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Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 1,243 records · Page 69Linked to original sources
PubMedDate not supplied

Poly(ethylene glycol)-conjugated anti-EGF receptor antibody C225 with radiometal chelator attached to the termini of polymer chains.

Several biological barriers, including significant liver uptake, limit the clinical application of radiolabeled antibodies in radioimmunoscintigraphy. Here, a general approach is described for radiolabeling of monoclonal antibodies conjugated with poly(ethylene glycol) (PEG). This strategy is demonstrated with C225, a monoclonal antibody directed against epidermal growth factor (EGF) receptor. We synthesized a heterofunctional PEG with one end attached to a radiometal chelator, diethylenetriaminepentaacetic acid (DTPA), and the other end to a protected thiol group, S-acetylthioacetate. After a deprotection step, the resulting DTPA-PEG-SH was conjugated to maleimide-activated C225 to yield DTPA-PEG-C225 conjugate. Characterization of DTPA-PEG-C225 with immunoprecipitation and Western blot analysis revealed that the conjugate was biologically active in binding to the EGF receptor in A431 cells. Competitive EGF receptor binding assay in MDA-MB-468 cells showed that DTPA-PEG-C225, with up to 60% of the amino groups in C225 substituted, retained 66% of C225's binding affinity. Moreover, DTPA-PEG-C225 with increasing degrees of NH(2) substitution from 20% to 70% retained the activity of C225 to induce apoptosis in DiFi cells. More importantly, DTPA-PEG-C225 demonstrated less nonspecific interaction than DTPA-C225. Pharmacokinetic analysis using (111)In-labeled compounds revealed narrower steady-state distribution of (111)In-DTPA-PEG-C225 than (111)In-DTPA-C225, probably due to reduced nonspecific binding of PEG-modified antibody to tissues. The terminal half-life (t(1/2,)(gamma)) of (111)In-DTPA-PEG-C225, 21.1 h, was shorter than that of (111)In-DTPA-C225, 52.9 h. These data suggest that (111)In-DTPA-PEG-C225 may provide better imaging characteristics than (111)In-DTPA-C225, and that using PEG as a linker between the monoclonal antibody and DTPA may be a promising strategy in optimizing the imaging characteristics of immunoscintigraphic agents.

Antibodies, Monoclonal↗
PubMedDate not supplied

Optimization of conditions for bacteriocin extraction in PEG/salt aqueous two-phase systems using statistical experimental designs.

The bacteriocin nisin was extracted in PEG/salt aqueous two-phase systems (ATPS) using the property that the systems can extract hydrophobic proteins. The concentrations of the phase-forming components, PEG 4000 and Na(2)SO(4), were optimized for nisin recovery by means of statistical experimental designs, and it was found that they strongly influenced nisin recovery. The optimal composition of ATPS was found to be 15.99% (w/w) PEG 4000 and 15.85% (w/w) Na(2)SO(4) (pH 2), and the optimal ATPS allowed an 11.60% increase of nisin recovery compared to the standard method of nisin assay.

Nisin↗
PubMedDate not supplied

Effects of timing of conception on birth weight and preterm delivery of natural family planning users.

OBJECTIVE: Various birth defects and untoward perinatal outcomes have been claimed to be associated with pregnancies conceived by gametes aged in vivo before fertilization. Thus, these outcomes were systematically assessed in pregnancies occurring in natural family planning (NFP) users. Our international multicenter cohort study of NFP pregnancies (n = 877) is by far the largest systematic study designed to assess pregnancy outcome and is of sufficient power to allow us to address the concern of low birth weight (< 2500 g) and preterm delivery (< 37 weeks gestation). STUDY DESIGN: In addition to gathering baseline medical data, evaluation was performed at 16 weeks, 32 weeks and at term. Data were collected in a systematic cohort fashion, verified by the five collaborating international recruiting centers, and analyzed by investigators in the US. Most recruiting center principal investigators are obstetrician-gynecologists and, if not, have integral relationships with such specialists. Standard criteria could thus be applied within and among centers. In our cohort, birth weight was recorded accurately at delivery. Almost all of the deliveries occurred in hospitals; thus, data should be quite reliable. Neonatal examination for anomalies was usually conducted immediately after delivery, when birth weight was recorded. RESULTS: Analysis of risk factors for low birth weight and preterm delivery showed that this population had a low risk profile. Low birth weight infants (< 2500 g) and preterm deliveries were increased among women with a history of either prior low birth weight or preeclampsia in the index pregnancy. However, mean birth weight was unaffected by the timing of conception vis à vis ovulation or pregnancy history. Mean birth weight for the 877 singleton NFP pregnancies was 3349.6 g. The risk of preterm delivery was increased among older women who drank alcohol, but there were no significant effects of timing of conception vis à vis ovulation on preterm delivery. Results held when analysis was stratified according to whether NFP was being used for contraception or to achieve pregnancy. CONCLUSIONS: Our data do not appear to show striking differences between 877 NFP pregnancies and the general obstetric population. The timing of conception vis à vis ovulation does not exert significant effects on the birth weight or preterm delivery of resulting pregnancies, a reassuring finding for NFP users.

