versions, the Welch test and the Brown-Forsythe test, could have poor Type I error control. Then we propose a likelihood ratio test that is shown to have much better Type I error control than the existing methods. Finally, we analyze two real data sets that motivated our study using the proposed test.

Biometry↗

PubMed1999

IGF-I increases interferon-gamma and IL-6 mRNA expression and protein production in neonatal mononuclear cells.

Neonates are vulnerable to infections because of their immature immunity. IGF-I has been reported to have profound positive effects on immune function. In this study, we investigated the effects of IGF-I on neonatal immunity. The production of IL-2, IL-4, and interferon-gamma in phytohemagglutinin (PHA)-stimulated neonatal mononuclear cells (MNC) was significantly decreased when compared with that of adults. IGF-I alone induced a high level of IL-6 mRNA expression and protein production in neonatal MNC. IGF-I significantly increased mRNA expression and protein production of both IL-6 and interferon-y but had no influence on that of IL-2 and IL-4 in PHA-stimulated neonatal MNC. Moreover, it increased neonatal interferon-gamma production in PHA-stimulated MNC to a level similar to that of adults. IGF-I could further enhance the mRNA expression of lymphocyte-activation gene 3, which is associated with interferon-gamma production and differentiation of T-helper 1 lymphocytes, in PHA-stimulated neonatal MNC. These results suggest IGF-I could promote maturation of neonatal T cells, and its potential use to enhance neonatal immunity deserves further study.

Adult↗

PubMed1999

[Development of continuous rat infusion device].

In order to perform better scientific researches on fluid resuscitation, total parenteral nutrition and continuous drug administration in rats, we developed a set of rat infusion device. The device, the characteristics of reasonable design, simple operation, low cost, good practicability, and making it by oneself or buying a whole set, can not only assure rats to run around, drink water, eat food freely, but also insure continuous infusion and drug administration during the experimental study of rats.

Animals↗

PubMed1998

[Determination of vincristini sulfas in tumor cells by high performance liquid chromatography].

Vincristini sulfas (VCR) is an important common antitumor drug. The resistance to anticancer drug is the main cause of the chemotherapy failure. To screen the drugs which can reverse VCR resistance for VCR resistant cell strain, an analytical method has been established for the determination of VCR concentration in tumor cells using high performance liquid chromatography (HPLC). The stainless steel column was 25 cm x 4.6 mm i.d. packed with totally porous, spherical silica particles (5 microns). A solution of methanol and 0.02 mol/L dipotassium hydrogen phosphate (80:20, V/V) adjusted to pH 6.6 with H3PO4 was employed as the mobile phase. The flow rate was 1 mL/min. Chromatography was performed with ultraviolet detector at 267 nm. The method is simple, rapid and selective. Linear calibration curve for VCR was measured within the range of 10 to 200 mg/L with correlation coefficient of 0.999 8. The lowest detection limit was 4 mg/L tumor cells extract. The HPLC method described is suitable for clinical monitoring and pharmacokinetic study of VGR.

Antineoplastic Agents, Phytogenic↗

PubMed1998

[Development and clinical significance of SEA-1 emergency micro-ventilator].

To improve the work of emergency care and early cardio-pulmonary-brin resuscitation in our county, which is characteristic of abruptness and contingency, a new type of ventilator is highly required. It is hoped that such a ventilafor has a simple safe valve and does not need electric current from the mains. Also, the ventilator should be small in size, light in weight, simple in operation, easy to carry, swift to assembly, and reliable in ventilation. With the principle of pneumatic logic elements and the design of the integration of pneumatic circuits, we have successfully developed the Emergency Micro-ventilator, which accords with the above requirements. It has been confirmed that the ventilator is very effectual and reliable in ventilation support for the patients(n = 55) under general anesthesia without any case of hypoxemia, hypercapnia, hypotension, arrhythmia and so on, and the mechanical performances are stable.

Equipment Design↗

PubMed1997

Human cytomegalovirus matrix protein PP150 is efficiently presented as one of target antigens for cytotoxic T lymphocyte recognition.

