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Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 883 records · Page 49Linked to original sources
PubMed1996

Biodistribution of cyclic carbonate of ioxilan: a radiopaque particulate macrophage imaging agent.

RATIONALE AND OBJECTIVES: A biodegradable radiopaque particulate contrast agent formulated from cyclic carbonate of ioxilan (IXC), which is a prodrug of nonionic water-solubel contrast ioxilan, recently has been developed. This contrast agent enhances liver attenuation and is cleared from the body as ioxilan. In the current study, we tested whether the biodistribution of IXC particles would be affected by the characteristics of particles. METHODS: IXC nanoparticles (average diameter = 290 nm) and IXC microparticles (average diameter = 1.7 mm) were prepared, characterized, and injected intravenously (i.v.; 50 mg I/kg body weight) into rats. Two sensitive, reproducible analytic methods--inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC)- were used to quantify tissue iodine and ioxilan concentrations. RESULTS: Both IXC nanoparticles and microparticles were taken up in the liver and spleen. The IXC nanoparticles remained in the liver at high concentrations for 6 hr and were slowly cleared. They also gave a high blood iodine concentration in the first 5 min after i.v. injection, suggesting their potential use as a blood-pool imaging agent. Unlike the nanoparticles, the microparticles had a significantly lower uptake by the kidney. CONCLUSION: Because of reduced renal uptake, microparticles are a preferred macrophage imaging agent. Biodegradable radiopaque particles may be used either as blood-pool imaging agents or as macrophage imaging agents depending on their size and distribution characteristics. The ICP-MS and HPLC methods are useful for biodistribution studies of iodinated contrast agents.

Animals↗
PubMed1996

Assessment of tumor cell proliferation using [18F]fluorodeoxyadenosine and[18F]fluoroethyluracil.

This study was to develop radiofluorinated ethyluracil (FEU) and deoxyadenosine analogues (FAD) for noninvasive assessment of tumor proliferative potential by positron emission tomography (PET). 5-(2-Fluoroethyl)uracil ([18F]FEU) was prepared by treating 2,4-dimethoxy-5-(2-hydroxyethyl)pyrimidine with K18F, followed by hydrolysis with HBr. Fluorodeoxyadenosine ([18F]FAD) was prepared by treating a triacetylated analogue of adenosine with K18F. In vitro cell proliferation assay of [18F]-FEU was performed using human peripheral blood mononucleus cells. Tissue distributions were studied in breast tumor-bearing rats at 0.5, 1, 2 and 4 h along with autoradiography at 45 min postinjection. PET imaging studies were conducted in VX-2 tumor-bearing rabbits. In vitro assay indicated that [18F]FEU incorporated into DNA/RNA during cell proliferation. Tumor-to-tissue count density ratios of [18F]FAD and [18F]-FEU increased as a function of time. [18F]FAD had higher tumor-to-nontumor tissue count density ratios than [18F]FEU. Autoradiograms of [18F]FEU and [18F]FAD, and PET images of [18F]FEU, showed that the tumors could be well visualized. The results suggest that [18F]FEU and [18F]FAD have potential use in evaluating tumor cell proliferation by PET.

Animals↗
PubMed1996

Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes.

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) offers safe and effective therapy for certain viral infections and could prove useful in the eradication of tumor cells. Whether or not the infused T cells persist for extended periods, retaining their ability to expand in response to antigenic stimulation, is not known. We now report long-term detection of gene-marked Epstein-Barr virus (EBV)-specific CTLs in immunocompromised patients at risk for the development of EBV lymphoproliferative disease. Infusions of CTLs not only restored cellular immune responses against EBV, but also established populations of CTL precursors that could respond to in vivo or ex vivo challenge with the virus for as long as 18 months. Our findings support wider use of antigen-specific CTLs in adoptive immunotherapy.

Bone Marrow Transplantation↗
PubMed1996

Histological examination of the antlerogenic region of red deer (Cervus elaphus) hummels.