Birth Weight↗
PubMedDate not supplied

Pregnancy outcome in natural family planning users: cohort and case-control studies evaluating safety.

Conceptions involving aging gametes are of relevance to natural family planning (NFP) because women using NFP to avoid pregnancy abstain from intercourse during the fertile time of the cycle. To help verify the safety of pregnancies occurring among NFP practitioners, our group has, since 1986, conducted a large cohort study involving six experienced NFP centers. Timing of conception was determined from NFP charts, in which women recorded days on which intercourse occurred. The number of days from the most probable conception intercourse to probable day of ovulation was first determined, and used as an estimate of the time gametes remained in the genital tract before fertilization. Several studies have already been completed, cohort as well as case-control in nature.

Abortion, Spontaneous↗
PubMedDate not supplied

Pregnancy complications in natural family planning users.

A multicenter cohort study was designed to assess pregnancy outcome among natural family planning (NFP) users, and provide the opportunity to address complications in NFP users by planning status and by timing of conception with respect to day of ovulation. There were 877 singleton births in this sample. Complications evaluated were abnormal vaginal bleeding, urinary tract infection, vaginal infection, hypertension of pregnancy, proteinuria, glycosuria, and anemia. There was no significant difference in the mean age, number of prenatal visits or birth weight among optimally and non-optimally timed pregnancies or for planned and unplanned pregnancies. There were higher incidences of "parity 2 or more" and current smokers in the non-optimally timed pregnancies and lower incidences of prior pregnancy loss and "currently employed" in the non-optimally timed pregnancies. There was little difference in pregnancy complications with respect to pregnancy timing, with the exception of a significant increased risk of vaginal bleeding late in pregnancy among non-optimally timed conceptions (11.5%) compared to optimally timed pregnancies (5.2%, RR = 2.2, 95% CI 1.3-3.7). More differences were observed in pregnancy complication rates by planning status. Unplanned pregnancies were associated with significantly more late pregnancy bleeding, vaginal infections, proteinuria, glycosuria and medication use than planned pregnancies. Unplanned pregnancies had lower incidences of maternal anemia. Complications of pregnancy were low in this NFP population, irrespective of planned versus unplanned status. Women with planned pregnancies had even fewer complications during pregnancy than women with unplanned conceptions, suggesting that women using NFP to plan their reproduction may be at particularly low risk.

Cohort Studies↗
PubMedDate not supplied

The dynamic distribution of fluoro-gold and its interrelation with neural nitric oxide synthase following intracerebroventricular injection into rat brain.

We mapped the dynamic distribution of fluoro-gold (FG) within rat brain following intracerebroventricular (icv) injection into the lateral ventricle and observed its interrelation with neural nitric oxide synthase (nNOS) using FG fluorescent microphotography combined with nNOS immunohistochemistry. We also detected the amount of icv administered FG entering the peripheral circulation using a fluorescence microplate assay. The degree of periventricular penetration of FG was significantly increased over time. At 2 min after icv injection, FG primarily labeled the choroid plexus in the lateral and third ventricles, with limited penetration into the ependyma and the subependyma of the same ventricles. Some FG/nNOS-double labeled cerebrospinal fluid-contacting neurons were observed in these ventricles as well. At 15 and 30 min, FG penetrated mainly into forebrain ventricular organs and parenchymal structures. Many FG/nNOS double labeled neurons were found at each of these sites. In addition, at 30 min intense FG labeling was found in the hypophysis, while limited periventricular penetration of FG was detected in the hindbrain circumventricular areas. In the peripheral circulation, a low concentration of FG was detected 2 min after icv injection. The concentration increased slowly, peaked at 20 min, then gradually decreased until the end of the experiment at 30 min. These findings indicate that dynamic penetration of icv administrated agents into the periventricular tissues and peripheral circulation should be considered when designing icv experiments.

