Unlike in normal rabbits, pulmonary rapidly adapting receptors (RARs) in rabbits with chronic mitral regurgitation (MR) do not respond to small changes in extravascular...Full Text Available
Polyclonal antibodies were raised in rabbits by immunization with free peptides corresponding to positions 197-222 of the human beta 1-adrenergic receptor (beta 1 peptide) and the corresponding sequence...Full Text Available
The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with (/sub 3/H)-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and true affinity constants (-log K/sub A/-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific (/sup 3/H)-1-Quinuclidinyl benzilate ...
Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and mediated by the ...
The authors used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate (["3H]QNB). At 37 degree C, specific ["3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of ["3H]QNB for its receptor. The IC_5_0 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 #mu#M, respectively. Hill coefficients were 0.67 for both, suggesting more complex interaction involving receptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that (1) ...
The plerocercoid stage of the tapeworm Spirometra mansonoides produces a functional analog of human growth hormone (hGH). Among the similarities between plerocercoid growth factor (PGF) and hGH is competition for the same receptors on rabbit liver membranes. To take advantage of this characteristic in a purification scheme for PGF, rabbit liver microsomes were solubilized in Triton X-100 and the hGH receptors were purified over an hGH affinity column. The purified receptors from six rabbit livers were coupled to Affi-Gel-10 to create a receptor affinity column which was used to purify PGF. Chromatography of crude PGF over the receptor column resulted in a 1044 fold increase in specific activity. SDS-PAGE in the presence of 2-mercaptoethanol showed that the affinity-purified PGF contained three protein bands with apparent ...
An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose dependent manner (r = 0.98). ...
Ileal dysgenesis is an uncommon condition of unknown etiology occurring in the distal ileum in the region of the vitelline duct. The CT appearance of this lesion, although not previously described to our knowledge, is characteristic. We report a patient with ileal dysgenesis who had an abdominal CT scan to evaluate chronic iron deficiency anemia and protein-losing enteropathy. Recognition of this lesion by pediatric radiologists is important; so that surgical treatment, which is simple and effective, can be initiated quickly. (orig.)
Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid ...
The authors have shown previously that the domain recognizing receptors on activated human platelets is located on the human fibrinogen {gamma} chain between residues 400 and 411. To study the correlation between the structure of this segment of the {gamma} chain and its reactivity toward receptors on ADP-activated human platelets, they designed a series of analogues containing replacements at 9 out of 12 positions. A double substitution of the normal His{sup 400}-His{sup 401} sequence by Ala-Ala reduced the inhibitory potency of the dodecapeptide 3-fold. When Lys{sup 406} was replaced by Arg, the inhibitory potency of the dodecapeptide decreased 15 times. On the other hand, substitution of Ala{sup 408} with Arg increased the inhibitory potency of the dodecapeptide 6-fold. A drastic decrease in the reactivity of the dodecapeptide toward platelet receptors was observed when Val{sup 411} was replaced by leucine or cysteine or ...
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A ...
To investigate the fate of intrinsic factor and cobalamin during cobalamin absorption, we incubated enterocytes isolated from guinea pig ileum for periods of up to 30 min with 57Co-labeled...Full Text Available
We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field...Full Text Available
To evaluate the effect of plugging the biopsy tract in rabbit liver and the pathologic changes caused by plugging materials. Thirty-two New Zealand White rabbits were divided into four groups (eight rabbits in each) and compared with one another. They were labeled group A (control), B (gelfoam), C (fibrin sealant) or D (NBCA). the liver was exposed and biopsied with an 18G disposable biopsy gun. The inner Tru-cut needle was withdrawn and plugging was undertaken through the outer cannula of the biopsy gun. Bleeding times of each material were compared. The rabbits were sacrificed and pathologically evaluated for 17 days.
The effects of homologous plasma HDL and VHDL fractions on established atherosclerotic lesions were studied in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a 0.5% cholesterol-rich...Full Text Available
The percentages of total airflows over the nasal respiratory and olfactory epithelium of female rabbits were calculated from computational fluid dynamics (CFD) simulations of steady-state inhalation....Full Text Available
The cottontail rabbit papillomavirus (CRPV)/rabbit model has been used to study oncogenicity and immunogenicity of different antigens from the papillomavirus genome and has therefore served...Full Text Available
During the anamnestic response, the sera of four rabbits immunized with a polyvalent pneumococcal vaccine contained large amounts of cryoglobulins belonging to the G and M immunoglobulin classes. These...Full Text Available
The efficacy of beta-lactam antibiotics and amikacin alone and in various combinations against Pseudomonas aeruginosa was studied in a rabbit model simulating a closed-space infection in a locally neutropenic...Full Text Available
The pharmacokinetics of two prodrugs of zidovudine (AZT), 1,4-dihydro-1-methyl-3-[(pyridylcarbonyl)oxy] ester and isoleucinyl ester (DPAZT and IAZT, respectively), were investigated in a rabbit model...Full Text Available
The investigations were conducted at the Center of Biotechnology and Molecular Diagnostics of the All-Russian Animal Husbandry Research Institute, where a number of valuable transgenic animals (rabbits, sheep, and pigs) have been produced over the course of 20 years. The article presents the blood indices of control and transgenic rabbits with an integrated insulin gene.
The authors have localized and characterized 2-125I-iodomelatonin binding sites in the chicken brain using in vitro quantitative autoradiography. Binding sites were widely distributed throughout the chicken brain, predominantly in regions associated with the visual system. The specific binding of 2-125I-iodomelatonin to discrete chicken brain areas was found to be saturable, reversible, and of high affinity. The specific binding of 2-125I-iodomelatonin (75 pm) was quantitated for 40 identifiable brain regions. Eight brain regions were chosen for binding characterization and pharmacological analysis: optic tectum, Edinger-Westphal nucleus, oculomotor nucleus, nucleus rotundus, ventral supraoptic decussation, ventrolateral geniculate nucleus, neostriatum, and ectostriatum. These regions showed no rostral-caudal gradient in 2-125I-iodomelatonin specific binding, and saturation analysis revealed a single class of high-affinity sites with KD values in the range of 33-48 pM and ...
The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. ...
The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery...Full Text Available
Structural analysis of an acetylcholine receptor from Torpedo californica leads to a three-dimensional model in which a "monomeric" receptor is shown to contain subunits arranged around a central ionophoretic...Full Text Available
Orphan G protein-coupled receptors (GPCRs) are receptors lacking endogenous ligands. Found by molecular biological analyses, they became the roots of reverse pharmacology, in which receptors are attempted...Full Text Available
Many microbial pathogens recognize oligosaccharides displayed on the surface of host cells as receptors for toxins and adhesins. These ligand-receptor interactions are critical for disease pathogenesis,...Full Text Available
AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the...Full Text Available
The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both...Full Text Available
Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat...Full Text Available
Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend...Full Text Available
To study the effect of agonist on the TRH (thyrotrophin-releasing hormone) receptor protein, an epitope-tagged receptor was stably expressed in HEK-293 cells (human embryonic kidney 293 cells) and receptor...Full Text Available
Understanding the physical characteristics of the local microenvironment in which Mycobacterium tuberculosis resides is an important goal that may allow the targeting of metabolic processes...Full Text Available
The susceptibility of 19 isolates of Haemophilus ducreyi from a recent chancroid outbreak and four reference strains was determined in vitro to 13 antimicrobial agents. The rabbit intradermal...Full Text Available
A case report of falsely elevated serum hormone values measured by radio-immunoassay (RIA) is described. The radio-immunoassays concerned have a first antibody raised in rabbits and mostly a separation technique based on a second antibody-solid phase system. The presence of heterophyle (anti-rabbit) antibodies in patients' serum is proved.
Eight rabbits and 24 guinea-pigs were exposed to a silica dust cloud of about 40,000 pp./ml. (0·3-3·0 μ) and killed at four-weekly intervals up to 30 weeks. The guinea-pigs showed...Full Text Available
The retinoic acid receptor-related orphan receptors α and γ (RORα (NR1F1) and RORγ (NR1F3)) are orphan nuclear receptors and perform critical roles in regulation of development,...Full Text Available
The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.
Seventy-one patients with intestinal injury secondary to pelvic irradiation had predominantly large bowel lesions. Seventeen cases were treated conservatively and 54 came to surgery, 28 patients having more than one operation. Following this essentially salvage surgery there were more ileal than colonic anastomotic leaks. Thirty-four patients died during the follow-up period (2-12 years), 19 from recurrent malignancy, and nine as a result of continuing radiation effects. Seventy per cent of the patients who had a radiation fistula died as a result of malignancy. Of 42000 cases of pelvic malignancy treated by irradiation over the decade 1972-1982, surgical referrals for complications constituted 1.7%, with an overall radiation-related mortality of 0.2%. It is our opinion that colostomy alone has little part to play in this condition, and a policy based on excisional surgery is suggested.
AbstractBackground: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) with...
BackgroundThe pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved...Full Text Available
The aspartate receptor involved in chemotaxis is modified by methyl esterification at four distinct glutamate residues during the adaptive response of this receptor. To explain the high degree of specificity...Full Text Available
Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissue-specific manner. This article...Full Text Available
The adenovirus fiber knob causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s), the interaction of labeled cell...Full Text Available
BackgroundThe epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available
Chemokine receptors control leukocyte chemotaxis and cell-cell communication but have also been associated with pathogen entry. GPR33, an orphan member of the chemokine-like receptor family,...Full Text Available
1. The effects of stimulation of atrial receptors on hypothalamic neurosecretory cells were investigated in anaesthetized dogs and cats. Atrial receptors were activated by stretching the left and the...Full Text Available
The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available
A specific immunoglobulin, the receptor antibody, can be found in most patients with myasthenia gravis. In order to study the kinetic properties of this antibody, serial determinations of receptor antibody,...Full Text Available
Background:Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers.Patients...Full Text Available
Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available
BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously...Full Text Available
Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen...Full Text Available
The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory neurons...Full Text Available
PurposeWe objectively quantified the gain in urethral diameter and the effect of stenting after tubularized incised plate urethroplasty in a rabbit hypospadias model. Materials and MethodsWe created a hypospadias model in 12 New Zealand white male rabbits by excising the ventral urethra. A 3 cm tattoo line was made longitudinally in the dorsal urethral plate midline. Two weeks later a 2 cm relaxing incision was made in the middle part of the tattooed line. The stretched incision width between the tattooed edges was measured, followed by urethral plate tubularization. Six rabbits were stented and 6 were nonstented. Two weeks later the animals were sacrificed and the distance separating the tattoo was measured at the midpoint of the tattooed line. Transverse sections at this point were exami...
In a series of experiments carried out on young and adult rabbits the effect of isocaloric low protein diets containing 4% or 8% protein compared with a diet containing 21% protein on Obeliscoides cuniculi infection was studied. The pathogenesis, resistance and local immunity were assessed after single infections with 10,000 larvae or reinfection with 5000 larvae. Live weight gain was reduced in young and adult rabbits fed the low protein diets, but the establishment of parasites was not substantially influenced by protein deprivation. However, development of worms in the histotrophic phase and parasite fecundity were impaired in association with the low protein diet. Moreover, mild anaemia as well as changes in the mucosal immune response as a result of infection were related to the level of dietary protein. (author). 30 refs, 6 figs, 5 tabs.
Experiments have been reported previously in which lead-212 ions with lead carrier were instilled into the lungs of anaesthetised rabbits. Experiments were also reported in which bismuth-207 chloride was instilled into rabbit lung. To check that the chloride compound was cleared in the same way as ions instilled in isolation, lead-203 chloride has been instilled in three rabbits. Measurements of absorption of ionic lead have been repeated using the radon-222 daughter, lead-214. Rates of clearance from the lung of "2"0"3Pb as the chloride and "2"1"2Pb ions are compared, and retention functions are derived. Clearance from the lung of "2"1"4Pb ions is also shown, and retention functions are derived. (U.K.).
Histamine and the histamine receptors are important regulators of a plethora of biological processes, including immediate hypersensitivity reactions and acid secretion in the stomach. In these...Full Text Available
Halothane, chloroform, and carbon tetrachloride, in the vapor and liquid phases, stimulate the water receptor of the blowfly Phormia regina. There are three successive phases of response to long-lasting...Full Text Available
A comparative and quantitative study of the tissue distribution of brain-thymus shared antigens was carried out using rabbit antisera to rat, dog and human brain homogenates, assayed on rat, dog and...Full Text Available
1. Seven unique carboxymethylcysteine-containing peptides have been isolated from tryptic digests of rabbit muscle aldolase carboxymethylated with iodo[2-14C]acetic acid in 8m-urea....Full Text Available
1. A novel phthalazine analogue taloximine (1-hydroxyimino-4(2-dimethyl-aminoethoxy)-1,2-dihydrophthalazine monohydrochloride monohydrate) stimulated respiration in conscious rabbits at doses of 7...Full Text Available
The pharmacological effects of a series of fatty acid-choline esters have been studied on the isolated rabbit heart, the isolated guinea-pig ileum and the rat stomach. The effect changed with increasing...Full Text Available
A regulatory locus on the Staphylococcus aureus chromosome, designated sar, is involved in the expression of cell wall proteins, some of which are potentially important in the pathogenesis of endocarditis....Full Text Available
Hyaluronan (HA) is important for joint cavitation, lubrication, volume regulation and synovial fluid drainage but little is known about the regulation of joint HA synthesis/secretion in vivo....Full Text Available
... Weiss, S., D. Kobiler, H. Levy, H. Marcus, A. Pass, N. Rothschild, and Z ... of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits ...