Hummels are antlerless red deer stags. This abnormality has been attributed to poor feeding conditions which result in failure by the deer to grow complete pedicles. Incomplete pedicles lack the potential to develop normal antlers. The histological examinations in this study showed that the rudimentary pedicles (5 mm and 15 mm in height) grown by the two hummels respectively were developed by intramembranous ossification. This is the way that the frontal lateral crests of normal deer are formed, while, in contrast, antlers grow by endochondral ossification. The transition between the ossification types is most important, and occurs during pedicle growth. Therefore, we suggest that the antlerless condition of hummels is due to their failure to initiate true pedicle growth (which has the potential to develop into an antler) because the change from one ossification type to another does not occur. In view of the fact that both hummels were very small in terms of weight (33.7 kg and 51.8 kg, respectively) for their age, it is possible that nutritional cues are necessary for complete pedicle formation. Presumably these cues act synergistically with androgens for the development of the pedicle/antler as a secondary sexual character. It is possible that nutrition controls pedicle initiation through the IGF1 pathway.

Journal Article↗
PubMed1996

RXR-mediated regulation of the alpha-fetoprotein gene through an upstream element.

Retinoic acid (RA) is known to have potent effects on development and differentiation. RA exerts its effects on transcription through two distinct classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), that bind to specific RA-responsive elements (RARE) in target genes. alpha-Fetoprotein (AFP), a hepatocyte differentiation, maturation, and carcinogenesis marker, is transcriptionally upregulated by RA in McA-RH8994 hepatoma cells. Using deletion mapping analysis, we have identified a RARE-like sequence that is located between -2406 and -2378 of the transcription initiation site of the rat AFP gene. Sequence analysis demonstrated that this cis-acting element consists of three direct repeats and one inverted repeat of a GGGTCA-like half-site. The putative RARE can specifically bind to both RXR homodimers and RAR/RXR heterodimers as determined by gel mobility shift assays. A DR1 direct repeat was more efficient than a DR5 direct repeat oligonucleotide in competition for binding of the putative RARE to RXR and RAR/RXR. A mutagenesis study indicated that to have a full-strength induction, all the repeats were required. To further analyze the function of this element in vivo, a reporter gene construct of the putative RARE combined with the thymidine kinase promoter was cotransfected with RAR and RXR expression plasmids in CV1 cells. CAT assays demonstrated that overexpression of RXRalpha conferred the best RA response, consistent with our previous observation that 9-cis-RA is more potent than all-trans-RA for inducing the expression of the AFP gene. In addition, the RXR selective ligand LG100153 alone can stimulate the expression of the AFP gene. Our data suggest that an RXR-mediated pathway exists for modulation of AFP gene expression through a specific element.

Animals↗
PubMed1996

Further evidence that infection is an infrequent cause of first trimester spontaneous abortion.

A previous cohort study found no clinical evidence that infection occurred more often in subjects experiencing pregnancy loss compared with those experiencing successful pregnancy [Simpson et al. (1996) Hum. Reprod., 11, 668-672]. Given these surprising findings, we conducted a similar analysis on another cohort also followed prospectively. Using couples practising natural family planning for conception or contraception, information on clinical evidence of infection was gathered beginning with week 5 of gestation. Information on fever and signs of overt infection was specifically sought by interview and physical examination. Frequencies of urinary, vaginal and other infections in subjects experiencing pregnancy loss were 11.1, 9.5 and 8.7% respectively, not significantly different from rates in subjects having liveborns (10.1, 10.2 and 10.3% respectively). Thus, no association between clinical infection and early pregnancy loss (< or = 16 weeks) was observed. Cohort studies utilizing biologically based assays are awaited because extant data do not provide evidence that clinically evident infections play major roles in first trimester pregnancy losses.

Abortion, Spontaneous↗
PubMed1996

Synthesis and evaluation of water-soluble polyethylene glycol-paclitaxel conjugate as a paclitaxel prodrug.

Water-soluble paclitaxel may cause less side effects and be less costly to administer in comparison to a taxol formulation using a cremophor EL/alcohol vehicle. In this study, polyethylene glycol (PEG; MW 5000) was conjugated to the 2' position of paclitaxel through a spacer succinyl group. PEG-paclitaxel as a non-ionic paclitaxel prodrug was highly water soluble (> 20 mg equiv. paclitaxel/ml). The release of paclitaxel from phosphate-buffered solution was pH dependent. The half-life of PEG-paclitaxel was 7.6, 54 and 311 min at pH 9.0, 7.4 and 6.0, respectively. PEG-paclitaxel inhibited the growth of B16 melanoma cells to an extent similar to that of paclitaxel. In MCA-4 mammary tumor-bearing mice, a single dose of PEG-paclitaxel (40 mg equiv. paclitaxel/kg body weight) significantly delayed tumor growth. The average number of days for the tumor to reach 12 from 8 mm in diameter increased from 6.5 days for control animals to 8.5 days for PEG-paclitaxel-treated animals and 9.4 days for paclitaxel-treated animals. These studies demonstrated that PEG may be used as an effective solubilizing carrier for paclitaxel.