Animals↗
PubMedDate not supplied

Intracranial germ cell tumors in children with and without Down syndrome.

PURPOSE: Two Chinese children with Down syndrome affected by intracranial germ cell tumors are described. Because they represent two of eight affected patients in the current series from 1990 to 1996, it is postulated that such occurrence may be more than a coincidental event. PATIENTS AND METHODS: Two children with Down syndrome developed germ cell tumors in atypical intracranial sites that affected basal ganglion and cerebellum. The pathology showed germinoma and yolk sac tumor, respectively. These were treated by radical surgical resection and chemotherapy with cisplatin, etoposide, and bleomycin, but without radiotherapy. RESULTS: One patient survived 3 years without radiologic evidence of tumor. The other died from infective complications caused by severe myelosuppression after chemotherapy. CONCLUSIONS: Subtle neurologic manifestations in developmentally handicapped patients with intracranial space-occupying lesions could result in delayed diagnosis. Children with Down syndrome suffering from brain tumors may have a higher chance for germ cell tumors. Assay for alpha-fetoprotein and beta-human chorionic gonadotrophin could hasten diagnosis in some cases. This observation and review of literature suggest an increased risk of developing intracranial germ cell tumors in subjects with Down syndrome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Molecular characterization of a sarcoplasmic-endoplasmic reticulum Ca+2 ATPase gene from Trichomonas vaginalis.

DNA fragments homologous to P-type cation translocating ATPase genes were identified in Trichomonas vaginalis by polymerase chain reaction (PCR) amplification. The genomic locus corresponding to one PCR fragment, TVCA1, contains a 3,055 base-pair open reading frame encoding a 108,162 dalton protein composed of 981 amino acids. TVCA1 lacks introns, is present in a single copy, and is expressed as a 3.1 kb transcript with short 5' and 3' untranslated regions. Separate primer extension experiments map the 5' end of the TVCA1 transcript to 12 and 16 nucleotide bases (nt) upstream of the methionine initiation codon. The message polyadenylation site is located 62 nt downstream of the protein termination codon at a CA dinucleotide. The TVCA1 protein sequence shares 57-58% similarity with rabbit, schistosome, trypanosome and malarial sarcoplasmic-endoplasmic reticulum calcium (SERCA) pumps, and significantly lower similarity with plasma membrane calcium pumps and cation translocating ATPases of other ion specificities. Structural and functional domains identified in P-type ATPases as well as 61/68 residues specifically implicated in SERCA pump activity are conserved in TVCA1. However, TVCA1 lacks binding sites for phospholamban regulation, thapsigargin inhibition and the calmodulin dependent protein kinase site phosphorylation present in other SERCA pumps.

Amino Acid Sequence↗
PubMedDate not supplied

Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy.

Diabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by approximately 3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.

Antigens, CD↗
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Analysis of rt-PA infusion in tunnelled dialysis catheters.

Urokinase and streptokinase are commonly used thrombolytic agents for obstructed central venous catheters. Although proven to be efficacious, these agents have the potential to induce fibrin breakdown and streptokinase cannot be used repeatedly due to its allergenic nature. Documented evidence suggests that urokinase is safe and effective (> 70% efficacy for catheter installation) however further evidence points to tissue-type plasminogen activator (rt-PA) achieving as much as 98% success. This study reports on the safety and efficacy of alternative catheter thrombolysis, namely rt-PA and evaluates the efficacy of rt-PA. 20 patients required 57 infusions in 38 lumens between 01/01/02 to 01/09/03. For completely blocked lines rt-PA was infused at 2 mg/hr for 4 hours achieving 85% success rate. For inadequate flow (< 250 mls/min) rt-PA was infused at 1 mg/hr for 4 hours achieving 88% success rate.

Algorithms↗
PubMedDate not supplied

Cell-killing by paclitaxel in a metastatic murine melanoma cell line is mediated by extensive telomere erosion with no decrease in telomerase activity.

