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Biomedical subjects

Q Le

Publications and source records attributed to Q Le.

13 recordsLinked to original sources
PubMed2001

Daily low-dose carboplatin as a radiation sensitizer for newly diagnosed malignant glioma.

Surgical resection followed by local field radiotherapy is currently our most effective approach to treatment for most patients with malignant glioma. Carboplatin chemotherapy has direct cytotoxic effects on glioma cells and acts as a radiation sensitizer to enhance cell killing. Its demonstrated efficacy as a sensitizer in other solid tumors led to this clinical trial of carboplatin as a radiation sensitizer in the treatment of newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Fourteen patients (nine GBM and five AA) were treated with daily low-dose carboplatin 25 mg/m2 intravenously within 2 h of their fractionated radiotherapy to a total dose of 600 mg/m2. No significant toxicities attributable to this combined therapy were observed. All patients have progressed, with median time to progression of 16 weeks. Eleven patients have died, with median survival of 38 weeks for the entire cohort. Although this regimen appeared safe, there was no benefit in survival time compared to historical patients treated with radiotherapy. The limitations and future potential for the strategy of radiation sensitization are discussed.

Adult↗
PubMed2001

Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons.

Estrogen is an active neuroprotectant and is presently investigated as a potential therapy against Alzheimer's disease for women. To determine if male hormones could also be neuroprotective, we investigated the effect of testosterone, methyltestosterone, and epitestosterone at physiological concentrations on primary cultures of human neurons induced to undergo apoptosis by serum deprivation. Serum deprivation significantly induces neuronal apoptosis in a protracted fashion. As expected, physiological concentrations of 17-beta-estradiol and transcriptionally inactive 17-alpha-estradiol protect neurons against apoptosis. Similar to 17-beta-estradiol, physiological concentrations of testosterone are also neuroprotective. Androgen receptors are present at 8 +/- 2 fmol/mg protein in the neuron cultures. The non-aromatizable androgen, mibolerone, is also neuroprotective and aromatase inhibitor, 4-androsten-4-OL-3,17-dione, does not prevent testosterone-mediated neuroprotection. In contrast, anti-androgen, flutamide, eliminates testosterone-mediated neuroprotection. Testosterone analog, methyltestosterone, showed androgen receptor-dependent neuroprotection that was delayed in time indicating that a metabolite may be the active agent. The endogenous anti-androgen, epitestosterone, also showed a slight neuroprotective effect but not through the androgen receptor. These results indicate that androgens induce neuroprotection directly through the androgen receptor. These data suggest that androgens may also be of therapeutic value against Alzheimer's disease in aging males.

Androgen Antagonists↗
PubMed2001

[Effects of nitric oxide and prostaglandin on gastric mucosal perfusion in rats with portal hypertensive gastropathy].

OBJECTIVE: To observe the effects of nitric oxide (NO) and prostaglandin on gastric mucosal perfusion in rats with portal hypertensive gastropathy (PHG). METHODS: Two weeks after partial portal vein ligation, gastric mucosal blood flow (GMBF) was measured with the neutral red clearance method and the changes of portal venous pressure (PVP) were observed. RESULTS: GMBF and PVP were significantly higher in rats with PHG than in sham operated rats (P<0.01). Low dose inhibitor of NO synthesis N(-nitro-L-arginine methyl ester (L-NAME 1mg/kg, 4mg/kg) caused a significant and dose dependent reduction in GMBF in PHG rats, but had no effect on sham operated rats. High dose L-NAME (12 mg/kg) significantly decreased GMBF in both PHG and sham operated rats. The inhibition of prostaglandin synthesis with indomethacin significantly decreased GMBF in rats with PHG, but had no effect in sham operated rats. In sham operated rats pretreated with indomethacin, GMBF was not modified after and before injection of low dose L-NAME (4mg/kg); likewise, high dose of L-NAME (12mg/kg) did not alter the significant reduction in GMBF as compared with pretreatment without indomethacin. In PHG rats the significant dose dependent reduction in GMBF induced by L-NAME (4mg/kg, 12mg/kg) was not significantly different between pretreatment with and without indomethacin. CONCLUSIONS: NO and prostaglandins play an important role in the regulation of GMBF in rats with PHG, but no synergistic interactions between them.

Animals↗
PubMed2000

Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids.

Retinoids have been shown to inhibit the growth of many human tumor cells including breast, ovarian and squamous cell carcinoma (SCC). While the exact mechanism of retinoid mediated growth suppression is not known, a role for the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) has been established in both the breast and ovarian tumor cell models. We set out to determine if modulation of RAR/RXR function would alter the retinoid sensitivity of oral SCC cells. We found that the growth of SCC cells was significantly inhibited by treatment with either all-trans-retinoic acid (trans-RA) or the synthetic, conformationally restricted RARgamma selective retinoids MM11254 and MM11389. In order to demonstrate a role for RAR/RXR function in this process, stable oral SCC cell clones constitutively overexpressing the dominant negative mutant RARbeta2 (R269Q) were prepared and shown to exhibit reduced RAR/RXR transcriptional transactivation activity. We found that oral SCC cells exhibiting reduced RAR/RXR function became resistant to growth inhibition by all-trans-RA, MM11254 and MM11389. Likewise, treatment of oral SCC cells with the RARgamma antagonist MM11253 was found to block the ability of MM11254 and MM11389 to inhibit SCC cell growth. Thus, modulation of RAR function through the use of RAR-gamma selective agonists, an RAR-gamma selective antagonist or a pan-RAR dominant negative mutant significantly alters the growth inhibitory response of oral SCC cells to retinoids.

