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At least 1,135 records · Page 63Linked to original sources
PubMed2003

Enhanced expression of uterine stathmin during the process of implantation and decidualization in rats.

We used the library subtraction technique to identify genes specifically expressed in the rat uterus during early pregnancy. One such gene was that for stathmin, a factor that is associated with tubulin binding and the destabilization of microtubules. Stathmin was expressed at higher levels in implantation sites than in interimplantation sites on d 6 and 7 of pregnancy; the levels on d 6 and 7 were higher in implantation sites than in the entire uterus on d 3-5 of pregnancy or in nonpregnant uteri. Intense expression of stathmin mRNA was primarily limited to the subluminal stromal cells at the implantation site. Expression was also detected in the decidual zones and was accentuated during the period of decidualization (d 7-12). In the delayed implantation pregnant rat model, uterine stathmin expression was low, but increased after implantation induced by administration of 17beta-estradiol to the progesterone-primed animal. Further, decidualization in the pseudopregnant rat, induced by intrauterine infusion of oil, enhanced stathmin expression. Stathmin expression clearly increases in the uterus when stimulated by embryo implantation and decidualization and may play a role in the early stages of pregnancy.

Animals↗
PubMed2002

Identification of neuropeptide W as the endogenous ligand for orphan G-protein-coupled receptors GPR7 and GPR8.

The structurally related orphan G-protein-coupled receptors GPR7 and GPR8 are expressed in the central nervous system, and their ligands have not been identified. Here, we report the identification of the endogenous ligand for both of these receptors. We purified the peptide ligand from porcine hypothalamus using stable Chinese hamster ovary cell lines expressing human GPR8 and cloned the cDNA encoding its precursor protein. The cDNA encodes two forms of the peptide ligand with lengths of 23 and 30 amino acid residues as mature peptides. We designated the two ligands neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). The amino acid sequence of NPW23 is completely identical to that of the N-terminal 23 residues of NPW30. Synthetic NPW23 and NPW30 activated and bound to both GPR7 and GPR8 at similar effective doses. Intracerebroventricular administration of NPW23 in rats increased food intake and stimulated prolactin release. These findings indicate that neuropeptide W is the endogenous ligand for both GPR7 and GPR8 and acts as a mediator of the central control of feeding and the neuroendocrine system.

Amino Acid Sequence↗
PubMed1995

Isolation and characterization of a new cDNA clone belonging to the cytochrome P450 2C gene subfamily in hamsters.

Cytochrome P450s are heme-containing proteins which evolved from an ancestral gene to form a large superfamily of enzymes. We previously isolated three distinct CYP2C cDNAs, namely CYP2C25, 2C26, and 2C27, from liver cDNA libraries of male and female Syrian hamsters. In the present study, we isolated another cDNA clone, assigned as CYP2C28, from the same male cDNA library. This cDNA consisted of 1556 nucleotides and encoded a polypeptide of 490 amino acids. CYP2C28 showed relatively low identities to other hamster CYP2C forms (71.4-72.6% in amino acid sequences) and showed the highest similarity to rat CYP2C24 (88.7%), while the other hamster CYP2C forms showed high similarities among themselves (> 90.2%). CYP2C28 protein expressed in yeast catalyzed the N-demethylation of aminopyrine and benzphetamine, but did not catalyze the hydroxylation of tolbutamide, testosterone, and progesterone. Northern blot analysis demonstrated that CYP2C28 mRNA was expressed in hamster livers 1 week after birth, when the other hamster CYP2C forms were not detectable. The level of CYP2C28 mRNA increased to 3 weeks and then decreased with time in males. The level in females was lower than that in males. In adult hamsters, CYP2C28 was induced almost threefold by administration of phenobarbital but not affected by 3-methycholanthrene. On the other hand, administration of pregnenolone 16 alpha-carbonitrile induced CYP2C28 in females but not in males. These results indicate that CYP2C28 is a unique form in the hamster CYP2C subfamily.