The purpose of this study was to investigate and compare the effects of paclitaxel and its water-soluble conjugates (sodium-pentetic acid-paclitaxel; polyethylene glycol-paclitaxel, and poly[L-glutamic acid]-paclitaxel) on chromosome morphology and induction of apoptosis in a metastatic murine melanoma cell line (K1735 clone X-21). For this, murine melanoma cells were treated continuously for 72 h with three concentrations (1.2 microM, 2.4 microM, and 4.8 microM) of each of paclitaxel, and conjugates. Another set of cells were pulse-treated at 2.4 microM, 4.8 microM and 9.6 microM concentrations of each of these drugs for 4 h and the recovered cells were examined after 72 h. Control cultures received only the solvents (dimethyl sulfoxide or water). Our results showed a significant increase in the frequencies of telomeric associations, chromosome aberrations, polyploidization, distorted and disintegrated chromosome morphology, and reduced telomeric signal intensity by fluorescence in situ hybridization, in treated cultures as compared to the controls. However, we detected no change in telomerase activity. In addition, the majority of interphase nuclei in treated cells showed apoptotic bodies, with chromatin condensation. These in vitro results suggest that cell death induced by paclitaxel and its water-soluble conjugates is due to the loss of telomeric repeats, as shown by reduced signal flourescence and increased telomeric associations.

Animals↗
PubMedDate not supplied

Involvement of protein-DNA interaction in adeno-associated virus Rep78-mediated inhibition of HIV-1.

OBJECTIVE: It has been well documented by several laboratories that adeno-associated virus (AAV) is able to inhibit HIV-1 replication and gene expression. This effect has been mapped to the AAV-encoded Rep78 protein. However, the mechanism by which Rep78 is able to inhibit HIV-1 is unclear. As Rep78 is a DNA binding transcription factor, the objective of this study was to investigate where Rep78 might bind within the HIV-1 long terminal repeat (LTR) sequences and to judge the importance of this protein-DNA interaction. STUDY DESIGN/METHODS: Rep78's binding to HIV-LTR DNA was analyzed by electrophoretic mobility shift assay (EMSA). The importance of this protein-DNA interaction was analyzed using a Rep78 mutant defective for binding HIV-LTR DNA in an assay for monitoring gene expression (chloramphenicol acetyltransferase [CAT] assay). RESULTS: The preferred site for Rep78 binding was found to be adjacent to the HIV-LTR TATA box, within nt -54 to -34 relative to the site of transcription initiation. Furthermore, a Rep78 mutant with substitutions at amino acid residues 64 and 65 which was found defective for binding HIV-LTR DNA, was also found to be defective for inhibition of tat transactivated HIV-LTR gene expression. CONCLUSION: These data strongly suggest that Rep78's DNA binding ability is important for its mechanism of inhibition. Furthermore, the TATA box region of the HIV-LTR, to which Rep78 preferentially binds, is a likely target through which the inhibition takes place.

DNA, Viral↗
PubMedDate not supplied

Somatic mutation and homozygous deletion of PTEN/MMAC1 gene of 10q23 in renal cell carcinoma.

We studied chromosome 10q loss of heterozygosity and PTEN/MMAC1 gene inactivation in renal cell carcinoma (RCC). Fifty-four cases of RCCs were analysed by three 10q RFLP markers. Forty one of them were heterozygous for at least one of the markers, of which fourteen showed LOH (34%). Six tumors which showed 10q deletion for RFLP markers and six randomly selected tumors without RFLP LOH were included in an extended study of 10q by eight microsatellite markers. Eight of these cases showed LOH with two smallest deleted regions (SRO) at 10q23 delineated by markers D10S541 and D10S579 while the other distal SRO is between markers D10S587 and D10S212 at 10q25-26. The five tumors with LOH covering 10q23 were selected for mutation analysis of PTEN/MMAC1 gene. One tumor without LOH of 10q23 was selected as a control. Using direct sequencing of nine exons, we found three different base pair changes in three tumors with LOH. Nine RCC cell lines were analysed for PTEN/MMAC1 gene inactivation. One homozygous deletion was detected in the cell line UOK147. No expression of PTEN/MMAC1 gene was detect by RT-PCR in the cell line UOK 147.

Base Sequence↗
PubMedDate not supplied

Important factors for use of hormone replacement therapy: a population-based study of Swedish women. The Women's Health in Lund Area (WHILA) Study.