OBJECTIVE: To determine whether human cytomegalovirus (CMV) matrix protein PP150 is efficiently presented for CMV-specific CTL recognition. METHODS: Recombinant vaccinia virus (Vac. PP150) encoding human CMV structural matrix protein PP150 was constructed with vaccinia vector PSC11 and it was used to stimulate peripheral blond mononuclear cells from 5 CMV seropositive individuals. RESULTS: PP150-specific CTLs could be generated in all of them, which not only lysed Vac. PP150-infected fibroblasts, but also lysed CMV-infected targets. In the presence of RNA synthesis inhibitor Actinomycin D (Act D) or at very early stage of infection, PP150-specific CTL lysed CMV-infected targets as efficiently as in the absence of Act D or at late stage of infection. CONCLUSIONS: PP150 exogenously introduced with the virus infection could be efficiently presented prior to viral DNA replication and PP150 is one of the major target antigens for CTL recognition.

Antigens, Viral↗

PubMed1996

Hepatocyte volume as an indicator of hepatic functional reserve in cirrhotic patients with liver tumours.

Using computed tomography (CT), measurements of whole liver volume have been used for the assessment of pre-operative functional reserve in cirrhotics. However, measurements of hepatocyte volume, which exclude stromal fibrous tissue, are considered to more directly reflect hepatic functional reserve. We investigated the relationship between total hepatocyte volume and each of the parameters of conventional liver function. Indocyanine green (ICG) tests and blood analyses for the assessment of liver function were performed prior to surgery in cirrhotic patients with liver tumours. Pre-operative liver volume was determined by integrating images of each liver area obtained by CT. Liver area was measured by an image processing program that traced the profile of the liver image while excluding the tumorous area. Sections of normal tissue stained by the haematoxylin-eosin method, were obtained from the resected liver. Using these sections, a hepatocyte area: whole tissue area ratio was calculated using the image processing program, by tracing the profiles of the hepatocyte nodules. The total volume of hepatocytes was then calculated by multiplying the liver volume by this ratio. The hepatocyte volume per unit bodyweight was significantly correlated with ICG tests and with many other parameters of normal liver function. However, the liver volume per unit bodyweight was correlated only with the plasma ICG disappearance rate and with the blood platelet count. These observations suggest that the functional reserve of the cirrhotic liver is assessed more precisely by hepatocyte volume than by liver volume.

Adult↗

PubMed1996

[Selective thermocoagulation of unresectable malignant tumors using radiofrequency].

Based on our experimental findings on porcine liver, we have been conducting a clinical trial of selective hyperthermia by radiofrequency (RF) capacitive heating with laparotomy for patients with unresectable malignant tumors. In 10 patients with malignant tumors (8 carcinoma of the pancreas, 2 carcinoma of the gallbladder), laparotomy and RF heating were performed after informed consent. The local heat coagulation was produced by heating equipment using 13.56 MHz radiofrequency produced by Omron Corporation, Japan. Four 2-cm electrode needles were placed in the tumor in a square array at intervals of 2.0 cm. Hyperthermia was given for 30 min with a controlled temperature of 50 degrees C in the RF field (2 x 2 x 2 cm3). That of the surrounding area was maintained at less than 40 degrees C. The calculated volume treated by RF ranged between (2 x 2 x 2 cm3) x 1 and (2 x 2 x 2 cm3) x 6. We followed all patients by computed tomographic (CT) scan 2 weeks after coagulation. Tumor markers in the blood were assayed before and 14 days after heating. Follow-up CT scans demonstrated that after the tumor mass had been heterogeneously enhanced, it changed to a homogeneous low-density area in 6 of 10 patients. The levels of tumor markers decreased to lower than the pre-treatment values in 9 of 10 patients. In all patients, the changes in CT scans and/or decrease in the markers were confirmed. Complications such as bleeding or abscess formation were not observed. It was suggested that the selective hyperthermia was safely produced by this equipment. The encouraging results in these patients justify further clinical trials.

Biomarkers, Tumor↗