Amino Acid Sequence↗
PubMed2002

Characterization of estrogenic compounds in medical polyvinyl chloride tubing by gas chromatography-mass spectrometry and estrogen receptor binding assay.

BACKGROUND: In 2001, the U.S. Food and Drug Administration (FDA) convened to conduct a safety assessment of a plasticizer, di(2-ethylhexyl) phthalate (DEHP), released from polyvinyl chloride (PVC) medical devices. Hospitalized patients may be exposed to high concentrations of plasticizers, antioxidants, and chemical contaminants in PVC medical devices during blood transfusion or hemodialysis, thus, making them vulnerable to more potentially adverse effects of these chemicals than healthy people. At the same time, recently, the effect of endocrine-disrupting chemicals on hospitalized patients has attracted a great deal of attention. This study aims to investigate the harmful effects of estrogenic compounds in medical PVC tubing by two approaches of gas chromatography-mass spectrometry (GC-MS) and estrogen receptor (ER) binding assay. METHODS: Residual plasticizers, antioxidants, and chemical contaminants in PVC tubing were subjected to GC-MS in the full-scan mode with an original library for plastic additives. Such residual compounds in PVC tubing were screened at very low concentrations (10(-2)-10(5) nmol/l) to determine whether they competed with fluorescein-labeled estradiol for ER (alpha). RESULTS: DEHP, 2-ethylhexanol, butylated hydroxytoluene, and 4-nonylphenol (NP) were detected in medical PVC tubing. In addition, only NP in PVC tubing was found to bind with ER. CONCLUSIONS: The current study proves that the main residual chemical for estrogenic effect was NP in medical PVC tubing.

Butylated Hydroxytoluene↗
PubMed1996

G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.

Many peptide hormone and neurotransmitter receptors belonging to the seven membrane-spanning G protein-coupled receptor family have been shown to transmit ligand-dependent mitogenic signals in vitro. However, the physiological roles of the mitogenic activity through G protein-coupled receptors in vivo remain to be elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)-B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a remarkable atrophy of the gastric mucosa macroscopically, even in the presence of severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase and histidine decarboxylase genes, respectively. Oral administration of a proton pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy of the homozygotes. These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo.

Animals↗
PubMed2006

SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity.

Receptor tyrosine kinases (RTK), such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (KIT), and fms-like tyrosine kinase 3 (FLT3), are expressed in malignant tissues and act in concert, playing diverse and major roles in angiogenesis, tumor growth, and metastasis. With the exception of a few malignancies, seemingly driven by a single genetic mutation in a signaling protein, most tumors are the product of multiple mutations in multiple aberrant signaling pathways. Consequently, simultaneous targeted inhibition of multiple signaling pathways could be more effective than inhibiting a single pathway in cancer therapies. Such a multitargeted strategy has recently been validated in a number of preclinical and clinical studies using RTK inhibitors with broad target selectivity. SU14813, a small molecule identified from the same chemical library used to isolate sunitinib, has broad-spectrum RTK inhibitory activity through binding to and inhibition of VEGFR, PDGFR, KIT, and FLT3. In cellular assays, SU14813 inhibited ligand-dependent and ligand-independent proliferation, migration, and survival of endothelial cells and/or tumor cells expressing these targets. SU14813 inhibited VEGFR-2, PDGFR-beta, and FLT3 phosphorylation in xenograft tumors in a dose- and time-dependent fashion. The plasma concentration required for in vivo target inhibition was estimated to be 100 to 200 ng/mL. Used as monotherapy, SU14813 exhibited broad and potent antitumor activity resulting in regression, growth arrest, or substantially reduced growth of various established xenografts derived from human or rat tumor cell lines. Treatment in combination with docetaxel significantly enhanced both the inhibition of primary tumor growth and the survival of the tumor-bearing mice compared with administration of either agent alone. In summary, SU14813 inhibited target RTK activity in vivo in association with reduction in angiogenesis, target RTK-mediated proliferation, and survival of tumor cells, leading to broad and potent antitumor efficacy. These data support the ongoing phase I clinical evaluation of SU14813 in advanced malignancies.