Animals↗
PubMed1996

Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a preliminary report.

In order to investigate the prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with and without comorbid substance use disorder, a total of 40 patients, from an outpatient neuropsychiatric clinic in Princeton, New Jersey, were genotyped for presence or absence of the Taq I DRD2 A1 allele. The primary inclusion criterion for 40 obese subjects was a body mass index (BMI) equal to or over 25 (uncharacterized); 11 obese subjects had severe substance use disorder; 20 controls had a BMI below 25; and, 33 substance use disorder (less severe) patients had a BMI below 25. The data were statistically compared with three different sets of controls divided into three separate groups (Group I, n = 20; Group II, n = 286; Group III, n = 714). They differed according to screening criteria (drug, alcohol, nicotine abuse/dependence, BMI below 25 and other related behaviours including parental history of alcoholism or drug abuse and DSM IV, Axis I and Axis II diagnoses). Groups II and III were population controls derived from the literature. The prevalence of the Taq I A1D2 dopamine receptor (DRD2) alleles was determined in 40 Caucasian obese females and males. In this sample with a mean BMI of 32.35 +/- 1.02, the A1 allele of the DRD2 gene was present in 52.5% of these obese subjects. Furthermore, we found that in the 23 obese subjects possessing comorbid substance use disorder, the prevalence of the DRD2 A1 allele significantly increased compared to the 17 obese subjects without comorbid substance use disorder. The DRD2 A1 allele was present in 73.9% of the obese subjects with comorbid substance use disorder compared to 23.5% in obese subjects without comorbid substance use disorder. Moreover, when we assessed severity of substance usage (alcoholism, cocaine dependence, etc.) increasing severity of drug use increased the prevalence of the Taq I DRD2 A1 allele; where 66.67% (8/12) of less severe probands possessed the A1 allele compared to 82% (9/11) of the most severe cases. Linear trend analyses showed that increasing use of drugs was positively and significantly associated with A1 allelic classification (p < 0.00001). These preliminary data suggest that the presence of the DRD2 A1 allele confirms increased risk not only for obesity, but also for other related addictive behaviours (previously referred to as the Reward Deficiency Syndrome) and that a BMI over 25 by itself (without characterization of macroselection or comorbid substance use disorders) is not a sufficient criterion for association with the DRD2 A1 allele.

Adult↗
PubMed1996

Lipid vs protein theories of alcohol action in the nervous system.

There has been a long-standing debate concerning whether alcohols produce their effects in the central nervous system (CNS) by acting on lipids or proteins. Lipid theories postulate that alcohols act via some perturbation of the membrane lipids of CNS neurons, whereas protein theories propose that alcohols act by interacting with a neuronal protein site. Although the primary site of action differs in the two theories, both theories postulate that the CNS effects of alcohols ultimately result from alterations in protein function. This review discusses lipid and protein theories of alcohol action and the evidence supporting these theories. In addition, the effects of alcohols on the function of neurotransmitter-gated ion channels are discussed, as several types of these receptor-ion channels have been found to be sensitive to the actions of alcohols, and recent studies on those actions have yielded new insights into the question of whether the primary action of alcohols involves lipids or proteins.

Alcohol Drinking↗
PubMed1996

Primary malignant melanoma of the sinonasal cavity: MR imaging evaluation.

To evaluate the magnetic resonance (MR) imaging characteristics of primary malignant melanoma of the sinonasal cavity, T1- and T2-weighted MR images of 12 patients with primary sinonasal melanoma were retrospectively reviewed. Gadolinium-enhanced imaging was performed in seven cases. The MR images were compared with histopathologic results. There were seven melanotic melanomas and five amelanotic melanomas; hemorrhage was present in three melanotic and two amelanotic melanomas. The seven melanotic melanomas were hyperintense to gray matter on T1-weighted images (whether hemorrhage was present or not), consistent with the paramagnetic effect of melanin. Four of the five amelanotic melanomas had intermediate signal intensity on T1-weighted images; one was not detected. On T2-weighted images, all of the melanomas detected had intermediate though variable signal intensity compared with that of gray matter. On gadolinium-enhanced images, all cases demonstrated mild to moderate enhancement. The signal intensity of sinonasal melanoma appears to vary according to the histopathologic components of the tumor. High signal intensity within the lesion on T1-weighted images suggests the presence of melanin.