Naturally occurring, double-stranded RNA (ds-RNA)) was immunogenic when injected into mice, rats, guinea-pigs, rabbits, dogs and baboons. The response to native material administered intravenously (i.v.)...Full Text Available
An antiserum was raised in a rabbit against highly purified human liver dihydropteridine reductase (EC 1.6.99.7). Dihydropteridine reductase from human liver, in human cultured fibroblasts and in continuous...Full Text Available
Antibodies of the IgM type present in rabbit anti-epiglycanin antiserum were purified by (NH4)2SO4 precipitation and by ion-exchange, affinity and gel-filtration chromatography. After papain treatment...Full Text Available
ABSTRACTObjectivesTo test the feasibility of human immune globulin (IG, Gamimune N, 10%) as a new treatment for endophthalmitis, the ocular tolerance, distribution,...Full Text Available
Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits....Full Text Available
... The costal plain still supports Jarrah (Eucalyptus marginata ) forest, dense woodlands, coastal heath and diverse swamplands. Many species of plants are endemic. 20 species of mammals and 12 species of introduced mammals including with feral pigs, rabbits and foxes of particular concern....
1. Gamma globulin metabolism and distribution were studied employing rabbit gamma globulin (RGG)I(131) 24 times in 13 control rabbits. Similar studies were performed before and during the ananmestic response in 4 rabbits previously sensitized with a polyvalent pneumococcal vaccine. 2. During the ananmestic response, gamma-globulin levels increased from 1.0 to 6.0 gm/100 ml, and the gamma-globulin pool increased from 0.7 to 4.7 gm/kg. There was no change in the intravascular-extravascular partition of gamma globulin. 3. Gamma globulin degradation increased from 0.06 to 0.33 gm/kg/day during the 28 days of the immunization period while gamma globulin synthesis increased even further to average 0.47 gm/kg/day. Following the attainment of elevated gamma globulin levels the fractional rate of RGG-I(131) turnover increased from 8.0 to 12.5 per cent/day. 4. No differences were noted in the metabolism of homologous or autologous ...
Assessment of subtle changes in the primary macromolecular components of cartilage, proteoglycan (PG) and collagen, is critical for the diagnosis of early stages of osteoarthritis (OA), but...Full Text Available
Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular...Full Text Available
ObjectivesWe examined the expression of Rho Kinase (ROK) isoforms in young and old rabbit’s detrusor smooth muscles (SM) during the progression of short term...Full Text Available
In vivo, mammalian lenses have the capacity to effect fully reversible changes in shape, and possibly volume, during the accommodation process. Isolated lenses also change shape...Full Text Available
Reaggregated cells from 6- to 8-day-old mouse cerebella have been used to raise antibodies in rabbits. The interaction of these antibodies with cerebellar cell surface components was assessed by cytotoxicity...Full Text Available
Tooth enamel biomineralization is mediated by enamel proteins synthesized by ameloblast cells. Two classes of proteins have been described: enamelins and amelogenins. In lower vertebrates the absence...Full Text Available
The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.
Objective: To evaluate technical feasibility and acute and subacute radiotolerance of a self-expandable stent loaded with {sup 125}I seeds in the rabbit esophagus. Methods: A self-expandable stent designed for esophageal application was made of 0.16 mm nitinol wire and loaded with {sup 125}I seeds (CIAE-6711). Twenty-seven stents with three different radioactive dosages (n = 9 in each dosage group) were implanted in the esophagus of healthy rabbits, while nine stents alone were used as controls. The stents were perorally deployed into the esophagus under fluoroscopic guidance. Radiological follow-up included plain chest film, CT scan, and barium esophagography which were undertaken in all rabbits of each group at 2, 4, and 8 weeks, respectively, which were correlated to histopathological findings. The stented esophageal segments along with their adjacent tissues were harvested for histopathological examinations. Results: ...
BackgroundThe effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate (AMP) challenge...Full Text Available
BackgroundThe orphan nuclear receptor estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily. It was identified through a search for genes...Full Text Available
Although the radioreceptor method is widely used for estrogen receptor assay in human tissue, it has several limitations and a number of alternative methods are being explored. An immunohistochemical method of estrogen receptor assay using a specific antibody to estradiol has been proposed as a suitable alternative. The present study was designed to evaluate the validity of this method in detecting true estrogen receptors in human tumor tissue. Using radioiodinated antibody to estrogen, we have demonstrated that the estrogen antibody can detect the estrogen when it is bound to 4S type receptor but is unable to bind to estrogen when the hormone is bound to 8S type receptor. Our observations suggest that the immunohistochemical method of detection of intracellular cytosolic receptor for estrogen is not a suitable alternative to the currently used radioreceptor ...
An /alpha//sub 2/-adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet /alpha//sub 2/-adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet /alpha//sub 2/-adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the /alpha//sub 2/-adrenergic ligand (/sup 3/H)rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the /alpha//sub 2/B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet /alpha//sub 2/-adrenergic receptor (/alpha//sub 2/A) lies on chromosome 10. This ...
Insulin receptors on the surface of isolated rat adipocytes were photoaffinity labeled at 12 degrees C with the iodinated photoreactive insulin analogue, 125I-B2 (2-nitro-4-azidophenylacetyl)-des-PheB1-insulin, and the pathways in the intracellular processing of the labeled receptors were studied at 37 degrees C. During 37 degrees C incubations, the labeled 440-kDa insulin receptors were continuously internalized (as assessed by trypsin inaccessibility) and degraded such that up to 50% of the initially labeled receptors were lost by 120 min. Metabolic poisons (0.125-0.75 mM 2,4-dinitrophenol (DNP) and 1-10 mM NaF), which led to dose-dependent depletion of adipocyte ATP pools, inhibited receptor loss, and caused up to 3-fold increase in intracellular receptor accumulation. This effect was due to inhibition of intracellular receptor ...
Absorption of lead is known to be enhanced during infancy. In this study, the sites of intestinal accumulation of Pb by suckling rats have been determined under various conditions using "2"0"3Pb as a tracer. When "2"0"3Pb was administered intragastrically (IG) as a soluble salt, accumulation occurred primarily in the duodenum, regardless of dose and vehicle. In contrast, when rat pups suckled from a dam which had received "2"0"3Pb, the only region of the small intestine showing accumulation of radioactivity was the ileum. To confirm that these differences were not related to the route of administration, rat milk was labeled with "2"0"3Pb and was then used for IG administration. Once again, accumulation (4 hr post-administration) was confined to the ileum. When the dose was increased 10-fold, milk Pb displayed some accumulation in duodenal tissue, but very much less than that of soluble Pb at the same time and dosage. At 20 hr postadministration, there was negligible "2"0"3Pb in any ...
To assess the technical feasibility of a newly designed stent-like electrode in rabbits. A stent-like electrode was knitted from a single thread of nitinol wire and interconnected to a generator using similar wire. In order to gauge the extent of radiofrequency ablation (RFA), we measured the depth of the ablated area in cow liver using a combination of 180-sec time intervals and 20- watt power increments. For data processing, Cox regression analysis was used. RFA was also applied to the small intestine of rabbits using this stent-like electrode under six different sets of conditions: 10 watts for 1 min, 10 watts for 2 mins, 20 watts for 1 min, 20 watts for 2 mins, 30 watts for 1 min, and 30 watts for 2 mins. To determine the gross and microscopic findings, six animals were sacrificed immediately after the procedure and the results obtained under the different sets of conditions were correlated. Eight rabbits were monitored ...
Summary Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB r...
A clone encoding a human D{sub 2} dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D{sub 2} receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.
Calcitonin gene-related peptide (CGRP) was localized by an immunocytochemical technique in the thyroid-parathyroid complexes of rat, guinea pig, rabbit, and in normal human thyroids and parathyroids. Human medullary carcinomas and parathyroid adenomas were also studied. In man and all animal species examined CGRP was present in the parafollicular cell, however, in guinea pigs only in small amounts. Except in rabbits, presence of CGRP was demonstrated in nerves of the thyroid and parathyroid capsule as well as in the nerve fibers of the capsular blood vessels. In the thyroid of guinea pigs CGRP was also noted in nerve fibers and in blood vessel walls between follicles. CGRP was also present in the parathyroid glands of rat and man, in nerve fibers localized between parathyroid cells. In rabbit the parafollicular cells between parathyroid cells also expressed CGRP immunoreactivity. No CGRP was noted in the parathyroids of the ...
Glycosaminoglycans synthesized by cultured rabbit smooth muscle cells were isolated after incorporation of (/sup 3/H)-glucosamine into glycosaminoglycans in the presence or absence of 10% fetal bovine serum. Glycosaminoglycans were quantitated by two-dimensional electrophoresis after proteolytic digestion of the cell layers and media. The results show that the presence of serum has no effect on the chondroitin sulfate, heparan sulfate and dermatan sulfate content of the cell layers. The incorporation of (/sup 3/H)-glucosamine into hyaluronic acid of the cell layers was three times higher in the presence of serum. In the medium , the quantity of hyaluronic was two times higher in the presence of serum while the other glycosaminoglycans remained unchanged. The incorporation of (/sup 3/H)-glucosamine into hyaluronic acid was unaffected by the presence of serum. Specific proteoglycans were isolated from medium after with (/sup 35/S)-sulfate and (/sup 3/H)-serine by ...
A multifunctional protein kinase, purified from rat liver as ATP-citrate lyase kinase, has been identified as a glycogen synthase kinase. This kinase catalyzed incorporation of up to 1.5 mol of and)2numberSPO4/mol of synthase subunit associated with a decrease in the glycogen synthase activity ratio from 0.85 to a value of 0.15. Approximately 65-70% of the TUPO4 was incorporated into site 3 and 30-35% into site 2 as determined by reverse phase high performance liquid chromatography. This multifunctional kinase was distinguished from glycogen synthase kinase-3 on the basis of nucleotide and protein substrate specificities. Since the phosphate contents in glycogen synthase of sites 3 and 2 are altered in diabetes and by insulin administration, the possible involvement of the multifunctional kinase was explored. Glycogen synthase purified from diabetic rabbits was phosphorylated in vitro by this multifunctional kinase at only 10% of the rate compared to synthase ...
Purpose: The lifelong persistence of foreign bodies within the arteries may contribute to restenosis. Thus,biodegradable devices might decrease recurrence rates. Methods: Eleven polyhydroxybutyrate biodegradable stents and 13 tantalum stents were implanted into the iliac arteries of New Zealand white rabbits for up to 30 weeks. After killing the animals,the specimens were harvested, fixed in formalin, processed in paraffin,and stained. Results: Polyhydroxybutyrate instigated intense inflammatory and proliferative reactions with an increase in collagen (2.4- to 8-fold vs native segments), thrombosis and in-stentlumen narrowing (375.5-606.6 mm vs 655.6 #+-# 268.8 mm in native segments). The elastic membranes were destroyed in all specimens. The tantalum stents increased the in-stent lumen progressively (769.7 #+-# 366.6 mm vs 1309.9 #+-# 695.3 mm),penetrated the external elastic membrane, and increased mural collagen content (6- to 8.6-fold vs native segments). ...
Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available
The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABAA and Drosophila melanogaster...Full Text Available
The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI 32.7 ± 3.7)...Full Text Available
The plant hormone cytokinin is perceived by membrane-located sensor histidine kinases. Arabidopsis (Arabidopsis thaliana) possesses three cytokinin receptors: ARABIDOPSIS HISTIDINE...Full Text Available
BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available
Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available
SUMMARYThe cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on target cells. Structural studies of...Full Text Available
Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation...Full Text Available
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...Full Text Available
The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2...Full Text Available
G-protein-coupled receptor signalling has been suggested to be voltage dependent in a number of cell types; however, the limits of sensitivity of this potentially important phenomenon are unknown. Using...Full Text Available
Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia...Full Text Available
We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice....Full Text Available
1. The structural requirements of an allosteric barbiturate binding site on acetylcholine receptor-rich membranes isolated from Torpedo electroplaques have been characterized by the ability of fourteen...Full Text Available
Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on...Full Text Available
The neonatal Fc receptor FcRn provides IgG molecules with their characteristically long half-lives in vivo by protecting them from intracellular catabolism and then returning them to...Full Text Available
There is increasing evidence that receptor-mediated events impact one or more stages responsible for tumor development in experimental animals and humans. Although many chemicals and endogenous hormones...Full Text Available
The presence of albumin structures with the capacity to bind to a surface receptor in group C and G streptococci was studied in serum samples from 45 mammalian species representing 15 different orders,...Full Text Available
Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available
Binding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand-activated EGFR is also rapidly internalized...Full Text Available
BackgroundBaculovirus, which has a width of 40 nm and a length of 250-300 nm, can display functional peptides, receptors and antigens on its surface by their fusion with a baculovirus...Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available
Antagonists for kainate receptors (KARs), a family of glutamate-gated ion channels, are efficacious in a number of animal models of neuropathologies, including epilepsy, migraine pain, and anxiety....Full Text Available
Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system and participate in the synaptic process particularly associated with acetylcholine, GABA, and glutamate...Full Text Available
Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present...Full Text Available
The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available
BackgroundApolipoprotein E (ApoE), a cholesterol carrier associated with atherosclerosis, is a major risk factor for Alzheimer's disease (AD). The low-density lipoprotein receptor...Full Text Available
We have characterized the kinetic response of gene targets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available
Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor...Full Text Available
The receptors for IGF-I (IGF-IR) and insulin (IR) have been implicated in physiological cardiac growth, but it is unknown whether IGF-IR or IR signaling are critically required. We generated mice with...Full Text Available
TCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic...Full Text Available
Osteoblasts are the primary cells responsible for bone formation. They also support osteoclast formation from bone marrow precursors in response to osteotropic factors by inducing receptor activator...Full Text Available
The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous...Full Text Available
To study the expression of Fc receptors in human alveolar macrophages (AM), the cells were collected from 12 healthy controls and 22 patients with sarcoidosis and the activity involved in binding to...Full Text Available
TSH receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs in Graves’ disease (GD-IgG). Whether TSHR is involved in the pathogenesis of thyroid associated...Full Text Available
Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR...Full Text Available
OBJECTIVEPrevious studies showed that genetic deletion or pharmacological blockade of the receptor for advanced glycation end products (RAGE) prevents the early structural changes...Full Text Available
The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available
Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable...Full Text Available
The extracellular domain of human fibroblast growth factor receptor (XC-FGF-R) was expressed in Escherichia coli. The protein was purified to homogeneity and the interaction with basic fibroblast growth...Full Text Available
Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and ...Full Text Available
Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha...Full Text Available
The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased κ-opioid receptor (KOR)...Full Text Available
The acetylcholine receptor from the electric tissue of Torpedo californica is a large, integral membrane protein containing four different types of polypeptide chains. The structure of the purified...Full Text Available
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
Single-channel currents from acetylcholine receptor channels of garter snake neuromuscular junctions were recorded using the patch-clamp technique. Low concentrations of acetylcholine or carbamylcholine...Full Text Available
IntroductionVarious multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing...Full Text Available
BACKGROUNDOff-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1...Full Text Available
Gamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain...Full Text Available
Abstract Purpose: We investigated the effects of various rinsing and healing protocols on corneal wound repair and inflammation following alkali burn in rabbits. Methods: We conducted in vitro, in vivo and ex vivo studies. First, different rinse solutions were tested in vitro after incubation of ocular cells with methanol or NaOH. Cell viability was then assessed using the neutral red test (cytofluorometry). Second, NaOH was applied to rabbit corneas and associations of rinse solutions (NaCl 0.9% or controlled ionization marine solutions) with N-acetylcysteine or vegetable oils (from Calophyllum inophyllum and Aleurites moluccana) were tested in vivo. The regeneration of the corneal epithelium and the infiltration of inflammatory cells were evaluated using in vivo confocal microscopy and e...