Angiogenesis Inhibitors↗
PubMed2005

Health practitioners' and health planners' information needs and seeking behavior for decision making in Uganda.

BACKGROUND: Access to reliable information is the most cost-effective and achievable strategy for sustainable improvement in health care. While several studies have described practitioners' information seeking behavior in developed countries, literature from developing countries is lacking. The aims of the study were: (i) to determine the most influential type of information for health workers' and planners' decision making; (ii) to establish the practitioners' evaluation of the availability and quality of this important information; and (iii) to establish the most commonly used/accessible sources of the information relevant for decision making in Uganda. METHODS: Self-administered questionnaires were sent to 610 health workers, planners, and administrators at the national, district and health facility levels in four districts in Uganda. Respondents were reminded three times, after which non-response was registered. Data were entered, cleaned and analysed using SPSS version 12.0. Logistic regression analysis was used to test for differences in responses. RESULTS: The response rate was 67.7% (413). The respondents indicated that personal experience (79%), discussion with colleagues (76%) and national policy and treatment guidelines (75%) were most influential when making decisions in health care and planning. They reported that most of the epidemiological information was available and of relatively good quality but there was lack of information about distribution of benefit, segregated demographic data, and social values. The most often used sources of information included; discussions with colleagues (89%), doctors' statements (85%) and text books (77%). The least frequently used sources were the internet and the library. This varied with respondents' designation and region of origin. CONCLUSIONS: Health planners and practitioners lack some of the information relevant for decision making. They tend to rely on the national policy and treatment guidelines, discussion with colleagues, and personal experience. Most frequently used sources of information are similar to previous studies. The variation in the frequency of use of the different sources of research information necessitates research to understand the barriers and careful planning of health information delivery to ensure equitable access.

Access to Information↗
PubMed2003

Analgesic efficacy of calcitonin for vertebral fracture pain.

OBJECTIVE: To evaluate the analgesic efficacy of calcitonin for treating the pain of vertebral fractures associated with osteoporosis. DATA SOURCES: Searches of MEDLINE (1966-July 2002), Cochrane Library, International Pharmaceutical Abstracts (1977-July 2002), and an extensive manual review of journals were performed using the key search terms calcitonin, analgesic, osteoporosis, vertebral fracture, and pain. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. DATA SYNTHESIS: Fractures, especially vertebral fractures, are a common complication of osteoporosis, leading to significant pain. Calcitonin has been studied for its analgesic properties. Fourteen double-blind, placebo-controlled trials that evaluated the analgesic efficacy of calcitonin for osteoporosis-related vertebral fracture pain were identified and reviewed. Thirteen of these studies demonstrated statistically significant improvement in pain or function in calcitonin-treated patients. CONCLUSIONS: Calcitonin has proven efficacy in acute pain associated with osteoporosis-related vertebral fractures. Analgesic effects are seen with intranasal, parenteral, and rectal administration. Future studies comparing calcitonin with other commonly used analgesics are needed to more clearly define its place in therapy.

Analgesics↗
PubMed2005

Effect of prophylactic amiodarone on clinical and economic outcomes after cardiothoracic surgery: a meta-analysis.