Aged↗
PubMed1996

Reperfusion injury on cardiac myocytes after simulated ischemia.

The extent of cardiac injury incurred during reperfusion as opposed to that occurring during ischemia is unclear. This study tested the hypothesis that simulated ischemia followed by simulated reperfusion causes significant "reperfusion injury" in isolated chick cardiomyocytes. Cells were exposed to hypoxia, hypercarbic acidosis, hyperkalemia, and substrate deprivation for 1 h followed by 3 h of reperfusion. Irreversible cell membrane injury, measured by propidium iodide uptake, increased from 4% of cells at the end of ischemia to 73% after reperfusion; death occurred in only 17% of cells kept ischemic for 4 h. Lactate dehydrogenase release was consistent with these changes. Lengthening ischemia from 30 to 90 min increased cell injury as expected, but of the total cell death, > 90% occurred during reperfusion. "Chemical hypoxia" composed of cyanide (2.5 mM) plus 2-deoxyglucose augmented injury before reperfusion compared with simulated ischemia. Inhibition of oxygen radical generation by use of metal chelator 1,10-phenanthroline reduced cell death from 73% to 40% after reperfusion (P = 0.001). We conclude that simulated reperfusion significantly augments the cellular membrane damage elicited by simulated ischemia in isolated cardiomyocytes devoid of other factors and suggest that reactive oxygen species, perhaps from the mitochondria, participate in this injury.

Animals↗
PubMed1996

Oxidant stress stimulates mucin secretion and PLC in airway epithelium via a nitric oxide-dependent mechanism.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide variety of respiratory diseases. We investigated mechanisms of ROS-induced mucin secretion by guinea pig tracheal epithelial (GPTE) cells in primary culture, and ROS-induced activation of the second messenger-producing enzyme phospholipase C (PLC), in GPTE cells and in a virally transformed cell line (BEAS-2B) derived from human bronchial epithelium. Mucin secretion was measured by a monoclonal antibody-based enzyme-linked immunosorbent assay, and PLC activation was assessed by anion exchange chromatography. ROS generated enzymatically by xanthine oxidase (XO, 500 microM) in the presence of purine (500 microM) enhanced release of mucin by GPTE cells and activated PLC in GPTE and BEAS cells. Hypersecretion of mucin and activation of PLC in response to purine + XO appeared to occur via an intracellular pathway(s) dependent on endogenously produced nitric oxide and possibly intracellularly generated oxidants. Both responses could be blocked or attenuated by preincubation of the cells with NG-monomethyl-L-arginine, an inhibitor of the enzyme nitric oxide synthase, or with dimethylthiourea, a compound that can react with a variety of intracellular oxidant species. Reactive nitrogen species generated chemically also stimulated secretion of mucin and activated PLC via a mechanism dependent (at least in part) on intracellular oxidant-mediated process(es). The results suggest that intracellularly generated radical species of nitrogen and oxygen may be important modulators of the response of airway epithelial cells to external oxidant stress.

Animals↗
PubMed1996

Proton potentiation of ATP-gated ion channel responses to ATP and Zn2+ in rat nodose ganglion neurons.