The purpose of this study was to investigate whether hydroxyapatite (HAp) coating could induce polyethylene terephthalate (PET) artificial ligament graft osseointegration in the bone tunnel. Twenty-four New Zealand white rabbits underwent artificial ligament graft transplantation in bilateral proximal tibia tunnels. One limb was implanted with HAp-coated PET graft, and the contralateral limb was implanted with non-HAp-coated PET graft as control. The rabbits were randomly sacrificed at four and eight?weeks after surgery. The loads to failure of the experimental group at eight?weeks were significantly higher than those of the control group (p?=?0.0057). Histologically, application of HAp coating induced new bone formation between graft and bone at eight?weeks compared with the controls. Rea...
Purpose: To evaluate the therapeutic effect of heated (60 deg. C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3 cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 deg. C) (1 mL), lipiodol (60 deg. C) (1 mL) or control (physiological saline (37 deg. C) (1 mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected ...
Aim: This study was performed: 1) to assess the relationship between blood flow velocity in the internal carotid artery (CBFICA) and pial artery pulsation (cc-TQ) and 2) to evaluate flow-induced changes in pial artery compliance. Methods: Experiments were performed on 10 crossbred male rabbits. Heart rate (HR), blood pressure (BP), left ventricle ejection fraction (LVEF), CBFICA, the systolic-diastolic blood volume fraction in the brain circulation (CBFSDF) and cc-TQ were recorded after glucagon and acetazolamide administration. cc-TQ was measured with near-infrared transillumination back scattering sounding (NIR-T/BSS), LVEF and CBFSDF with gated scintigraphy and BP and CBFICA with electromagnetic pressure and flow transducers, respectively. Doses of drugs were chosen to exert a haemodyna...
BackgroundTo evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X3 and P2X2/3 receptor agonist α,β-methyleneATP...Full Text Available
P2X1 receptors for ATP contribute to signalling in a variety of cell types and following stimulation undergo rapid desensitisation (within 1 s), and require ∼5 min to recover. In HEK293 cells...Full Text Available
SummaryThe transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification....Full Text Available
The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered....Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factor receptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available
The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly....Full Text Available
Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized....Full Text Available
We have cloned and characterized a 77-kDa oestrogen receptor (ER) from an oestrogen-independent subclone of the MCF-7 human breast cancer cell line. This receptor contains an in-frame, tandem duplication...Full Text Available
The study of chemoattractant receptors on human monocytes had been limited by the lack of a radioligand suitable for use with the small numbers of cells routinely available from human donors. A new synthetic oligopeptide radioligand f(/sup 35/S)Met-leu-phe, with a higher specific radioactivity than was available with the tritiated compound, was used to characterize a chemoattractant receptor on freshly isolated human blood monocytes. These cells bind f(/sup 35/)met-leu-phe with a dissociation constant (KD) of 30.2 +/- 5.6 nM and contain 84,000 +/- 11,300 receptors per cell. f(/sup 35/)met-leu-phe does not bind specifically to blood lymphocytes. The specificity of the oligopeptide receptor on monocytes is indistinguishable from the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes. Using f(/sup 35/)met-leu-phe, it will now be feasible to study the ...
Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein...Full Text Available
... The dawn of Bio-Mecha and a Biomechanical Revolution May 31 2011: Hi Julian, Yes, but i dont think we would ... The dawn of Bio-Mecha and a Biomechanical Revolution May 31 2011: A BBC Documentary: All Watched Over by Machines of Loving ... The dawn of Bio-Mecha and a Biomechanical Revolution May 17 2011: Ed Boyden: A light switch for neurons is an amazing ... The dawn of Bio-Mecha and a Biomechanical Revolution May 16 2011: Thank you Meher Like Spring Rabbit, its a great contribution....
The use of tick vaccines in mammalian hosts has been shown to be the most promising alternative tick control method to current use of acaricides, which suffers from a number of limitations. However,...Full Text Available
BackgroundHerpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction...Full Text Available
Correlates between immunological parameters and protection against Bacillus anthracis infection in animals vaccinated with protective antigen (PA)-based vaccines could provide surrogate markers to evaluate the putative protective efficiency of immunization in humans. In previous studies we demonstrated that neutralizing antibody levels serve as correlates for protection in guinea pigs (S. Reuveny et al., Infect. Immun. 69:2888-2893, 2001; H. Marcus et al., Infect. Immun. 72:3471-3477, 2004). In this study we evaluated similar correlates for protection by active and passive immunization of New Zealand White rabbits. Full immunization and partial immunization were achieved by single and multiple injections of standard and diluted doses of a PA-based vaccine. Passive immunization was carried out by injection of immune sera from rabbits vaccinated with PA-based vaccine prior to challenge with B. anthracis spores. Immunized ...
1. Amino acid sequences covering the region between residues 173 and 248 [adopting the numbering system proposed by Lai, Nakai & Chang (1974) Science 183, 1204-1206] were derived for trout (Salmo...Full Text Available
Incorporation of /sup 32/P from (gamma-32P)ATP into tyrosine residues of the insulin-like growth factor (IGF)-II receptor was observed in a Triton X-100-insoluble fraction of rat adipocyte plasma membranes. IGF-II receptor phosphorylation proceeded to a stoichiometry of approximately 0.5 mol of phosphate/IGF-II binding site after 10 min of incubation at 4 degrees C. A Km for ATP of 6 microM was calculated for this phosphorylation reaction. Addition of IGF-II caused an approximately 2-fold increase in tyrosine phosphorylation of the IGF-II receptor in this preparation. In contrast, phosphorylation of angiotensin II by the Triton X-100 washed membranes was not stimulated by IGF-II. Incubation of purified receptor immobilized on IGF-II agarose or of receptor-enriched low density microsomal membranes with (gamma-32P)ATP did not result in appreciable incorporation of (/sup 32/P)phosphate ...
The authors have investigated insulin receptor phosphorylation in differentiated cultured BC3H-1 myocytes. As for other insulin-responsive cell systems in partially purified wheat germ agglutinin receptor preparations, insulin stimulates the phosphorylation of its own receptor (95K ..beta..-subunits) in a dose dependent manner (0-400 nM), as identified by immunoprecipitation with antiinsulin receptor antibodies and SDS-PAGE. In the same preparations they show that 12-0-tetradecanyl phorbol acetate (TPA), which in many respect ..beta..-subunits in the same dose dependent manner (0-5 ..mu..M). In addition, antiinsulin receptor antibodies (B-10) also induced phosphorylation of mimics insulin action, also induced phosphorylation of the insulin receptor and HPLC tryptic maps of the /sup 32/P-labeled ..beta..-subunit were identical to those for insulin-induced ...
The authors have been involved for the last few years in developing high affinity sigma-receptor-specific radiopharmaceuticals for use in nuclear medicine. They recently demonstrated that sigma-1 receptors are expressed in human melanoma cells and that sigma receptors could be used as external markers for non-invasive imaging. In order to determine the presence of sigma receptors in other human tumors they have screened numerous non-small cell lung carcinoma, melanoma and breast cancer cell lines. All of these cell lines expressed high sigma receptor densities using commercially available ["3H]-(+)-pentazocine or ["3H]DTG tritiated sigma ligands. Therefore, a sigma ligand with high affinity in both sigma-1 and sigma-2 subtype pharmacological assays could be potentially useful for imaging a variety of primary and metastatic sites of various origins. The authors describe recent ...
Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in receptor concentration. Scatchard analysis of ...
Methylxanthines and their derivatives are antagonists at cell surface adenosine receptors. They report here a systematic study of xanthine structure-activity relationships which compares potency at two adenosine receptor subtypes, R/sub a/ and R/sub i/. Adenylate cyclase stimulation (R/sub a/ in platelet membranes) and inhibition (R/sub i/ in adipocyte membranes) were used as models of receptor activation. K/sub i/ values were obtained by Schild analysis. The orders of potency of the xanthines to attenuate the effects of adenosine analogues were similar to those previously reported. Earlier work utilizing radioligand binding (R/sub i/ and (/sup 3/H) cAMP formation (R/sub a/) claimed that IIX and PACPX are at least 10 and 400 fold, respectively, more potent at R/sub i/ than at R/sub a/. However, in their assays which utilize modulation of receptor-coupled adenylate cyclase, the xanthines show little ...
The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate...Full Text Available
SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available
SUMMARYTestosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior...Full Text Available
The rejection thresholds of Phormia regina Meigen for twenty-four glycols have been determined. A definite relationship between the concentration of the test material and the distribution...Full Text Available
There is considerable evidence that purines are vasoactive molecules involved in the regulation of blood flow. Adenosine is a well known vasodilator that also acts as a modulator of the response to...Full Text Available
Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological...Full Text Available
Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the ...
A study was made of the kinetics of L-(/sup 3/H)quinuclidinyl benzilate binding with membrane-bound muscarine cholinoreceptors from the rat brain. Determination was made of the rate constants of this process, and constants as a function of ligand concentration was investigated, indicating that there is a complex mechanism of interaction of antagonists with muscarine receptor. With up to 3.5 nM concentrations of L-(/sup 3/H)quinuclidinyl benzilate, the binding reaction occurs in two stages: rapid equilibrated binding is followed by a slow process of conformational isomerization of the receptor-ligand complex. At higher ligand concentrations, there is additional drastic increase in constant of rate of ligand binding a new plateau is reached. Such dependence of rate constant on ligand concentration is indicative of the cooperative nature of interaction between antagonists and muscarine receptors. This is possible if there are ...
The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles...Full Text Available
BackgroundWhereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development,...Full Text Available
This paper describes attempts to isolate and characterize glycosaminoglycan (GAG)-binding molecules on the surface of lymphocytes and lymphoma cell lines and relate their expression to splenic and lymph...Full Text Available
OBJECTIVES:To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies...Full Text Available
Carbohydrate-directed endocytosis is mediated by a receptor, the hepatic binding protein; it is responsible for the clearance of galactose-terminated glycoproteins from the circulation. This process...Full Text Available
Measurements of the taste thresholds of blowflies for a wide variety of carbohydrates, presented individually and in combination, showed that the stimulating effects of the compounds are not always...Full Text Available
To assess the influence of a live attenuated oral vaccine against porcine post-weaning colibacillosis (PWC) induced by enterotoxigenic Escherichia coli (ETEC) on mucosal lymphoid cell CD45 isoforms expression, experimental group of weaned pigs (n=6) was immunized orally with F4ac+ non-ETEC strain (day 0) and challenged with F4ac+ ETEC strain 7 days latter. Non-immunized ETEC-infected pigs (n=6) served as control. All pigs were killed on post-challenge day 7. The small intestine was excised for isolation of jejunal lamina propria (JLP) and ileal Peyer's patch (IPP) lymphocytes and immunohistochemical studies. The results obtained by immunophenotyping of isolated cells show that the proportion of CD45RA+ and CD45RC+ JLP, but not IPP, cells were higher in the non-ETEC-immunized ETEC-infected pigs versus non-immunized infected. Additionally, while CD45RA+ JLP cells increased only slightly, the expression of CD45RC isoform on the JLP cells was significantly higher ...
Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-?, IL-1? and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these ...
Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable (free) hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of ({sup 3}H)hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of {sup 3}H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is ...
Rat lung and liver microsomes did not undergo lipid peroxidation in the absence of iron when incubated with NADPH and concentrations of paraquat ranging from 10/sup -7/ to 10/sup -2/ M. Paraquat also did not stimulate rat liver and lung microsomal peroxidation induced by added iron and NADPH, and was inhibitory at concentrations above 10 ..mu..M. Similarly, no stimulation of peroxidation was produced by paraquat in rabbit or human lung microsomes; however, under similar conditions, paraquat enhanced NADPH/iron-dependent peroxidation in mouse lung and liver microsomes obtained from rats sacrificed at 12, 18, and 24 hr following a lethal dose of paraquat (50 mg/kg, ip), there was no loss of vitamin E or increase in susceptibility to in vitro peroxidation which would be expected if lipid peroxidation had occurred in vivo although extensive lung damage developed during this time period. These results indicate that paraquat does not cause pulmonary toxicity by ...