BACKGROUND: Two previous meta-analyses of amiodarone for prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery did not evaluate total hospital cost, concluded that data on stroke are incomplete, and did not evaluate the effect of clinical heterogeneity between trials. OBJECTIVE: To conduct a meta-analysis examining amiodarone's prophylactic impact on cardiothoracic surgery POAF, length of stay (LOS), stroke, and total costs. METHODS: Three reviewers conducted a systematic literature search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library (1966-SEPTEMBER 2004). Studies were included if they met the following criteria: (1) randomized controlled trial versus placebo/routine treatment, (2) coronary artery bypass graft and/or valvular surgery, (3) Jadad score > or = 3, (4) reported data on incidence of POAF or stroke, LOS, or total costs, (5) used electrocardiographic/Holter monitoring, and (6) monitored subjects for > or = 2 days. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. RESULTS: Fifteen trials were identified, including 1512 and 1429 patients in the amiodarone and control groups, respectively. Amiodarone reduced POAF (OR 0.50; 95% CI 0.42 to 0.60) and decreased stroke (n = 8 studies), LOS (n = 10), and total costs (n = 6) (OR 0.47; 95% CI 0.23 to 0.96; -0.73 days, 95% CI -0.95 to -0.51; and -dollar 1619, 95% CI -3395 to 156, respectively). Surgery type, beta-blocker use, route of administration, use of a fixed-effects model, or exclusion of unblinded/unpublished studies did not affect the overall results. No statistical heterogeneity was observed for any endpoint evaluated (p > 0.22 for all comparisons). CONCLUSIONS: Prophylactic treatment with amiodarone decreases patients' risk of POAF and stroke while reducing LOS.

Aged↗
PubMed2006

Structure-guided identification of novel VEGFR-2 kinase inhibitors via solution phase parallel synthesis.

Structural analysis of the essential binding elements of the oxindole-based kinase inhibitor (1) led to the identification of a novel class of heterocyclic-substituted pyrazolones. Knoevenagel condensation of a variety of activated methylene nucleophiles with indole or pyrrole carboxaldehydes provided a focused library of molecules, each containing elements of kinase pharmacophore probe. Initial screening for VEGFR-2 kinase inhibition eliminated several of the probes. Identification of an active pyrazolone motif and further optimization resulted in several highly potent VEGFR-2 inhibitors with cellular efficacy, anti-angiogenic activity ex vivo in rat aortic ring explant cultures, and oral anti-tumor efficacy in nude mice.

Administration, Oral↗
PubMed1987

Structural organization and regulation of the chicken estrogen receptor.

We have cloned the chicken estrogen receptor (ER) from a chicken oviduct lambda gt11 library using the human ER cDNA sequence. This chicken ER sequence is virtually identical to the recently published sequence. One noteable difference is an amino acid change from glutamine to arginine located toward the central region of the sequence. The size of the ER protein predicted from the 589 amino acids is approximately 66,000 which fits well with the range of molecular weights previously published for the calf uterine and human ER (65,000-70,000). We observed the size of the chicken ER mRNA to be approximately 7.8 kilobases which is in agreement with the previously published size of 7.5 kilobases. In vivo secondary stimulation of chicken oviduct total RNA with diethylstilbestrol does not induce chicken ER mRNA. A time course following the chicken ER mRNA levels after secondary stimulation with diethylstilbestrol indicated a decrease in mRNA levels 8 h after DES administration. A similar study was performed using progesterone for the secondary stimulation. An increase in the chicken ER mRNA levels was observed 24 h after stimulation with progesterone. Two regions of very high homology were delineated by analyzing the sequence of this chicken ER cDNA and comparing it to the sequences of the human ER, human glucocorticoid, and chicken progesterone receptors and the P75-erbA fusion product of the avian erythroblastosis virus. The first concensus region is 72 amino acids in length and the second region of high homology is 62 amino acids long. Detailed comparisons of these regions for the steroid hormone receptors and v-erb A are presented. Possible functions for the individual regions of high homology are discussed.

Animals↗
PubMed2001

[Treatment of persistent pulmonary hypertension of the newborn]