Arginine↗
PubMed2000

Image-guided radiosurgery for the spine and pancreas.

A robotic image-guided radiosurgical system has been modified to treat extra-cranial sites using implanted fiducials and skeletal landmarks to locate the treatment targets. The system has been used to treat an artero-venous malformation in the cervical spine, a recurrent schwannoma of the thoracic spine, a metastatic adenocarcinoma of the lumbar spine, and three pancreatic cancers. During each treatment, the image guidance system monitored the position of the target site and relayed the target coordinates to the beam-pointing system at discrete intervals. The pointing system then dynamically aligned the therapy beam with the lesion, automatically compensating for shifts in target position. Breathing-related motion of the pancreas lesions was managed by coordinating beam gating with breath-holding by the patient. The system maintained alignment with the spine lesions to within +/- 0.2 mm on average, and to within +/- 1 mm for the pancreatic tumors. This experience has demonstrated the feasibility of using image-guided robotic radiosurgery outside the cranium.

Adenocarcinoma↗
PubMed2000

[Effects of sandostatin on gastric mucosal perfusion in rats with portal hypertensive gastropathy].

OBJECTIVE: To observe the effects of sandostatin on gastric mucosal blood flow (GMBF) in rats with (portal hypertensive gastropathy, PHG) and its mechanisms. METHODS: Two weeks after portal vein ligation, the changes of systemic hemodynamics, GMBF, (portal vein pressure, PVP) were observed and plasma glucagon, plasma and gastric mucosal NO2-/NO3-, 6-Keto-PGF(1alpha) were measured after intravenous sandostatin, propranolol and normal saline. RESULTS: GMBF and PVP were reduced after intravenous sandostatin or propranolol. Sandostatin decreased plasma glucagon, plasma and gastric mucosal NO2-/NO3-, and had no effect on MAP and heart rate of PHG rats as compared with control group of PHG. Propranolol had not these effects, but it might decrease MAP and heart rate. There were no differences of plasma and gastric mucosal 6-Keto-PGF(1alpha) between all PHG groups. CONCLUSION: Sandostatin reduced GMBF of rats with PHG by hindering glucagon, NO, and had no effect on systemic hemodynamics.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Obstetric admissions to the intensive care unit.

OBJECTIVE: To determine whether obstetric admissions to the intensive care unit (ICU) are useful quality-assurance indicators. METHODS: We analyzed retrospectively obstetric ICU admissions at two tertiary care centers from 1991 to 1997. RESULTS: The 131 obstetric admissions represented 0.3% of all deliveries. The majority (78%) of women were admitted to the ICU postpartum. Obstetric hemorrhage (26%) and hypertension (21%) were the two most common reasons for admission. Together with cardiac disease, respiratory disorders, and infection, they accounted for more than 80% of all admissions. Preexisting medical conditions were present in 38% of all admissions. The median Acute Physiology and Chronic Health Evaluation II score was 8.5. The predicted mortality rate for the group was 10.0%, and the actual mortality rate was 2.3%. CONCLUSION: The most common precipitants of ICU admission were obstetric hemorrhage and uncontrolled hypertension. Improved management strategies for these problems may significantly reduce major maternal morbidity.

Adult↗
PubMed1998

Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage activation.

LPS endotoxin-induced macrophage activation is recognized to be important in both nonspecific immunity and endotoxin-induced sepsis when excessive macrophage stimulation occurs. In this study, we showed that reduction of c-Abl in macrophages prevented LPS-induced growth arrest, nitric oxide production and TNF-alpha secretion by ANA-1 macrophages. These cells continued to grow but later underwent apoptosis. Reduction of c-Abl in these cells led to reduced c-Abl kinase activity associated with Ran, which recently has been shown to be an LPS-responsive gene product. Our data suggest that c-Abl tyrosine kinase is one of the intermediates downstream of the initial signal transduction event related to activation of macrophages by LPS.