A new /sup 99m/Tc-phosphine-isocyanide complex with the general structure (/sup 99m/Tc (DEPE)/sub 2/(CNR)/sub 2/)/sup +/ has been synthesised and tested in animals and one human. In three animal species (rat, rabbit, dog), the complex is an efficient myocardial imaging agent, while in humans it remains in the blood pool. The complex is 100% protein bound in animals and humans, but whereas in humans it is attached to a 51.5 kdalton protein (probably prealbumin), in rabbits it appears to be bound to a larger macromolecule (M.W.>100 kdalton). The efficiency of the complex for blood pool labelling was tested in a human volunteer and compared with the standard in vivo red cell labelling technique with stannous pyrophosphate. A satisfactory radionuclide angiogram could be performed with less than 370 MBq of the complex. The count rate for the complex (cps/MBq) was 15% higher than that obtained with the labelled red cells and the absence of splenic ...
The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.
Central penetrating excisional wounds were made in the corneas of 12 rabbits and 10 trout. The scar tissue and the surrounding cornea were compared using a new method for assessing inorganic elements in the cornea: the scanning electron microscopy and energy dispersive analysis of x-ray (EDAX). Semiquantitative determination of inorganic elements within the range of atomic numbers 9-93 in the periodic system was performed, comparing the relative concentration of those elements in the scar tissue to the surrounding cornea. Results showed that calcium was the only element higher in the healing wound than in the surrounding cornea.
We irradiated proton beams on the ears of rabbits and the Harding-Passey mouse melanoma and observed their morphological change. We used 52 MeV proton beams from the INS-FM cyclotron. We adjusted the energy of the proton beams to be at the plateau part of the Bragg curve, at the half-way point of the Bragg peak, and at the Bragg peak. The amount of radiation was 5000rad in each case. The Harding-Passey mouse melanoma was transplanted into the subcutan of a three week old mouse. In this experiment, we used tumors, the diameter of which grew up to 1.5-2cm in 2-3 weeks after the transplantation. Using the jroscope, we observed both lightly and severely damaged cells. Using proton irradiation with the Bragg peak located at depth of 1mm in the rabbit's ears, we studied the change in the tissue. Irradiated epidermis fell off and was eroded because of radiation damage, but the rear surface of the rabbit's ears ...
A comparison of the concentration-response effects of inhaled ozone (O/sub 3/) and phosgene (COCl/sub 2/) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation toxicity studies. The effect of 4-h exposures to ozone at concentrations of 0.2, 0.5, 1.0, and 2.0 ppm, and to COCl/sub 2/ and 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters, and mice. Lavage fluid protein (LFP) accumulation 18-20 h after exposure was used as the indicator of O3- and COCl/sub 2/-induced pulmonary edema. All species had similar basal levels of LFP (250-350 mg/ml) when a volume of saline that approximated the total lung capacity was used to lavage the collapsed lungs. Ozone effects were most marked in guinea pigs, which showed significant effects at 0.2 ppm and above. Mice, hamsters, and rats showed effects at 1.0 ppm O3 and above, while rabbits responded ...
SummaryThe receptors for the second messenger InsP3 comprise a family of closely related ion channels that release Ca2+ from intracellular stores, most prominently...Full Text Available
BackgroundCannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB1 and CB2receptors mediate this therapeutic effect...Full Text Available
To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer ...
BackgroundThe status of estrogen receptor-α (ERα) is critical to the clinical prognosis and therapeutic approach in breast cancer. ERα-negative breast cancer...Full Text Available
Background2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca2+ influx and...Full Text Available
1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+...Full Text Available
The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available
1. The effects on micturition of RP 67,580, a selective NK1 receptor antagonist, and SR 48,968, a highly, potent antagonist at NK2 receptor sites, given intrathecally (i.t.) or intra-arterially (i.a.)...Full Text Available
σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available
We have previously described an allelic polymorphism in the V beta 6.1 T-cell receptor gene. The V beta 6.1B allele is associated with disease in a subgroup of patients with juvenile rheumatoid arthritis....Full Text Available
Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp...Full Text Available
Airway ciliated cells express an ATP-gated P2X receptor channel of unknown subunit composition (P2Xcilia) which is modulated by Na+ and by long exposures to ATP. P2Xcilia...Full Text Available
AimsTo characterize the pharmacokinetics of terbogrel, a new combined thromboxane A2 (TxA2) receptor and synthase inhibitor, in healthy human subjects after...Full Text Available
The effects of neuroactive steroids on the function of GABAAreceptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with α1...Full Text Available
Although peroxisome proliferator-activated receptor alpha (PPARα) is closely associated with myocardial fatty acid metabolism, the pathophysiological role of PPARα in myocardial infarction...Full Text Available
Peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular 125I-ASOR is undegraded, dissociated ...
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular 125I-ASOR is undegraded, dissociated ...
(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied ...
The immunolocalization of the low density lipoprotein receptor-related protein 1 (LRP1) and its ligand alpha 2-Macroglobulin (α2M) was examined in tissues from human donor...Full Text Available
Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor β superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin...Full Text Available
Backgroundβ2-Adrenergic receptors (β2AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available
An unusual S1-nuclease sensitive microsatellite (STMS) has been found in the single copy, rat polymeric immunoglobulin receptor gene (PIGR) terminal exon. In Fisher rats, elements within or beyond the...Full Text Available
Using an anti-receptor mAb that blocks the attachment of echovirus 7 and related viruses (echoviruses 13, 21, 29 and 33), we have isolated a complementary DNA clone that encodes the human decay-accelerating...Full Text Available
The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and...Full Text Available
Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5+ B-cell population, termed...Full Text Available
The substantia nigra pars reticulata (SNR) controls seizures in a sex-specific manner. At postnatal day 15 (P15), SNR infusion of GABAAreceptor agonist muscimol have proconvulsant...Full Text Available
T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X7receptors play a key...Full Text Available
This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary...Full Text Available
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available
Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R)....Full Text Available
This report investigates acute changes in the sensitivity of 5-HT1Areceptors in dorsal raphe (dr) neurons in response to elevated serotonin. DR neurons were isolated from adult rats...Full Text Available
α1-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available
1-Naphthylphthalamic acid (NPA) is a specific inhibitor of polar auxin transport that blocks carrier-mediated auxin efflux from plant cells. To allow identification of the NPA receptor thought to be...Full Text Available
The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available
The temporal development of the effect of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) on the ultrastructure composition and GABA receptor expression in cerebellar granule cells was investigated by quantitative electron microscopy (morphometric analysis) and GABA binding assays. It was found that the cytoplasmic density of smooth endoplasmic reticulum was decreased, while the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus, vesicles and coated vesicles was greatly enhanced after exposure of the cells to THIP (150 microM) for only 1 hr. In cerebellar granule cells exposed to THIP (150 microM) for 3 hr low affinity GABA receptors were induced. These findings show that the effect of THIP on the ultrastructure composition and GABA receptor expression in cultured cerebellar granule cells may be interrelated and moreover it is likely that the turn-over of GABA receptors is ...
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated ...
By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the ...
The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, the authors report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. They have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. They localized (i) RXR[alpha] (RXRA) to chromosome 9 band q34.3; (ii) RXR[beta] (RXRB) to chromosome 6 band 21.3; and (iii) RXR[gamma] (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three RXRs. Interestingly, ...
(3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without ...
[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without ...
Full text: The maturation of chicken forebrain is protracted and occurs well after synapse formation providing a good model for studying mechanisms of brain maturation. Using microslices from immature (10 day) and adult chicken forebrain prepared after decapitation, we have examined functional properties of NMDA and AMPA receptors by measuring agonist-induced uptake of "4"5Ca"2"+ . The rate and extent of NMDA induced "4"5Ca"2"+ accumulation decreased during maturation with no change in EC_5_0. The rate and extent of the AMPA induced response also decreased with a 60-fold increase in EC_5_0. However, the total NMDA receptor content did not change as indicated by 3 H-MK801 binding and NR1 immunoreactivity in P2 fractions. Similarly, there was no change in the B_m_a_x of "3H-AMPA, though there was a two-fold increase in K_D, and little or no change in the immunoreactivity in GluR1, 2, 2/3 or 4. These results suggest that it is the regulation of ...
Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide ...
Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. ["1"1C]CUMI-101, proposed as the first 5-HT_1_A receptor agonist PET ligand, has been reported to behave as a potent 5-HT_1_A agonist in a cellular system stably expressing human recombinant 5-HT_1_A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: ["3"5S]-GTP#gamma#S binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT_1_A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT_1_A ...
Aminophenpyramine, a derivative of mepyramine (pyrilamine), a typical antagonists of histamine at its H_1 receptor was synthesized and converted into ["1"2"5I]iodoazidophenpyramine, a potential photoaffinity probe for the H_1 receptor. In the dark, reversible binding of this probe to cerebellar membranes occurred with a K/sub d/ of 1.2 x 10"-"1"1 M and a B/sub max/ of 240 fmol/mg of protein and was inhibited by various H_1-receptor antagonists with the expected potencies. These features establish the compound as one of the most potent H_1-receptor antagonists known so far. Upon IV irradiation, 5% of the bound radioactivity was covalently incorporated into cerebellar membrane polypeptides as shown by standard NaDodSO_4/PAGE. Two bands of 47 and 56 kDa were consistently labeled, labeling being prevented by various H_1-receptor antagonists with the expected potencies and ...
Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of functional selectivity ...
Background: Thyroid-stimulating autoantibodies (TSAb) bind to the thyrotropin receptor (TSHR) extracellular domain, or ectodomain (ECD), comprising a leucine-rich repeat domain (LRD) linked by a hinge region to the transmembrane domain (TMD). The LRD (residues 22???260; signal peptide 1???21) contains two disulfide-bonded loops at its N-terminus. In the crystal structure of the isolated LRD complexed with human TSAb monoclonal antibody (mAb) M22, N-terminal disulfide loop 1 (residues 22???30) could not be determined because of crystal disorder. Nevertheless, present crystal structure data are interpreted to exclude a role for the LRD N-terminal disulfide loops in the TSAb epitope(s), contradicting prior functional evidence of a role for these loops in TSAb function. Materials and Methods: ...
Somatostatin receptor scintigraphy (SRS) is a valuable method for the detection of somatostatin receptor-positive lesions. Most gastrinomas (over-)express the somatostatin receptor subtype 2 which can be targeted by In-111 labeled Octreotide. Different studies show a high sensitivity of SRS for the localization and staging of gastrinomas. SRS seems to be superior to other non-invasive imaging modalities and has been proven to significantly contribute to patient management. However, the sensitivity depends on the size and exact localization of the tumors. Smaller lesions and lesions located in the duodenum show a significantly lower sensitivity. In any case, SRS belongs to the routine imaging procedure for gastrinomas for localization and staging and can also be used for evaluation of the tumor progression. (author)
Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot ...
The mechanisms that contribute to the extinction of previously acquired memories are not well understood. These processes, often referred to as inhibitory learning, are thought to be parallel...Full Text Available
Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal and mechanical stimuli in organisms ranging from mammals to Caenorhabditis elegans....Full Text Available
BackgroundGreen tea consumption has been shown to have cancer preventive qualities. Among the constituents of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG)...Full Text Available
Receptor protein tyrosine phosphatase T (PTPRT/PTPρ) is frequently mutated in human cancers including colon, lung, gastric and skin cancers. More than half of the identified tumor-derived...Full Text Available
BackgroundThe dynorphin-kappa opioid receptor (KOR) system regulates glial proliferation after sciatic nerve injury. Here, we investigated its role in cell proliferation following...Full Text Available
Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by...Full Text Available
Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However,...Full Text Available
1. The stereospecificity of the enantiomers of LY253352, a potent and selective alpha 1-adrenoceptor antagonist, were studied in the human prostate and canine brain using radioligand receptor binding...Full Text Available
Cervical spinal cord hemisection rostral to the phrenic nucleus leads to paralysis of the ipsilateral hemidiaphragm in adult rats. Respiratory function can be restored to the paralyzed hemidiaphragm...Full Text Available
[3,5-"3H] 4-Azidoclonidine 6 was prepared from [3,5-"3H] 4-aminoclonidine 4 and has emerged as a valuable tool to study the alpha-2-adrenergic receptor. (author)
Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available
AimsIt is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus.MethodsA...Full Text Available
BackgroundNFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as...Full Text Available
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested...Full Text Available
SummaryTRPV1 is the founding and best-studied member of the family of temperature-activated transient receptor potential ion channels (thermoTRPs). Voltage, chemicals, and heat...Full Text Available
Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated...Full Text Available
The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the...
Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons is central to cognitive psychology. The multiprotein complexes formed by...Full Text Available
Gonadal, adrenal, and thyroid hormones affect the brain directly, and the sensitivity to hormones begins in embryonic life with the appearance of hormone receptor sites in discrete populations of neurons....Full Text Available
Somatostatin receptor expression has been demonstrated on a number of plasma cell lines. Therefore, we questioned whether somatostatin receptor scintigraphy (SRS) can be used to demonstrate in vivo multiple myeloma (MM) activity. SRS was performed in newly diagnosed (n = 9) or relapsing (n = 18) MM patients or in patients with localized plasmacytoma (n = 2). The results were compared with radiographic findings. A positive SRS was demonstrated in 44% of the newly diagnosed patients, in 83% of the relapsed patients and in both patients with plasmacytoma. The SRS findings corresponded with radiographic abnormalities in 40% of the patients. However, in relapsed patients 60% demonstrated increased SRS uptake in areas without new radiographic abnormalities. The positive SRS corresponded with histologically proven disease activity and responded upon treatment. Moreover, immunohistochemical staining of MM material demonstrated concordant somatostatin ...
BackgroundPostoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat...Full Text Available
Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the...Full Text Available
Human epidermal growth factor receptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2...Full Text Available
The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles...Full Text Available
Background:Endothelin-1 may be involved in the development of diabetic microangiopathy. We studied the effect of endothelin-1 blockade on myocardial microcirculation during coronary...Full Text Available
Rejection of eight aldehydes, eight ketones, five secondary alcohols, and 3-pentanol has been studied in the blowfly Phormia regina Meigen. The data agree with results previously reported...Full Text Available
The effect of A1-adenosine receptor antagonism via 8-cyclopentyl-1,3-dipropyl-xanthine (CPDPX) on the stimulation of skeletal muscle glucose uptake by...Full Text Available
PurposeIn our previous studies we showed that upregulating claudin-6 (CLDN6) expression may contribute to preventing breast cancer, and that 17β-estradiol induces a concentration-...Full Text Available
A statistical method is developed to determine the locations of major pollutant sources affecting a distant downwind receptor, provided that air trajectories can be estimated. Probability density functions are estimated which indicate the overall residence time of air parcels over a given geographic region as they travel toward a receptor and residence time for the case of high pollutant concentrations at the receptor. These functions are used to estimate a conditional probability function which indicates the potential for a source region to contribute to high air pollution concentrations. Finally, a source contribution function is formulated to indicate the relative contribution of different source regions to high concentrations at the receptor. The method is tested using data collected at Grand Canyon National Park in 1980. The dominant pathway for air masses arriving at Grand Canyon during this ...
Targeted studies completed include the evaluation of tritiated N-0437, evaluation of "3"5S-cysteamine, evaluation of "1"8F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic receptor ...
Targeted studies completed include the evaluation of tritiated N-0437, evaluation of /sup 35/S-cysteamine, evaluation of /sup 18/F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic ...
In this study we compared the molecular signalling elicited by rexinoids, selective retinoid X receptor (RXR)-activators, in several organs (i.e. liver, kidney,...Full Text Available
BackgroundGlucocorticoids down-regulate cytokine synthesis and suppress inflammatory responses. The glucocorticoid receptor (GR) antagonist RU486 may exacerbate the inflammatory...Full Text Available
Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation....Full Text Available
BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available
Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic...Full Text Available
Hypoxia, or reduced oxygen, occurs in a variety of clinical and environmental situations. Hypoxic exposure is associated with decreased muscle mass and a concomitant reduction in exercise capacity,...Full Text Available
Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic...Full Text Available
Cleavage of membrane-associated proteins with the release of biologically active macromolecules is an emerging theme in biology. However, little is known about the nature and regulation of the involved...Full Text Available
BackgroundZibotentan (ZD4054) is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of prostate cancer. As zibotentan is eliminated...Full Text Available
A parallel bundle of transmembrane (TM) alpha-helices surrounding a central pore is present in several classes of ion channel, including the nicotinic acetylcholine receptor (nAChR). We have modeled...Full Text Available
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression...Full Text Available
Acute inflammation is important for tissue repair; however, chronic inflammation contributes to neurodegeneration in Alzheimer’s disease (AD) and occurs when glial cells undergo prolonged...Full Text Available
IntroductionIn the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones...Full Text Available
Macrophage activation by the proinflammatory cytokine interferon-γ (IFN-γ) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature...Full Text Available
The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated...Full Text Available
Nicotine is the main psychoactive ingredient in tobacco and its rewarding effects are considered primarily responsible for persistent tobacco smoking and relapse. Although dopamine has been extensively...Full Text Available
Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in...Full Text Available
The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on neurological impairment and histologically measured infarction volume...Full Text Available
The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and...Full Text Available
Hypoxia–ischemia (H/I) in the premature infant leads to white matter injury termed periventricular leukomalacia (PVL), the leading cause of subsequent neurological deficits. Glutamatergic...Full Text Available
Myelin-associated glycoprotein (MAG) has been implicated in inhibition of nerve regeneration in the CNS. This results from interactions between MAG and the Nogo receptor and gangliosides on...Full Text Available
The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum...Full Text Available
Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium...Full Text Available
Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction...Full Text Available
Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented...Full Text Available
We had previously identified a macrophage surface protein whose expression is highly induced, transient, and specific, as it is restricted to actively fusing macrophages in vitro and in vivo. This protein...Full Text Available
A growing number of studies suggest that the development of compulsive drug seeking and taking depends on dorsostriatal mechanisms. We previously observed that ex vivo acute...Full Text Available
In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...Full Text Available
Host cells use metabolic signaling through the LXRα nuclear receptor to defend against Listeria monocytogenes infection. 25-Hydroxycholesterol is a natural ligand of LXRs that...Full Text Available
Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor...Full Text Available
Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that...Full Text Available
The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)2 or...Full Text Available
BackgroundThe VP2 outer capsid protein Bluetongue Virus (BTV) is responsible for receptor binding, haemagglutination and eliciting host-specific immunity. However, the assembly of...Full Text Available
Sensory experience plays a crucial role in regulating neuronal shape and in developing synaptic contacts during brain formation. These features are required for a neuron to receive, integrate, and transmit...Full Text Available
Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely...Full Text Available
The endothelin-B (ETB) receptor is a G-protein-coupled receptor that binds endothelin ligands and is essential for the development of epidermal melanocytes and enteric neurons. Recent reports indicate that ETB is localized to nuclei in cardiac ventricular myocytes, although it has been thought that ETB is localized mainly on the plasma membrane. It remains unknown, however, whether this unique distribution of ETB occurs in other tissues. To elucidate the subcellular distribution of ETB in the intestine, we performed immunofluorescence of ETB in mouse intestine using a specific antibody. ETB-like immunoreactivity was detected in both the mucosal and muscle layers. In the mucosal layer, villous epithelial cells, stromal cells of the lamina propria, and cryptic cells were immunostained. Subcellularly, ETB is localized mainly to the nuclei of villous epithelial cells. In the muscle layer, immunoreactivity of ETB was localized to the myenteric ...
Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor and is an attractive angiogenesis target for cancer therapy. In addition to the transmembrane...Full Text Available
Bacillus thuringiensis subsp. israelensis, which is used worldwide to control Aedes aegypti larvae, produces Cry11Aa and other toxins during...Full Text Available
This study addresses the mechanism of transport of the H2-receptor antagonist, cimetidine, by the human placenta. A 4-h recycling perfusion of a single placental cotyledon of normal, term, human placenta...Full Text Available
Histamine has been proposed to be an important regulator of energy intake and expenditure. The aim of this study was to evaluate histamine regulation of glucose and lipid metabolism and development...Full Text Available
Recently, we demonstrated that the central ghrelin signalling system, involving the ghrelin receptor (GHS-R1A), is important for alcohol reinforcement. Ghrelin targets a key mesolimbic circuit involved...Full Text Available
Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally-induced expression of neuronal plasticity utilizes an NMDAR-dependent,...Full Text Available
The genetic basis of odorant-specific variations in human olfactory thresholds, and in particular of enhanced odorant sensitivity (hyperosmia), remains largely unknown. Olfactory receptor (OR) segregating...Full Text Available
The role of pheromone biosynthesis activating neuropeptide (PBAN) in the regulation of pheromone biosynthesis of several female moth species is well elucidated, but its role in the males has been a...Full Text Available
Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent...Full Text Available
Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement...Full Text Available
Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM...Full Text Available
Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull,...Full Text Available
BackgroundLeukotrienes (LTs) belong to the large family of lipid mediators implicated in various inflammatory conditions such as asthma and rheumatoid arthritis. Four distinct types...Full Text Available
SUMMARYMotile dendritic filopodial processes are thought to be precursors of spine synapses, but how motility relates to cell-surface cues required for axon-dendrite recognition...Full Text Available
Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S....Full Text Available
BackgroundThiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARγ) and are used clinically to help restore peripheral insulin sensitivity...Full Text Available
Porphyromonas gingivalis has been implicated as a causative pathogen in periodontitis. Immunotherapeutic approaches have recently been suggested to aid in the clearance of P....Full Text Available
The specific receptor sites and the endocytosis of transferrin (Tf) are evidenced in a cell line (HT-29) derived from a human colic adenocarcinoma by means of "1"2"5I radiolabeled Tf. The receptor density is studied in undifferentiated (UD) or differentiated (D) cells with respective doubling times of about 24 hours and 46 hours. The number of binding sites for Tf is 162,000 (K_d = 7.8 nmol/l in ND cells and 68,000 (K_d = 7.40 nmol/l) in D cells. The distribution between the Tf bound to the cell surface and the internalized Tf is investigated by elimination of Tf bound to the surface by an acid wash method. The intracellular cycle of Tf seems to be characterized by a slower kinetics in UD cells. The high density of Tf receptor sites in HT-29 UD cells should allow the detection or the treatment of highly evolutive colic adenocarcinoma by means of Tf.
Objective:To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical.Methods:Experimentally:...Full Text Available
B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated...Full Text Available
Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma,...Full Text Available
BackgroundThe N-methyl-D-aspartate (NMDA)-type glutamate receptor expressed at excitatory glutamatergic synapses is required for learning and memory and is critical for normal brain...Full Text Available
Retinoic acid inducible gene I (RIG-I) is a pattern recognition receptor (PRR) responsible for detection of nucleic acids from pathogens in the cytoplasm of infected cells and induction of type I interferon...Full Text Available
SummaryHuman skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1...Full Text Available
We investigated the effects of PSARK∷IPT (for Senescence-Associated Receptor Kinase∷Isopentenyltransferase) expression and cytokinin production...Full Text Available
Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions...Full Text Available
BackgroundMost rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen...Full Text Available
Mechanisms regulating sexual differentiation of the zebra finch song system appear to include both genetic and hormonal factors. Sorting Nexin 2 (SNX2), which is involved in trafficking proteins...Full Text Available
We presented data showing that the CART-19 cells expressing the 4-1BB signaling domain can have unprecedented and massive in-vivo expansion, traffic to tumor sites, persist long term in vivo, and induce...Full Text Available
Cytokinins are distributed through the vascular system and trigger responses of target cells via receptor-mediated signal transduction. Perception and transduction of the signal can occur at the plasma...Full Text Available
Cd36 is a small-molecular-weight integral membrane protein expressed in a diverse, but select, range of cell types. It has an equally diverse range of ligands and physiological functions, which has...Full Text Available
Klebsiella pneumoniae is able to grow anaerobically with citrate as a sole carbon and energy source by a fermentative pathway involving the Na+-dependent citrate...Full Text Available
Benzodiazepine withdrawal anxiety is associated with potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) currents in hippocampal CA1 pyramidal...Full Text Available
Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based...Full Text Available
Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole...Full Text Available
The pharynx is the primary reservoir for strains of group A Streptococcus (GAS) associated both with pharyngitis (streptococcal sore throat) and with invasive or “flesh-eating”...Full Text Available
BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available
Bacterial pathogens use virulence strategies to invade epithelial barriers, but active processes of epithelial cells may also contribute to the endocytosis of microbial particles. To focus on the latter,...Full Text Available
AIM: To investigate atrial natriuretic peptide (ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A) pathway and diabetic gastroparesis.METHODS:...Full Text Available
Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our...Full Text Available
Pharmacologic or genetic deletion of components of the renin-angiotensin system leads to postnatal kidney injury, but the roles of these components in kidney development are unknown. To test the hypothesis...Full Text Available
Numerous xenobiotics, including therapeutics agents, are substrates for bioactivation to electrophilic reactive intermediates that may covalently modify biomolecules. Selective estrogen receptor...Full Text Available
BackgroundMale infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding...Full Text Available
We sought to determine the effects of activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male...Full Text Available
Endogenous immune complexes present in sera from 10 different patients with systemic lupus erythematosus (SLE) in an active phase were allowed to bind to Raji cells; the ability of intact complement...Full Text Available
BackgroundCentrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation...Full Text Available
The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian...Full Text Available
ObjectiveThe goal of the study was to investigate the genetic and molecular basis of a novel syndrome of marked hyperglucagonemia and pancreatic α cell hyperplasia...Full Text Available
BackgroundThis in vitro study was conducted to compare the accuracy of two digital image receptors in identifying the location of tip of a fine endodontic file and radiographic apex...Full Text Available
ABSTRACT: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor ?/? (PPAR?/?) and PPAR?. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.See related research article: http://genomebiology.com/2011/12/8/R75. PMID:21861850
Resistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. Several genetic polymorphisms in pattern recognition receptors, most remarkably Toll-like receptors (TLRs), have been described to influence resistance and tolerance to aspergillosis in distinct clinical settings. TLRs on dendritic cells pivotally contribute in determining the balance between immunopathology and protective immunity to the fungus. Epithelial cells also contribute to this balance via selected TLRs converging on indoleamine-2,3-dioxygenase (IDO). Studies in experimental hematopoietic transplantation confirmed the dichotomy of pathways leading to resistance and tolerance to the fungus providing new insights on the relative contribution of the hematopoietic/nonhematopoi...
Serotonin is one of the neurotransmitters found in the brain and mediates brain functions. It is very well known that serotonin related brain abnormalities are exerted mainly via serotonin receptors in a similar manner to other neurotransmitters found in the brain. Recently, it has also been found that serotonin is involved in Alzheimer's disease either directly or indirectly by its actions on serotonergic neurons. To understand and treat the diseases caused by abnormalities in the serotonergic system in the brain, it is certain that its mechanism of function has to be well investigated. So far several 5-HT receptors and receptor subtypes have been well characterized. Moreover, serotonin agonists and antagonists acting on specific receptors are chemically synthesized and are now available for the prevention or treatment of serotonergic related diseases. In recent years, a great demand for developing ...
Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios.
This study describes the chemical composition of the essential oil of Artemisia maritima (Am.Oil) and the pharmacological basis for its medicinal use in gut and airways disorders. Twenty five compounds, composing 93.7% of the oil, were identified; among these, chrysanthenyl propionate and elixene were identified for the first time from any Artemisia species. The Am.Oil (0.3?1.0 mg/mL) suppressed spontaneous and high K+ (80 mM)-induced contractions in isolated rabbit jejunum, suggestive of an antispasmodic effect mediated possibly through calcium channel blockade. The calcium channel blockade activity was confirmed when pre-treatment of the tissue with Am.Oil (0.01?0.03 mg/mL) shifted the Ca++ concentration-response curves to the right, similar to verapamil and papaverine. In isolated trach...