OBJECTIVE: To review the medical literature, emphasizing the new scientific advances in the treatment of persistent pulmonary hypertension of the newborn. SOURCES: Literature review using Medline and Cochrane library. SUMMARY OF THE FINDINGS: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by an increase in pulmonary vascular resistance associated with right to left shunt through the foramen ovale or ductus arteriosus, leading to marked hypoxemia and respiratory failure. The balance between the vasoconstrictor (endothelin) and vasodilator (nitric oxide and prostaglandin I2) mediators plays an important role in the regulation of the transition from fetal circulation with high pulmonary vascular resistance to postnatal circulation with low pulmonary vascular resistance. In addition to general management, cardiovascular support, the treatment of the cause of the PPHN, and the use of selective pulmonary vasodilator such as inhaled nitric oxide (iNO) are indicated. Furthermore, the combined therapy with iNO and high-frequency oscillatory ventilation significantly improved the oxygenation of patients who were refractory to iNO therapy and conventional ventilation. The practice of hyperventilation and the administration of nonspecific pulmonary vasodilators (tolazoline) should be avoided. On the other hand, the administration of surfactant to patients with PPHN due to meconium aspiration should be considered. However, if all these therapies fail, extracorporeal membrane oxygenation (ECMO) should be considered as rescue therapy. CONCLUSIONS: The mortality due to PPHN has significantly decreased with the use of new therapies, and the major concern today is the quality of life of these patients, especially in terms of neuropsychomotor development.

Journal Article↗
PubMed2001

Falls risk factors in the hospital setting: a systematic review.

The objective of this systematic review was to summarize the best available evidence on the factors that increase the risk of patients falling during hospitalization. Studies included in the review were those that involved adult patients in hospital, that attempted to identify risk factors for falling, and used a cohort or case-control research design. The search strategy covered all major databases and including MEDLINE, CINAHL, Current Contents, Psyclit, Embase and the Cochrane Library. Results were summarized by a narrative discussion, identifying risk factors that were commonly identified in a range of practice settings. Eighteen papers met the review inclusion criteria and are reported in this paper. Factors associated with an increased risk of falling include impaired mental status, special toileting needs, impaired mobility, and a history of falling. While findings are contradictory, it appears that both medications and advanced age will also influence a patient's risk of falling.

Accidental Falls↗
PubMed2006

A MEDLINE categorization algorithm.

BACKGROUND: Categorization is designed to enhance resource description by organizing content description so as to enable the reader to grasp quickly and easily what are the main topics discussed in it. The objective of this work is to propose a categorization algorithm to classify a set of scientific articles indexed with the MeSH thesaurus, and in particular those of the MEDLINE bibliographic database. In a large bibliographic database such as MEDLINE, finding materials of particular interest to a specialty group, or relevant to a particular audience, can be difficult. The categorization refines the retrieval of indexed material. In the CISMeF terminology, metaterms can be considered as super-concepts. They were primarily conceived to improve recall in the CISMeF quality-controlled health gateway. METHODS: The MEDLINE categorization algorithm (MCA) is based on semantic links existing between MeSH terms and metaterms on the one hand and between MeSH subheadings and metaterms on the other hand. These links are used to automatically infer a list of metaterms from any MeSH term/subheading indexing. Medical librarians manually select the semantic links. RESULTS: The MEDLINE categorization algorithm lists the medical specialties relevant to a MEDLINE file by decreasing order of their importance. The MEDLINE categorization algorithm is available on a Web site. It can run on any MEDLINE file in a batch mode. As an example, the top 3 medical specialties for the set of 60 articles published in BioMed Central Medical Informatics & Decision Making, which are currently indexed in MEDLINE are: information science, organization and administration and medical informatics. CONCLUSION: We have presented a MEDLINE categorization algorithm in order to classify the medical specialties addressed in any MEDLINE file in the form of a ranked list of relevant specialties. The categorization method introduced in this paper is based on the manual indexing of resources with MeSH (terms/subheadings) pairs by NLM indexers. This algorithm may be used as a new bibliometric tool.

Abstracting and Indexing↗
PubMed1996

Telemedicine: history, applications, and impact on librarianship.

This paper traces the uses of telecommunications in health care from the Civil War era to the present. Topics include the National Aeronautics and Space Administration's involvement in the origins of current telemedicine systems and the impact of television. Applications of telemedicine discussed include remote consultation and diagnosis, specialty clinical care (including examples from anesthesia, dermatology, cardiology, psychiatry, radiology, critical care, and oncology), and others (including examples of patient education, home monitoring, and continuing education). The concluding section highlights how telemedicine affects health sciences librarianship, beginning with the development of online computerized literature searching. This section also discusses the medical resources available to health sciences librarians as a result of the Internet.