OBJECTIVE: The aim of this study was to delineate the use of hormone replacement therapy (HRT) among women who were born between December 2, 1935, and December 1, 1945, and living in the Lund area of southern Sweden and to analyze factors that contribute to the acceptance and continuation of HRT. METHODS: All women received a generic questionnaire pertaining to demographic background, lifestyle, health behavior, and climacteric symptoms and underwent a personal interview. An interim analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the women who were using HRT (n = 1,875). This hormone questionnaire covered, for example, menopausal status, complaints, and alterations in and efficacy of HRT use, as well as the reasons for discontinuing HRT use. RESULTS: A total of 1,415 (76%) women answered the hormone questionnaire. Forty-eight percent were HRT ever users, and 32% were current users. Mean duration of HRT use was 47 months. The most common incentives for HRT use were alleviation of menopausal symptoms (72%) and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty-seven percent of HRT users reported that they had changed regimens at least once. HRT users had higher education, full-time work, and a higher consumption of alcohol but less consumption of cigarettes. They reported higher frequencies of climacteric symptoms, past histories of premenstrual syndrome, use of oral contraceptives, and hysterectomy. They also had a higher consumption of healthcare resources. A total of 177 women withdrew from therapy. The most common reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding, breast tenderness, and emotional problems. Compared with current users, past users had less positive as well as fewer negative effects of HRT. Several variables contributed to compliance, including education, full-time work, regular exercise, low frequency of persistent climacteric symptoms, and alteration of regimens. CONCLUSION: Education, working conditions, lifestyle, interest in prevention, and severity of the climacteric symptoms are determinants for both acceptance of and compliance with HRT.

Cardiovascular Diseases↗
PubMedDate not supplied

Hepatic chemoembolization: clinical and experimental correlation.

Chemoembolization has become the preferred treatment for patients with inoperable, hypervascular hepatic malignancies in the Far East, but controversial elsewhere. In vivo microscopy in addition to other experimental procedures are used in this presentation to better understand the mechanisms involved in chemoembolization. In chemoembolization Lipiodol acts as a contrast material, a vehicle for chemotherapy and an embolic agent. Although not optimal, Lipiodol injected into the hepatic artery, traverses the peribiliary plexus to the portal veins resulting in a dual embolization. Chemoembolization creates ischemia, slows arterial flow and increases the contact time between the infusate and the neoplasms, increasing the tumor cell kill. However, the vascular occlusion also produces infarction and fibrosis compounding the already existing cirrhosis frequently associated with hepatocellular carcinoma. Lipiodol/ethanol (3:1) injected into the segmental or lobar hepatic artery supplying the neoplasm also gains access to the associated portal venous branches causing focal ablation. This preoperative approach is easier to perform than direct portal vein occlusion, with less parenchymal damage and comparable hypertrophy of the remnant liver frequently necessary for adequate hepatic function following resection. Polymer-drug conjugates, e.g. PG-TXL, have considerable potential for intra-arterial delivery especially with the dramatic increase in concentration of the drug in the tumor and its efficacy. Using in vivo microscopy especially with green fluorescent protein (GFP) gene as an efficient and non-toxic tumor cell marker, the events leading to hepatic metastases can be documented which will serve to better evaluate these varied techniques of chemoembolization.

Animals↗
PubMedDate not supplied

Corticosteroids in polymyalgia rheumatica--a review of different treatment schedules.

Low dose oral steroids (prednisolone 10-15 mg daily) are currently advocated for the treatment of uncomplicated PMR and the dose should be carefully adjusted in relation to disease activity. Intramuscular methylprednisolone has been shown to have a similar remission rate to oral steroids and a better side effect profile with respect to fracture rate and weight gain. Prophylaxis for osteoporosis at least with calcium and vitamin D should be initiated at the start of steroid therapy.

Drug Administration Schedule↗
PubMedDate not supplied

Expression of multidrug resistance-related markers in gastric cancer.

BACKGROUND: To detect the expression of glutathione S-transferase Pi(GST-pi), multidrug resistance-associated protein (MRP), lung-resistance protein(LRP), multidrug resistance gene1 (MDR1) and MGr1 antigen(MGr1-Ag) in the patients with primary gastric cancer and without any prior chemotherapy and to evaluate the correlations between them. PATIENTS AND METHODS: The expression of GST-pi, MRP, LRP and MDR1 in cancer tissue and the adjacent non-cancerous tissue from 50 patients was examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of MGr1-Ag in these tissues was also examined by immunohistochemistry. RESULTS: The positive rate of GST-pi mRNA, MRP mRNA, LRP mRNA, MDR1mRNA and MGr1-Ag in gastric cancer tissue was 36.00%, 12.00%, 10.00%, 10.00% and 18.00% respectively. The overall positive rate of their expression was 58.00%. Clinicopathological factors were not significantly related to their expression. No significant correlation was observed between these markers. CONCLUSION: These MDR markers are differently over-expressed and no coexpression exists in gastric cancer. MGr1-Ag was a novel MDR protein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