It was developed a new formulation of macro aggregates of Samarium 153 ({sup 153} Sm-MH) for the arthropaties treatment. The radio pharmaceutic was prepared by reaction of Samarium 153 chloride (SmCl{sub 3}) in aqueous environment with sodium boron hydride in NaOH 0.5 N. The microscopic analysis shown that the particles have an average size of 4% m (range 1-14 {mu} m). The velocity of sedimentation was 0.008 cm/min with high stability in vitro in human serum. The biological studies in healthy rabbits, shown that the complex is retained inside the articulation still eight days after of the administration of the radiopharmaceutical. Likewise, it is presented the data of absorbed dose in the different target organs, which was determined by thermoluminescent dosimetry (TLD) through the use of a REMCAL phantom (radiation equivalent manikin calibration). (Author)
Neutron energy spectra were measured for two OSURR experimental facilities. The method of multiple foil activation was used with the SAND-II neutron spectrum unfolding code to obtain spectral data for the Central Irradiation Facility and Rabbit tube. Limited data was obtained for the thermal column using only gold foils. Calculations were made of the neutron environment in various locations using the MORSE code. A shift towards higher neutron energies was observed comparing results for LEU and HEU cores. A slight loss in total thermal neutron flux was measured for all positions. Calculational results show reasonable agreement with measured data.
Aim:To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone.Methods:Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells.Results:Tachyarrhythmia produced by isoprenaline (15 ?mol/L) could be reversed by sophocarpine (300 ?mol/L). Sophocarpine (10 ?mol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (Vmax) of the fAP by 24.4%...
Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg/sup 2 +/ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.
In FY1994, JMTR was in operation during 4 operation cycles with low enriched Uranium(LEU,20%) fuel for irradiation study of nuclear fuels and materials and for radioisotope production. Irradiation studies were carried out using capsules, Oarai Gas Loop-1(OGL-1), Oarai Shroud Facility(OSF-1) and hydraulic rabbits irradiation facilities in support of LWR, FBR, HTTR and thermonuclear reactor. Irradiation studies on blanket materials were intensively carried out. Power ramping tests were carried out and the future program is under consideration. For R and D works, neutron spectrum evaluation technology, re-instrumentation technique for irradiation fuel rod, remote controlled SEM apparatus and examination technique with miniaturized specimens were successfully developed. (author).
Techniques of chemical analysis, amino acid sequencing and autoradiography are being used to study the frequency of incorporation of normally noncoded amino acids into hemoglobins and seminal fluid proteins. We are studying, by the sequencing of radiolabeled proteins followed by the recovery of ["3H] isoleucine phenylthiohydantoin by high-performance liquid chromatography, the frequency at which normally noncoded isoleucine is incorporated into hemoglobin because of base-substitution mutations versus translational errors. Irradiation increases the isoleucine content of human hemoglobin and the frequency of substitution of isoleucine for specific amino acids in rabbit hemoglobin. Studies to date indicate that these techniques have been developed sufficiently for initial analysis of the potential of drugs and environmental pollutants to induce base-substitution mutations in mammalian somatic cells.
Transparency is essential for normal corneal function. Recent studies suggest that corneal cells express high levels of so-called corneal crystallins, such as aldehyde dehydrogenase (ALDH) and transketolase (TKT) that contribute to maintaining cellular transparency. Stromal injury leads to the appearance of repair phenotype keratocytes, the corneal fibroblast and myofibroblast. Previous studies on keratocytes from species such as bovine and rabbit indicate that the transformation from the normal to repair phenotype is accompanied by a loss of corneal crystallin expression, which may be associated with loss of cellular transparency. Here we investigated if a similar loss occurs with human keratocyte repair phenotypes. Human corneal epithelial cells were collected by scraping and keratocytes...
The possibilities for therapy in the field of severe cardiac insufficiency have been extended in recent years by the introduction of novel agents endowed with a positive inotropic action. These substances may be arranged in two large classes: sympathomimetic agents and "non sympathomimetic--non digitalis-like" inotropic agents. The stimulant action of noradrenaline, adrenaline and isoproterenol on beta-adrenergic myocardial receptors has been clearly demonstrated but the usefulness of these medicines is limited by their positive chronotropic and arrhythmogenic actions. Dopamine and dobutamine have proved to be very useful in the treatment of patients in intensive care units. However, the exclusively intravenous route of administration limits their importance to the medium or long term. Several compounds, which are active by the oral route, have been the subject of therapeutic trials for the short or medium term. The problems posed by their use result, in the first ...
PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles and parafollicular C-cells. A high ...
Screening of a human placenta lambdagt11 library has led to the isolation of the cDNA for the human ..beta../sub 1/-adrenergic receptor (..beta../sub 1/AR). Used as the probe was the human genomic clone termed G-21. This clone, which contains an intronless gene for a putative receptor, was previously isolated by virtue of its cross hybridization with the human ..beta../sub 2/-adrenergic receptor (..beta../sub 2/AR). The 2.4-kilobase cDNA for the human ..beta../sub 1/AR encodes a protein of 477 amino acid residues that is 69% homologous with the avian ..beta..AR but only 54% homologous with the human ..beta../sub 2/AR. This suggests that the avian gene encoding ..beta..AR and the human gene encoding ..beta../sub 1/AR evolved from a common ancestral gene. RNA blot analysis indicates a message of 2.5 kilobases in rat tissues, with a pattern of tissue distribution consistent with ..beta../sub 1/AR binding. This pattern is quite ...
In this study, we measured the effects of different concentrations of paraquat (0,01 mM and 1,0 mM) on the 1-"1"4CO_2 and 6-"1"4CO_2 production of rabbit lung slices and isolated alveolar macrophages, in 20% and 95% oxygen phases respectively. A 95% oxygen phase induced an increase in the 6-"1"4C-glucose oxidation of control lung slices over a 3-hour period, while the increased activity of the pentose pathway over the first 2 hours started to decline during the third hour of incubation. Paraquat (1,0mM) in 20% oxygen caused a consistent increase in the 6-"1"4CO_2 production by lung slices, but in a 95% oxygen phase gradually inhibited the 6-"1"4C-glucose oxidation over a period of 3 hours. The pentose phosphate pathway was highly significantly stimulated by 1,0 mM paraquat in 20% and 95% oxygen over 3 hours. When isolated alveolar macrophages (viability 95%) were incubated in a 20% and 95% oxygen phase respectively, both the 6-"1"4C-glucose and 1-"1"4C-glucose ...
A portion of the active site of rabbit skeletal myosin near the ribose ring of ATP can be labeled by the photoaffinity analogue 3{prime}(2{prime})-O-(4-benzoylbenzoyl)adenosine triphosphate (Bz{sub 2}ATP). The specificity of the photolabeling was assured by first trapping ({sup 14}C)Bz{sub 2}ATP at the active site by use of thiol cross-linking agents. Five radioactive peptides were isolated by high-performance liquid chromatography after extensive trypsin and subtilisin digestion of photolabeled myosin subfragment 1. Four of these peptides were sequenced by Edman techniques, and all originated from a region with the sequence Gly-Glu-Ile-Thr-Val-Pro-Ser-Ile-Asp-Asp-Gln, which corresponds to rabbit myosin heavy chain residues 312-328. The fifth labeled peptide had an amino acid composition appropriate for residues 312-328. Amino acid composition, radiochemical analysis, and sequence data indicate that Ser-324 is the major amino acid residue ...
(Materials and Methods) (I) VX/sub 2/ carcinoma was transplanted to the rabbit tibia, sup(99m)Tc-MDP was intravenously injected when bone destruction was radiologically seen. Preoperative scintigraphs, postoperative one of the resected tibia and fibra and scintigraphs of sliced tumor were compared with each other. Tissue fragments were collected from the sliced tumor, and RI was measured to compare concentration rates at different parts together with histological investigations. (II) Tetracycline was given to the rabbit of Experiment (I) to compare with the concentration of sup(99m)Tc-MDP. (III) Microautoradiography method was done on the experimental animals for investigation of the concentration of sup(99m)Tc-MDP. (Results) (I) Localization of sup(99m)Tc-MDP was increased at the sites of tumorous bone formation, of reactive bone formation at tumor edges, and of cartilage calcification, with little concentration at tumor cells or necrotic ...
Tc-MDP 10mCi was intravenously given preoperatively to 20 patients with primary bone tumors and 1 with a metastatic bone tumor. Preoperative and postoperative scintigraphs of resected tumor and scintigraphs of sliced tumor were compared. Tissue fragments were collected from the sliced tumor, and RI measured to compare concentration rates at different areas. Histological investigations were also done. Localization of Tc-MDP was increased at sites of tumorous bone formation, of reactive bone formation at tumor edges, and of cartilage calcification, with little concentration at tumor cells or necrotic tissue. VX/sub 2/ carcinoma was transplanted into the rabbit tibia, Tc-MDP was intravenously injected when bone destruction was radiologically evident, and investigations were done as in the clinical cases. In experimental bone tumor, increased uptake localization of Tc-MDP was much the same as in clinical cases. Tetracycline was given to the rabbit ...
Previous in vitro studies have demonstrated that Ho:YLF laser is capable of inducing physical and chemical changes on dental surfaces treated for caries prevention. The temperature in the pulp chamber was in vitro evaluated to as a function of the power and frequency of the laser irradiation. The purpose of this work is to verify the occurrence of pulp inflammation after Ho:YLF laser irradiation using different parameters in rabbits' teeth. The premolars and molars of ten rabbits (NZB) were divided in two groups according to the irradiation energy values of a Ho:YLF laser prototype operating at 2.065{mu}m wave length, frequency of O,5Hz and pulse length of 250{mu}s. An group A teeth were irradiated with using ten pulses of 334mJ/pulse of a Ho:YLF laser prototype operating at O.5Hz, and group B, with 512mJ/pulse. Animals were killed by transcardiac perfusion and the samples were prepared for histopathological analysis. The in vitro ...
In 65 adult rabbits of both sexes (2.5 to 6 kg) the following salvaging procedures were performed after simulated trauma: (1) Continuous suture line; (2) closure with fibrin sealant after temporary clamping; (3) hemisplenectomy with omental wrap; (4) suture fixation of fragments and slices of spleen tissue to the peritoneum; (5) suture fixation of spleen fragments to the omentum; (6) extraperitoneal subcutaneous transposition of spleen cubes. In addition, the likelihood of spontaneous splenosis was examined in a preliminary study involving 5 animals by introducing unattached spleen meal and fragments. Scanning was repeated 4 to 12 weeks postoperatively. The functional competence of minor parenchymal islands was also investigated with well counter measurements of organ and muscle tissue homogenates. Spontaneous splenosis after abdominal injuries was not found to be the rule. Salvaging procedures at the natural vascular hilus by sutures, fibrin sealant and ...
The affinity label 8-((4-bromo-2,3-dioxobutyl)thio)adenosine 5{prime}-triphosphate (8-BDB-TA-5{prime}-TP) reacts covalently with rabbit muscle pyruvate kinase, incorporating 2 mol of reagent/mol of enzyme subunit upon complete inactivation. Protection against inactivation is provided by phosphoenolpyruvate, K{sup +}, and Mn{sup 2+} and only 1 mol of reagent/mol of subunit is incorporated. The authors have now identified the resultant modified residues. After reaction with 8-BDB-TA-5{prime}-TP at pH 7.0, modified enzyme was incubated with ({sup 3}H)NaBH{sub 4} to reduce the carbonyl groups of enzyme-bound 8-BDB-TA-5{prime}-TP and to introduce a radioactive tracer into the modified residues. Following carboxymethylation and digestion with trypsin, the radioactive peptides were separated on a phenylboronate agarose column followed by reverse-phase high-performance liquid chromatography in 0.1% trifluoroacetic acid with an acetonitrile gradient. Gas-phase sequencing ...
We have done analysis of elements in the Baltic sea sediment by using gamma spectrometry in neutron activation analysis Goal of the analysis is to determine the rate of morsel elements which is contained in the Baltic sea sediment. Sample of the Baltic sea Sediment (IAEA-SED-1), Standard of Reference Material (SRM) 1646 Estuarine Sediment and Standard Ce, Fe, Sc, and Co are put into vial of capsule rabbit, then irradiated together for 30 minutes in rabbit facility Multi Purpose Reactor at power of 25 MW and then cooled for one week. Next sample, standard, and SRM which have irradiated, each is cut for 30 minutes using gamma spectrometer. Result of analysis of rate of elements Ce, Fe, Sc and Co in the baltic sea sediment successively equal to 141.20 ppm, 5.91 %, 14.88 ppm, and 19.59 ppm. Result of analysis in SRM Estuarine sediment successively equal to 96.60 ppm, 3.21 %, 10.25 ppm, and 9.63 ppm. Result of this analysis if compared to the value ...
Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than ...
..cap alpha..-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant ..cap alpha..-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the ..cap alpha..-2 receptors, labeled with the agonist (/sup 3/H)para-aminoclonidine, verified the concept that ..cap alpha..-2 receptors are closely associated with adrenergic nerve terminals and that ..cap alpha..-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since ..cap alpha..-2 agonists can influence sympathetic outflow, ..cap alpha..-2 binding sites were closely analyzed in the intermediolateral cell column of the ...
It is now known that various growth factors may also act in the central nervous system. Among them, it has recently been shown that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) may possess trophic effects in the mammalian brain. We report here on the respective autoradiographic distribution of ["1"2"5I]EGF and ["1"2"5I]IGF-I receptor binding sites in the rat brain, both during ontogeny and in adulthood. It appears that ["1"2"5I]EGF sites are mostly found in the rat forebrain during brain development. On the other hand, ["1"2"5I]IGF-I sites are more widely distributed both during ontogeny and in adulthood. These results reveal the plasticity of the expression of EGF and IGF-I receptor sites in the mammalian brain. This could be relevant for the respective role of these two growth factors in the development and maintenance of neuronal function.