Animals↗
PubMed1995

Cage size and flight speed of the tobacco hawkmoth Manduca sexta

Flight speeds and behaviors of the sphinx moth Manduca sexta were recorded in chambers of four different sizes (0.57, 8.5, 44 and 447 m3). Mean horizontal speed increased linearly with the cube root of chamber volume from 0.57 m s-1 in the smallest chamber to 3.4 m s-1 in the largest. The maximum horizontal speed observed was 5.3 m s-1 in the largest chamber. Speeds decreased linearly with the logarithm of hawkmoth proximity to the wall. In a tunnel chamber (the third largest), moths often flew in a scalloped-shaped path. At the top of the scallop, they glided for 1&shy;5 wing beats. In the largest chamber, moths could be recorded flying at angles other than horizontal (0 &deg;). At flight angles greater or less than 0 &deg;, mean speed decreased linearly with angle until &plusmn;40 &deg;. At greater angles, speeds remained between 1 and 2 m s-1. Moths also flew closer to the wall at flight angles deviating from the horizontal. An allometric analysis of the flight speeds of insects and birds suggests that M. sexta may be able to fly at 7&shy;10 m s-1. We conclude that chamber size limits the flight speed and modifies the flight behavior of the tobacco hawkmoth.

Journal Article↗
PubMed1995

Continuing risk for hepatitis B virus transmission among Southeast Asian infants in Louisiana.

OBJECTIVE: Implementation and evaluation of a hepatitis B vaccination program for Southeast Asian infants in Louisiana. METHODS: A baseline seroprevalence survey of hepatitis B virus (HBV) infection in US-born Southeast Asian children was conducted in 1991 before the implementation of a vaccination program. Hepatitis B vaccination and postvaccination serologic testing of survey participants 10 years of age and younger was performed. Eighteen months after the hepatitis B vaccine was integrated into infant immunization schedules in July 1993, a vaccination coverage survey was performed. RESULTS: Baseline serologic testing was conducted on 96% of persons from 225 randomly selected households in a Southeast Asian community in Louisiana. Of 676 US-born children, 28 (4.1%) had chronic HBV infection; 61% of children with chronic HBV infection were born to hepatitis B surface antigen (HBsAg)-negative women. Among children born to HBsAg-negative women, the prevalence of chronic HBV infection increased with age, reaching 7.3% for children 13 to 16 years of age. Children born to HBsAg-negative women and living with carriers were 5.4 times more likely to have evidence of HBV infection than were children who did not live with carriers. Before the survey, only one child had received three doses of hepatitis B vaccine. In July 1993, 43% of Southeast Asian infants 9 to 18 months of age born in Louisiana had received three doses of hepatitis B vaccine. Infants who received immunizations from private providers were more likely to be fully vaccinated than were infants who received services from public sector clinics (prevalence ratio, 2.1; 95% confidence interval, 1.4, 3.1). CONCLUSIONS: HBV transmission occurs throughout childhood in US-born Southeast Asian children, and the prevalence of chronic HBV infection approaches that of the country of origin. Few US-born Southeast Asian children have received hepatitis B vaccine. Because of the high rates of early childhood HBV transmission and the high risk of chronic infection in Asian and Pacific Islander communities, prevention efforts should be enhanced to ensure that all Asian and Pacific Islander infants receive hepatitis B vaccine in the first 12 months of life and that older children are vaccinated.

Adolescent↗
PubMed1991

A novel metalloproteinase present in freshly isolated rat glomeruli.

We have utilized [3H] gelatin to document high activity of a metalloproteinase present in freshly isolated rat glomeruli. [3H] gelatin degradation by glomeruli was markedly inhibited by EDTA (10 mM: -89 +/- 2.3%) and o-phenanthroline (2 mM: -72 +/- 0.1%), inhibitors of metalloproteinases. No significant inhibition of [3H]gelatin degradation was observed with inhibitors of serine or cysteine proteinases. Most (greater than 80%) of the glomerular metalloproteinase (GLOMP) activity was associated with the pellet after centrifugation of sonicated glomeruli at 100,000 g for 90 min. The pH optimum for gelatin degradation by sonicated glomeruli was approximately pH 8.5. Sodium dodecyl sulfate substrate (gelatin)-polyacrylamide gel electrophoresis revealed a single major band of EDTA-inhibitable gelatin-degrading activity with a molecular mass of approximately 116-125 kDa. The GLOMP activity was not inhibited by tissue inhibitors of metalloproteinases, did not appear to be latent, and was not activated by organomercurial activators of several latent metalloproteinases. GLOMP activity was increased 3.4-fold after incubation with trypsin (20 micrograms/ml, 25 min, 22 degrees C). These data indicate that GLOMP is distinct from the previously described matrix metalloproteinases, as well as other metalloproteinases present in the kidney, including the gelatinase secreted by cultured mesangial cells, Meprin, and endopeptidase 24.11 (enkephalinase, EC 3.4.24.11).

Animals↗
PubMed1991

AuthorBase: a database of authoring systems software.

A working prototype database of authoring system software was developed as part of a study of authoring software conducted by the National Library of Medicine. The database and development issues ranging from the scope of the database to what information to document are described. The protype demonstrates that records of reasonable integrity can be derived from vendor supplied information as long as users understand the database is only an initial starting point in searching for authoring software and a resource for becoming generally familiar with the technology.

Authorship↗