Computer Communication Networks↗
PubMed2004

The development of potent non-peptidic PTP-1B inhibitors.

The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM).

Administration, Oral↗
PubMed1987

Identification, characterization, and regulation of a rat complementary deoxyribonucleic acid which encodes insulin-like growth factor-I.

A complementary DNA (cDNA) encoding rat insulin-like growth factor 1 (IGF-I) has been isolated from a kidney cDNA library. By analogy with the sequence of human and mouse preproIGF-IA this cDNA encodes rat preproIGF-I from amino acid minus 3 to amino acid 105. The predicted protein sequence shows 96% and 99% homology with the human and mouse preproIGF-I, respectively. Under stringent conditions the rat IGF-I cDNA hybridizes with at least three mRNA, messenger RNA species which have apparent sizes of 7, 1.8, and 0.7-1.1 kilobases. All three IGF-I transcripts are detectable in each of the normal rat tissues examined and the relative order of abundance in tissues from intact adult male rats is liver greater than lung greater than kidney greater than thymus greater than spleen greater than heart greater than skeletal muscle (quadriceps femoris) greater than testes greater than brain. The GH dependence of the IGF-I mRNAs was demonstrated by the administration of a single ip injection of human GH (hGH) to hypophysectomized (hypox) rats which resulted in an increase in all three transcripts in each of the tissues examined. The increase in IGF-1 mRNAs was most marked in skeletal and cardiac muscle (9.7- and 9.5-fold compared to hypox controls, respectively) and least marked in the brain. In the liver only a 4-fold increase in IGF-I expression was observed, possibly because of the relatively high level of IGF-I expression in the tissue in the hypox control rats. Each of the IGF-I messenger RNAs appeared to increase in parallel and the time course of IGF-I induction was similar in each tissue with maximal levels of IGF-I transcripts present 6 to 12 h after GH administration. A dose-dependent increase in IGF-I mRNAs was observed in most tissues of hypox rats treated for 10 days with hGH. Significant correlations between growth, as determined by body weight gain and IGF-I expression were observed in liver (r = 0.97), kidney (r = 0.90), quadriceps femoris (r = 0.95), diaphragm (r = 0.92), and thymus (r = 1.0). The IGF-I mRNA levels in tissues from rats that had been treated with the highest dose of hGH (90 microgram/rat X day) were similar to those observed in normal intact rats. This study confirms the highly conserved nature of the IGF-I precursor and provides clear evidence for the GH dependence of IGF-I gene expression in multiple tissues of the rat.

Amino Acid Sequence↗
PubMed1996

The cDNA sequence of porcine vitronectin and its expression in liver and skeletal muscle of GH-supplemented pigs.

A cDNA (1555 bp) (DNA database accession number, D61396) having a homology with human vitronectin (Vn) was isolated from a porcine liver cDNA library, and its sequence was determined. The open reading frame in the cDNA was found to code a protein with 388 amino acids, then the amino acid sequence of the protein (porcine putative Vn) was aligned to the other mammalian (mouse, rabbit, and human) Vns previously reported. The alignment revealed that the functional amino acid sequences reported as the cell attachment site, the heparin binding site, the region involved in glycosylation, and plasminogen activator inhibitor I-binding domain were conserved in the porcine putative Vn. These findings together with the fact that the calculated molecular weight and the N-terminal amino acid sequence of the putative Vn agreed with those reported by biochemical analysis on porcine Vn, led us to conclude that the cDNA isolated in the present study coded for the porcine Vn. Then, a time course study was performed to examine whether the administration of growth hormone (GH) affects Vn mRNA expression in liver and skeletal muscle, since the level of Vn mRNA was reported to be affected by inflammation, and since GH was reported to be involved in inflammation. This revealed that GH has no effect on the level of liver Vn mRNA, and that Vn mRNA level in skeletal muscle seemed to be affected following GH-injection.

Amino Acid Sequence↗