The synthesis of (1',3'-{sup 3}H)4-(4'-azido-5',6',7',8'-tetrahydro-5'5'8',8'-tetramethyl-2'-anthracenyl)benzoic acid is described. This retinoid was designed as a photoaffinity probe of the receptor sites of cellular retinoic acid-binding protein and the nuclear retinoic acid receptor protein. The ({sup 3}H)azidoretinoid was prepared from 1,2,3,4-tetrahydro-1,1,4,4-tetra-methyl-7-(4-methylphenyl)-5-nitroanthracene in five steps in 15% yield (89% radiochemical purity by HPLC). {sup 1}H and {sup 3}H NMR was used to confirm the sites of {sup 3}H substitution on the ring. (author).
The measurement of physiological parameters in man is possible with the help of positron emission tomography (PET) and radiopharmaceuticals labeled with short lived positron emitters as C 11, N 13, O 15 and F 18. With the use of this substances it is possible to make a tomographic map defining regional metabolic parameters in normal and diseased brain. This technique has therefore also be named 'in vivo autoradiography'. The possibility of applying C 11 or F 18 labeled deoxyglucose with PET for detecting regional and local changes in cerebral metabolic rate of glucose in brain development in children of 5 days to 1 year of age is discussed. Beyond this a relationship between cerebral metabolic rate of glucose, cerebral blood flow and cerebral metabolic rate of oxygen by use of this technique after inhalation of O 15 and C 11-labeled CO_2 is shown. Attention is drawn to the application of C 11-methyl-spiperone and PET to visualize dopamine receptor density in the ...
Aims: Serotonin (5-hydroxytryptamine 3; 5-HT3) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT3 antagonists are part of the `gold standard' antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT3 receptor subunit genes with the occurrence of CINV. Materials & methods: A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT3 receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis. Results: A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assu...
A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. All three peptides are cleared by the natriuretic peptide-C receptor and degraded by the ectoenzyme neutral ...
This progress report covers period from Nov. 1, 1989 to Aug. 31, 1990. The long term objective was to develop receptor-binding radiotracers for SPECT or PET imaging of CNS or peripheral nervous system. The specific chemistry aims, as understood on the basis of past findings, were: to synthesize and develop a more polar analogs of 4IQNB, possessing similar binding characteristics but eliminated more rapidly from the surrounding tissues and the target organ, to design a method of introducing a technetium chelating group onto a molecule or cholinergic agent without drastic lowering of its apparent affinity, to synthesize and develop radiotracers based on m-AChR antagonists selective for one of the subtypes of the receptor. The chemistry service aims were to prepare and characterize (R,R)- and (R,S)-4IQNB and derivatives, to provide the triazene intermediate to other investigators, and to provide ({sup 123}I)4IQNB for in vivo imaging. The ...
Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal solution formulation, whereas oral ...
We report the isolation of cDNA clones for the mouse {alpha}7 neuronal nicotinic acetylcholine receptor subunit (gene symbol Acra7), the only nicotinic receptor subunit known to bind a-bungarotoxin in mammalian brain. This gene may have relevance to nicotine sensitivity and to some electrophysiologic findings in schizophrenia. The mouse {alpha}7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences. The {alpha}7 gene was mapped to mouse chromosome 7 near the p locus with the following gene order from proximal to distal: Myod1-3.5 {+-}1.7 cM-Gas2-0.9 cM {+-} 0.9 cM-D7Mit70-1.8 {+-} 1.2 cM- Acra7-4.4 {+-}1.0 cM-Hras1-ps11/Igf1r/Snrp2a. The human gene was confirmed to map to the homologous region of human chromosome 15q13-q14. 26 refs., 3 figs.
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a ...
Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...
Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater struct...
Abstract Toll-like receptor 2 (TLR2) is an immune sensor for gram-positive bacterial cell wall components. Single-nucleotide polymorphisms (SNPs) in the TLR2 gene that impair its function may, therefore, influence the risk and outcomes of gram-positive bacterial infections. In a cohort of 694 liver transplant recipients, we assessed the TLR2 SNP that is translated into an amino acid substitution of arginine for glutamine at position 753 (R753Q), and we found that its presence was associated with the clinical characteristics and outcomes of gram-positive bacterial infections. The proportions of patients with the TLR2 R753Q SNP did not significantly differ between those with gram-positive bacterial infections and those without gram-positive bacterial infections (9.6% versus 9.6%, P = 0.999)....
Rationale Receptor occupancy study has been performed to evaluate pharmacokinetic profiles in new antipsychotic drug development. While these findings highlight the value of positron emission tomography (PET) for dose-finding study, what is unclear is if it is necessary to conduct these studies in patients with schizophrenia or whether studies in healthy volunteers are adequate. Objectives To determine if it is necessary to conduct dopamine receptor occupancy studies in patients with schizophrenia or whether studies in healthy volunteers are adequate for dose-finding study, we compared the concentration?occupancy relationship in terms of EC50 between patients and healthy volunteers. Methods Ten healthy volunteers and eight patients with schizophrenia participated in the study. We measured ...
A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...
The T cell receptor is a fundamental mediator of the adaptive immune responses, since TR ab on T cells recognize foreign structures (peptides derived from processed antigens) bound to the major histocompatibility complex (MHC) on APC cells. In the present study, we report the cloning of six TRB chains cDNA sequences from gilthead sea bream (Sparus aurata), a fish of high economical impact in South Mediterranean aquaculture. The V-BETA domains have the canonical features of known teleost and mammalian TR V-BETA domains and have been divided in four different subgroups. A multiple alignment of the six sea bream TRB chains with other known TRB sequences was assembled and showed the conservation of the four cysteine residues involved in disulphide bonds and of some amino acids with an importan...
Endogenous opioid peptides (EOP) are molecules affecting many biological functions influencing productive and reproductive performance. They increase in stress conditions and interact with specific opioidergic receptors (OR): delta, kappa and mu. Several studies in other animal species suggest that they can also affect sperm cell motility. In fish the ionic external environment modulates the increase of intracellular calcium ion that is required to activate sperm motility after spawning. In mammals OR are functionally associated to calcium channels and in fishes calcium is highly required for fish sperm activation. In this study the presence of OR on spermatozoa of two Perciform fish, the sharpsnout seabream (Diplodus puntazzo, family Sparidae) and the European sea bass (Dicentrarchus labr...
Intervertebral disc (IVD) cell apoptosis has been suggested to play an important role in promoting the degeneration process. It has been demonstrated that IVD cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic reticulum (ER) pathway. Our study aimed to explore the relationship among these three pathways and grade of IVD degeneration (IVDD). IVDs were collected from patients with lumbar fracture, vertebral tumor, disc herniation or spondylolisthesis. IVDs were distinguished by MRI and histomorphological examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore, the correlation between apoptosis pathways biomarkers and disc pathology were analyzed. Nucleus pulpo...
Fgf receptor 2c (Fgfr2c) was expressed in mature adipocytes of mouse white adipose tissue (WAT). To examine the role of Fgfr2c in mature adipocytes, we generated adipocyte-specific Fgfr2 knockout (Fgfr2 CKO) mice. The hypertrophy impairment of adipocytes in the mesenteric WAT but not in the subcutaneous WAT and decreased plasma free fatty acid (FFA) levels were observed in Fgfr2 CKO mice. Although the expression of genes involved in adipocyte differentiation and lipid metabolism in the mesenteric WAT was essentially unchanged, the expression of uncoupling protein 2 potentially involved in energy dissipation was significantly increased. Among potential Fgf ligands for Fgfr2c, Fgf9 was preferentially expressed in the mesenteric WAT. The present findings indicate that Fgfr2c potentially activ...
Aberrant amyloid-b peptide (Ab) accumulation along with altered expression and function of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery that Ab is bound to a7 nAChRs under many experimental settings, including post-mortem AD brain, much effort has been expended to understand the implications of this interaction in the disease milieu. This research update will review the current literature on the a7 nAChR-Ab interaction in vitro and in vivo, the functional consequences of this interaction from sub-cellular to cognitive levels, and discuss the implications these relationships might have for AD therapies.
C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid to regulation of the ANP and BNP genes. CNP expression in vitro is regulated by TGF-b and recepto...
Previous studies from this laboratory have shown that certain N-substituted phthalimides (NSPs) exhibit GA-like activity in a range of specific bioassays and that bioactive NSPs compete with ({sup 3}H)-GA{sub 4} for soluble binding sites in cucumber homogenates. As such, these compounds may prove useful in the purification and characterization of GA receptor proteins. To this end, five azido-NSPs have been synthesized and are currently being screened for biological activity and photochemical stability. Three azido-NSPs elicit {alpha}-amylase production in barley half-seeds and stimulate tissue elongation in d{sub 5} maize, lettuce, sunflower, and soybean. Further evaluations are in progress and these data as well as the utility of these compounds as photo-affinity ligands will be discussed.
Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to "2"3"9PuO_2- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)
DNA methylation is considered as a potential cause of aberrations in regulation of gene expression during carcinogenesis. Therefore, changes in DNA methylation patterns may be targets for chemoprevention. In the present study, we investigated effects of all-trans retinoic acid (ATRA), vitamin D3, and resveratrol alone and in combination with adenosine analogues: 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-d-arabinosyl-2-fluoroadenine (F-ara-A), on methylation and expression of retinoic acid receptor beta 2 (RARbeta2) in MCF-7 and MDA-MB-231 breast cancer cell lines. Alterations in methylation and expression levels after treatment of cells with the tested compounds were evaluated by methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. RARbeta2 promoter in the ...
The gene encoding the human type I pituitary adenylate cyclase activating polypeptide receptor (ADCYAP1R1) was mapped to chromosome 7 by PCR analysis of genomic DNA from a human/rodent somatic cell hybrid mapping panel. This assignment was confirmed and the gene localized to chromosome band 7p14 by fluorescence in situ hybridization. A yeast artificial chromosome containing ADCYAP1R1 was identified in the CEPH {open_quotes}B{close_quotes} Mega-YAC library. This YAC includes two highly polymorphic dinucleotide repeat sequences that will facilitate genetic studies of the contribution of ADCYAP1R1 in disease states of the central nervous and neuroendocrine systems. 13 refs., 1 fig.
The authors have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative {alpha} subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH{sub 2}-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hydrophobic transmembrane region, and a positively charged cytoplasmic tail. The human and rat {alpha} subunits share an overall homology with one another and the immunoglobulin gene family, suggesting that they arose from a common ancestral gene and continue to share structural homology with their ligands. In addition, the rat gene is transcribed into at least three distinct forms, each of which yields a somewhat different coding sequence.
Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding.
Gonadal hormones modulate neurogenesis in the dentate gyrus differentially in male and female adult rodents. Neurogenesis is comprised of at least two components: cell proliferation (the production of new cells) and cell survival (the number of new neurons that survive to maturity). Previous studies have found sex differences in the level of cell proliferation in the dentate gyrus only when comparing females in a high estrogen state to males. This review focuses on the effects of acute and chronic levels of estrogens or androgens on hippocampal neurogenesis in the adult male and female rodent. Evidence is also reviewed for the co-localization of androgen receptors and estrogen receptors (ER) with markers for cell proliferation or immature new cell survival. Briefly, evidence suggests that ...
The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit (/sup 3/H)diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.
BACKGROUND Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARb) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells. METHODS In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARb and PDLIM4 promoters. Forced Myc overexpression inhibited the RARb and PDLIM4 expression. RESULTS Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2prime-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARb and PDLIM4. CONCLUSION The epigenetic r...
Results in this study are consistent with those of Murdock and his colleagues who clearly demonstrated that clonidine, an agonist of octopaminergic receptors in some insects, significantly increases sucrose feeding. Their studies, however, did not examine the effect of clonidine on protein feeding. Injection of a 20mg/ml/fly dose of clonidine significantly reduces protein feeding in both sexes of Phormia regina, instead of stimulating feeding as is observed with carbohydrate feeding. The manner in which the flies are fed prior to starvation and the method of testing influences the amounts of diet consumed. It is proposed that the biogenic amines influence the state of hunger (i.e., protein versus carbohydrates) while other chemicals and neural mechanisms (i.e., such as sulfakinins and stre...
In many species social behaviors are dependent on integration of chemosensory and hormonal cues. Many chemosensory stimuli are detected by the vomeronasal organ, which projects to many regions that contain steroid receptors, including the medial amygdala. In male hamsters, testosterone is known to acutely increase in response to chemosensory stimulation, and can facilitate sexual behavior by direct action within the medial amygdala. Conspecific stimuli activate the anterior (MeA) and posterior (MeP) medial amygdala, while heterospecific stimuli activate only MeA. Chemosensory stimuli with different social significance differentially activate the dorsal and ventral subdivisions of MeA and MeP. Therefore, it is likely that steroids differentially facilitate stimulation of the medial amygdala...
Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the ?-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antag...
Active oxygens produced by low-dose irradiation can induce the synthesis of proteins involved in the active oxygen reduction path and can activate the chemical self-defense mechanisms in vivo, which can alleviate the injuries caused by active oxygens themselves. The following findings suggests that it is not only by low-dose irradiation that can induce the responses described above but also by any physical and/or chemical stresses which can produce small amount of active oxygens in vivo. 1. X-irradiation with 0.5 Gy and/or water immersion and restraint induced heat shock protein (HSP)70 in rat stomach cells. HSP70 was also induced in adrenal cells by paraquat administration. 2. The SOD activity in pancreas of rat significantly increased by #gamma#-irradiation with 0.5 Gy. 0.5 Gy irradiation preceeding the alloxan administration significantly suppressed the increase in pancreatic lipid peroxides and in blood glucose levels, degranulation in #beta# cells, and decrease in blood insulin ...