1. The modulation by protons of ATP-gated ion channel responses to ATP and Zn2+ was studied in freshly isolated rat nodose ganglion neurons using the whole cell patch-clamp technique. 2. Reduced external pH enhanced, whereas elevated external pH suppressed, current activated by 10 microM ATP. The pH producing the half-maximal effect (EC50) at this ATP concentration was 7.1. 3. Acidification shifted the ATP concentration-response curve to the left, decreasing the EC50 for ATP, and alkalinization shifted the ATP concentration-response curve to the right, increasing the EC50 for ATP. Fitting the data to a single-site pH model yielded an apparent pKa of the site on the ATP-gated ion channel of 7.6. Between pH 6.8 and 7.8, a change of 0.1 pH unit was calculated to change the ATP EC50 by 4.03 microM. Changing pH did not alter the maximal response to ATP. 4. The potentiating effect of protons appeared to be due to a direct action on the ATP-gated channel, as it could not be explained by an increase in the concentration of one or more species of ATP. 5. Lowering pH also increased the potency of Zn2+ for enhancement of ATP-activated current without altering its maximal response. Changing the pH from 7.3 to 6.8 changed the Zn2+ EC50 from 12 to 1.7 microM. 6. The potentiation of ATP-activated current by protons could not be attributed solely to an increase in the affinity of the receptor for Zn2+, as the Zn2+ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine did not alter the effect of protons. 7. Protons and Zn2+ do not appear to act at the same site on ATP-gated channels, as responses to maximally effective concentrations of Zn2+ were enhanced further by protons and vice versa. 8. These results suggest that protons regulate the function of P2X purinoceptors in rat nodose ganglion neurons by modulating the affinity of the binding sites for ATP and Zn2+ on these receptor channels.

Adenosine Triphosphate↗
PubMed1996

Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization.

We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations.

Adult↗
PubMed1996

Factors associated with multiple hospitalizations of patients with borderline personality disorder.

OBJECTIVE: The study sought to identify aspects of borderline personality disorder and comorbid axis I conditions associated with multiple hospitalizations in a sample of patients with borderline personality disorder. METHODS: Data were collected as part of a larger study of treatment course of inpatients with this disorder. Predictors of multiple hospitalization from three domains were considered: demographic characteristics, criteria of borderline personality disorder, and comorbid axis I pathology. A sequential model-building strategy was used, with each domain considered separately and result combined into an overall regression model of factors related to multiple hospitalization. RESULTS: Three factors were related to frequency of hospitalization: anorexia, psychotic symptoms, and suicidality. Other variables that are often assumed to be related to hospitalization, such as depression, did not emerge as significant predictors. CONCLUSIONS: Clinicians should intervene early to address the emergence of certain axis I conditions among patients with borderline personality disorder. Increased expenditure of outpatient resources may prevent hospitalization when these conditions are present.

Adolescent↗
PubMed1996

Variation of intrarenal angiotensin II and angiotensin II receptors by acute renal ischemia in the aged rat.

The properties of Ang II receptors in the aged kidney and their changes after acute renal ischemia are rarely known. The aim of this study was to examine the expression of Ang II receptor mRNA and characteristics of Ang II receptors in the aged kidney and to compare different responsiveness to 45 min of acute renal ischemia in young (3-4 months) and aged (23-24 months) rats. In the normal condition, AT1 mRNA expression was much lower in the aged than that in the young rats. Maximal binding (Bmax) was also lower in the aged (1315 +/- 48 vs. 2035 +/- 257 fmol/mg, p < 0.05). The dissociation constant (KD) of glomerular Ang II receptors, however, was significantly lower in the aged rats compared to the young (6.8 +/- 1.6 vs. 17.4 +/- 2.5 nM). After acute ischemia, the expression of AT1 mRNA decreased in the young rats but increased in the aged rats. Interestingly, Bmax of glomerular Ang II receptors was significantly increased in the aged ischemic rats (1852 +/- 94 vs. 1315 +/- 48 fmol/mg) with unchanged KD. These results show that: (a) the AT1 mRNA expression and the Ang II receptor binding site are decreased with the aging process in the rat kidney; (b) the acute renal ischemia effect on different age groups has a greatly discrepant pattern in respect of Ang II receptor modulation, which may provide a potential therapeutic future for the receptor antagonists in acute renal ischemia in the aged.

Acute Disease↗
PubMed1996

Adoptive immunotherapy for Epstein-Barr virus-related lymphoma.

Epstein-Barr virus (EBV) causes opportunistic B cell lymphomas in patients whose cellular immunity is compromised. We have been investigating whether infusions of donor-derived, EBV-specific cytotoxic T cells can prevent and/or treat EBV-related lymphoproliferative disease in children receiving T cell-depleted bone marrow from HLA-matched, unrelated or HLA-mismatched, related donors. In this review, we discuss the rationale for this therapeutic approach, describe our experiences with the regimen thus far, and consider some future directions in immunotherapy.

Child↗