The effects of 0.2 and 0.5 mL/kg Innovar (a neuroleptic analgesic) on cardiovascular functions and reflexes in rabbits were measured. We recorded the effects of Innovar on arterial pressure, heart rate, respiration rate, ventricular contractility, arterial oxygen tension, as well as the drug's effects on the bradycardia and vasoconstrictor response to cigarette smoke stimulation of the nose (the so-called "nasopharyngeal reflex"). In animals given 0.2 mL/kg Innovar, all steady state cardiovascular variables had returned to pre-Innovar levels in 45 min, as had the efficacy of the nasopharyngeal reflex. In animals given 0.5 mL/kg Innovar, all steady state cardiovascular variables, except PaO2, were slightly but significantly depressed for up to 135 min after injection. The nasopharyngeal reflex returned to normal within 90 min. Because of the calmative and analgesic effects of Innovar, and its only moderate effects on cardiovascular functions and reflexes, we feel it ...
The Ohio State University Research Reactor (OSURR) is licensed to operate at a maximum power level of 500 kW. A pool-type reactor using flat-plate, low enriched fuel elements, the OSURR provides several experimental facilities including two 6-inch i.d. beam ports, a graphite thermal column, several graphite-isotope-irradiation elements, a pneumatic transfer system (Rabbit), various dry tubes, and a Central Irradiation Facility (CIF). The core arrangement and accessibility facilitates research programs involving material activation or core parameter studies. The OSURR control room is large enough to accommodate laboratory groups which can use control instrumentation for monitoring of experiments. The control instrumentation is relatively simple, without a large amount of duplication. This facilitates opportunities for hands-on experience in reactor operation by nuclear engineering students making reactor parameter measurements. For neutron activation analysis and ...
Intramuscular hermorrhage was induced by injecting autologous blood into the paraspinal muscle of 8 rabbits. In order to evaluate the time-dependent changes of hemorrhage observed on MRI, the animals were imaged at different stages of blood resolution at 0.02 tesla (T), and control examined with ultrasound using a 7.5 MHz linear transducer. Six inversion recovery sequences (TR=1 000 ms. TE=30 ms, and TI=18, 48, 148, 201, 302, and 398 ms) were used for the invivo calculation of T1 relaxation times. IR 1 000 (398)/30 imaging was performed before and after the Gd-DOTA administration. The hemorrhage was evident on MR images throughout the study, especially on the T2 weighted (SE 1 000/100) images. MRI showed the healing lesion longer than ultrasound. The T1 relaxation time increased during the time of resolution. Lesions on days 4 to 7 enhanced in intensity after the injection of Gd-DOTA. (orig.).
A tick/rickettsial survey in various parts of Switzerland revealed the presence of a new, hitherto undescribed spotted fever group rickettsia ("Swiss agent") in up to 11.7% of I. ricinus collected off vegetation. Infection in ticks was found to be generalized with rickettsiae developing intracellularly and occasionally also intranuclearly. As a result of massive growth in ovarial tissues, including the germinative cells, the rate of transovarial and filial infection was 100%. The "Swiss agent" appears to be nonpathogenic for guinea pigs, domestic rabbits, and Swiss mice, but in male meadow voles (Microtus pennsylvanicus) it produces a microscopically detectable infection in the tunica vaginalis. The rickettsia grows well in tissue culture systems including chick embryo fibroblast, Vero, and vole tissue cells, when inoculated via yolk sac into 5-day-old hens' eggs, it kills 100% of the embryos after 5 to 7 days. Antigenic relatedness of the "Swiss agent" to ...
The heavy chains of Acanthamoeba myosins, IA, IB and II, turkey gizzard myosin, and rabbit skeletal muscle myosin subfragment-1 were specifically labeled by radioactive ATP, ADP, and UTP, each of which is a substrate or product of myosin ATPase activity, when irradiated with uv light at 0"0C. With UTP, as much as 0.45 mol/mol of Acanthamoeba myosin IA heavy chain and 1 mol/mol of turkey gizzard myosin heavy chain was incorporated. Evidence that the ligands were associated with the catalytic site included the observations that reaction occurred only with nucleotides that are substrates or products of the ATPase activity; that the reaction was blocked by pyrophosphate which is an inhibitor of the ATPase activity; that ATP was bound as ADP; and that label was probably restricted to a single peptide following limited subtilisin proteolysis of labeled Acanthamoeba myosin IA heavy chain and extensive cleavage with CNBr and trypsin of labeled turkey gizzard myosin heavy ...
Treatment of cultures of 3T3-L1 cells with methylisobutyl-xanthine and dexamethasone has been shown to result in accumulation of lipid and conversion to the morphology of adipocytes in more than 90% of the cells. The status of the stimulatory (Gs), inhibitory (Gi) and Go-proteins during the course of 3T3-L1 differentiation was examined. The amount of alpha subunit of Gs (#alpha#Gs), assayed by radiolabeling in the presence of cholera toxin and ["3"2P]NAD"+, increased upon differentiation as previously described by others. The amounts of #alpha#Gi and #alpha#Go assayed by radiolabeling in the presence of pertussis toxin and ["3"2P]NAD"+ increased 3-fold upon differentiation. Immunoblots of cell membranes subjected to gel electrophoresis in sodium dodecyl sulfate were probed with two rabbit antisera raised against bovine brain #alpha#Go and with one raised against the#beta#-subunit of the bovine rod-outer-segment G-protein, referred to as transducin. The ...
In 18 piglets, weighing 10-15 kg, third-degree burns or full-thickness skin excisions of 4 X 4 cm were inflicted. The effect of five dressing materials on adhesiveness to the wounds, appearance, conformability, wound contraction, bacterial count, and morphology of the wound was studied at the end of the seventh and fourteenth days without dressing changes. In 11 piglets with a burn wound, the most adherent dressing was collagen sponge(CS), followed by polyurethane sponge (PU), pigskin xenograph (PS), and xeroform. CS more effectively debrided the wound from coagulated necrotic tissue than the other dressings. Wound contraction was maximal with CS dressing (52%), followed by PU (44%), xeroform (32%), and PS (27%). In another seven piglets with full-thickness excised wounds, a velour dressing made of polytetrafluoroethylene (PTFE) or PU adhered significantly more than CS or PS. Wound contraction was greater with CS (37%) or PTFE (35%) than with PS (23%) or PU (18%). The bacterial counts ...
Two overlapping cDNA clones encoding human DNA topoisomerase II were identified by two independent methods. In one, a human cDNA library in phage {lambda} was screened by hybridization with a mixed oligonucleotide probe encoding a stretch of seven amino acids found in yeast and Drosophila DNA topoisomerase II; in the other, a different human cDNA library in a {lambda}gt11 expression vector was screened for the expression of antigenic determinants that are recognized by rabbit antibodies specific to human DNA topoisomerase II. The entire coding sequences of the human DNA topoisomerase II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is encoded by a single-copy gene. The location of the gene was mapped to chromosome 17q21-22 by in situ hybridization of a cloned fragment to ...
The overall objective of this project has been to develop immunochemical methods to quantitate unique DNA base damages in order to facilitate studies on radiation-induced damage production and repair. Specifically, we have been using antibodies raised to damaged bases to quantitate unique lesions in model systems in order to evaluate their potential biological consequences. Our approach has been to synthesize modified nucleotides or nucleosides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits or to prepare monoclonal antibodies. We have been studying damages that are stable radiolysis products found in X-irradiated DNA and thus of potential biological consequence. Our aim is to build an in vitro and in vivo data base on the interactions between model DNA lesions and such cellular enzymes as DNA polymerases and repair endonucleases. Initial studies have focused on pyrimidine ring saturation products (thymine glycol.and ...
The overall objective of this project has been to develop immunochemical methods to quantitate unique DNA base damages in order to facilitate studies on radiation-induced damage production and repair. Specifically, we have been using antibodies raised to damaged bases to quantitate unique lesions in model systems in order to evaluate their potential biological consequences. Our approach has been to synthesize modified nucleotides or nucleosides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits or to prepare monoclonal antibodies. We have been studying damages that are stable radiolysis products found in X-irradiated DNA and thus of potential biological consequence. Our aim is to build an in vitro and in vivo data base on the interactions between model DNA lesions and such cellular enzymes as DNA polymerases and repair endonucleases. Initial studies have focused on pyrimidine ring saturation products (thymine glycol.and ...
c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available
Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated....Full Text Available
Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for /sup 125/I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of /sup 125/I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of /sup 125/I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after cultures were established. Cell cycle analysis suggested that within the first 24 h and in the very late ...
The hepatic removal of albumin-bound substances from plasma requires that they dissociate from albumin. Using indirect methods, we and others have proposed that dissociation may be catalyzed by interaction...Full Text Available
We reported previously that Fas-induced hepatic failure in normal mice was attenuated or prevented by exogenous transferrin (Tf), particularly apoTf. Here we show in C57BL6J/129 mice with genetic...Full Text Available
Metabotropic glutamate receptor 2/3 (mGluR2/3) agonists were shown previously to nonselectively decrease both cocaine- and food-maintained responding in rats. mGluR2 positive allosteric modulators (PAMs)...Full Text Available
Gastrin and its carboxyl-terminal homolog cholecystokinin (CCK) exert a variety of biological actions in the brain and gastrointestinal tract that are mediated in part through one or more G protein-coupled...Full Text Available
The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the α1a and α1d adrenergic...Full Text Available
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X...Full Text Available
α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca2+-permeable homopentameric channels modulating cortical network activity and cognitive processing....Full Text Available
AimsRosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-γ (PPARγ) and -α (PPARα),...Full Text Available
Intimin facilitates intestinal colonization by enterohemorrhagic Escherichia coli O157:H7; however, the importance of intimin binding to its translocated receptor (Tir) as opposed to...Full Text Available
The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations...Full Text Available
In developing new receptor-site specific brain imaging agents labeled with I-123 for single photon emission computed tomography (SPECT), an analog of raclopride, 3-["1"2"5I]-iodo-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-hydroxy-6-me-thoxy benzamide (IBZM), was prepared using a method similar to that reported for raclopride and its derivatives. (author).
The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [125I]-DNP and used this to localize high-affinity (K(D)=0.2 nmol/L), saturable, specific binding sites in adult human heart (n=6) and coronary artery (n=8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [125I]-DNP was specific to NPR-A. Messenger RNA encoding NPR-A was identified in left ventricle and coronary artery smooth ...
We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with ...
Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural...Full Text Available
We have shown that addition of exogenous delta-aminolaevulinic acid (ALA) to rat pancreatoma AR4-2J cells in culture leads to the increased production of porphobilinogen (PBG) and the accumulation of...Full Text Available
BackgroundWe investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection...Full Text Available
LRP1 is a type-1 transmembrane receptor that mediates the endocytosis of diverse ligands. LRP1 β-chain proteolysis results in release of sLRP1 that is present in human plasma. In this study,...Full Text Available
We have isolated a human thrombomodulin cDNA, and a human genomic clone containing the putative promoter domain, as well as the translated and untranslated regions of the endothelial cell receptor....Full Text Available
G protein-coupled receptors (GPCRs) are known to modulate intracellular effectors involved in cardiac function. We recently reported homocysteine (Hcy)-induced ERK-phosphorylation was suppressed...Full Text Available
Cutaneous T-cell lymphoma is typically a clonal neoplasm of epidermotropic CD4+ T-lymphocytes that includes the entity mycosis fungoides (MF). After identification of patients with recurrent MF treated...Full Text Available
The purpose of this study was to determine if a cannabinoid CB1receptor antagonist would selectively decrease consumption of highly palatable food in non-human primates. The CB1...Full Text Available
In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic peptide analogs do not ...
We have previously shown that lymphocyte β2-adrenoceptors (AR) are under cyclical control of sex-steroid hormones with greater receptor density during the luteal phase of the menstrual...Full Text Available
We have previously described a monoclonal antibody (FA6-152), obtained by immunizing mice with fetal human erythrocytes [Edelman, Vinci, Villeval, Vainchenker, Henri, Miglierina, Rouger, Reviron, Breton-Gorius,...Full Text Available
A new proprietary de novo peptide design technique generated ten 15-residue peptides targeting and containing the leading nontransmembrane hydrophobic autocorrelation wavelengths, “modes”,...Full Text Available
Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic steatohepatitis (NASH) and associated with hypercholesterolemia, i.e. increased levels of plasma low-density...Full Text Available
Derivatives of angiotensin with a sarcosine substitution at the carboxy terminus and an aliphatic amino acid substitution at the amino terminus have been shown to be competitive ligands for the angiotensin receptor. Scatchard plots derived from saturation isotherm data in bovine adrenal particulates consistently demonstrate three to five times the number of binding sites for "1"2"5I-Sarl,Ile8-AII ("1"2"5I-SI-AII) than for "1"2"5I-AII in experiments in which the two ligands are run side-by-side. A significant difference between "1"2"5I-AII and "1"2"5I-SI-AII binding to detergent solubilized angiotensin receptors was observed. Of the "1"2"5I-AII binding sites, about 85-90% were recovered upon solubilization. In contrast, the recovery of "1"2"5I-SI-AII binding sites was only 4-5%. To determine whether binding sites labeled in the soluble state represent biologically significant AII receptors, they examined the ability of ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; ...
1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocytic 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells...Full Text Available
BackgroundThe ability of catecholamines to stimulate bacterial growth was first demonstrated just over a decade ago. Little is still known however, concerning the nature of the putative...Full Text Available
Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available
beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B chain was able to induce cytotoxic effects on SK-N-SH cells as beta-Bgt did. Abolishment of PLA(2) activity did not significantly ...
In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 ± 9.2 pmol nitric...Full Text Available
This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.
This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.
Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available
In superior cervical ganglion (SCG) neurons calcium-induced calcium release (CICR), mediated by ryanodine receptors (RyRs), contributes to stimulation-evoked intracellular calcium ([Ca2+]i)...Full Text Available
The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown....Full Text Available
Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available