Travel Assistance in China 1993-1995.
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Journal Article↗
Biomedical subjects
Y Song
Publications and source records attributed to Y Song.
A modified method for examining the cardiac conduction system.
A revised technique is described in which the sino-atrial node, the atrio-ventricular node and the distal part of the His bundle and the bundle brances of the cardiac conduction system are demonstrated in longitudinal sections through cutting of 4-5 blocks. The longitudinal sectioning allows observation of continuity between different components of the cardiac conduction tissue. This method reduces the workload and hopefully encourages the pathologist to make the examination of the cardiac conduction system a part of the routine procedure.
Atrioventricular Node↗
Binding of thrombin to the G-protein-linked receptor, and not to glycoprotein Ib, precedes thrombin-mediated platelet activation.
The roles of the G-protein-linked thrombin receptor and platelet glycoprotein Ib (GPIb) as alpha-thrombin-binding sites on platelets remain controversial. alpha-Thrombin has been proposed to bind to both GPIb and the hirudin-like domain of the G-protein-linked receptor (from which it cleaves the NH2-terminal extracellular domain to release a 41-mer peptide (TR-(1-41), where TR is alpha-thrombin receptor)) to initiate platelet activation. Using affinity-purified rabbit anti-human TR-(1-41) IgG and immunoblotting, we demonstrated TR-(1-41) release from platelets suspended in Tyrode's buffer containing 2 mM CaCl2 and incubated with >/=0.5 nM alpha-thrombin for 10-60 s at 37 degrees C. As quantified by enzyme-linked immunosorbent assay, 0.32-0.59 nM TR-(1-41) was released from washed platelets (5 x 10(11) platelets/liter) after their incubation with 10 nM alpha-thrombin for 10 s. Parallel binding of alpha-thrombin to and activation of the platelets were confirmed by flow cytometry. A monoclonal antibody against the hirudin-like domain of the G-protein-linked receptor abrogated alpha-thrombin binding to platelets, cleavage of TR-(1-41), and platelet activation by </=1.0 nM (but not 10 nM) alpha-thrombin. Proteolysis of platelet GPIb with Serratia marcescens protease or O-sialoglycoprotein endopeptidase had no effect on alpha-thrombin binding to platelets or their subsequent activation. In contrast, chymotrypsin, which cleaves both GPIb and the G-protein-linked receptor, abrogated alpha-thrombin binding to platelets, TR-(1-41) release, and platelet activation. Furthermore, monoclonal antibodies directed against the reported alpha-thrombin-binding site on GPIb inhibited neither alpha-thrombin binding to nor activation of the platelets. Thus, alpha-thrombin binds to and cleaves the G-protein-linked receptor when it activates platelets, and GPIb does not appear to serve as an important binding site when alpha-thrombin activates platelets.
Antibodies, Monoclonal↗
2,6-di-tert-butylphenols: a new class of potent and selective PGHS-2 inhibitor.
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Cyclooxygenase Inhibitors↗
Inflammation of small airways in asthma.
This study was designed to examine the inflammatory process in the central and peripheral airways of surgically resected lungs from asthmatic and nonasthmatic subjects. Lung specimens were inflated with cryoprotective, rapidly frozen, and systematically sampled. Cryosections prepared from frozen tissue blocks were fixed in acetone/methanol and immunostained with monoclonal antibodies by using the alkaline phosphatase-anti-alkaline phosphatase technique to detect CD3 (T cells), major basic protein (total eosinophils), EG2 (activated eosinophils), anti-tryptase (mast cells), anti-elastase (neutrophils), and CD68 (macrophages). All airways from patients with asthma demonstrated a significant increase in the numbers of T cells and total and activated eosinophils compared with airways from nonasthmatic subjects (p < 0.001). In the patients with asthma, the numbers of activated eosinophils but not T cells were significantly greater in airways with an internal perimeter less than 2 mm compared with those with an internal perimeter greater than 2 mm (p < 0.05). There were also significantly higher numbers of major basic protein-positive eosinophils, when expressed as a fraction of the alveolar wall tissue, in patients with asthma compared with control subjects (p < 0.05). In asthmatic airways with an internal perimeter of more than 2 mm, there was a greater number of activated eosinophils in the tissue between the epithelium and the smooth muscle compared with the tissue between the smooth muscle layer and lung parenchyma (p < 0.05). In contrast, there was a greater number of total eosinophils in the outer airway layer compared with the inner airway layer (p < 0.05). These results show that there is a similar but more severe inflammatory process present in the peripheral compared with the central airways of patients with asthma, which is consistent with the fact that the smaller airways are a major site of obstruction in asthma.
Adult↗
The use of SCID mice for the growth of retinoblastoma cell lines and for the establishment of xenografts from primary tumours.
We investigated the possibility of growing primary retinoblastoma tumour tissue in SCID mice. In preliminary experiments with the WERI retinoblastoma cell line injected subcutaneously in SCID mice, tumours arose at only 25% of the inoculation sites. After mixing these cells with a reconstituted basement membrane extracellular matrix (Matrigel) prior to inoculation, tumours arose at 100% of inoculated sites. When primary retinoblastoma cells were injected subcutaneously into SCID mice in the presence of Matrigel, tumours arose in 5/8 cases. On average, the latency period was 4 months before the tumours were palpable. Histopathological examination of the tumours showed that they resembled surgically resected human retinoblastomas and one of the tumours formed pseudo-rosettes which is a characteristic of these tumours. Unfortunately, when these xenografted tumours were introduced into tissue culture, it was not possible to establish cell lines directly and the cultures were soon overgrown by mouse cells which could clearly be shown to be infiltrating the tumour. The ability to grow retinoblastoma cell lines and primary tissue subcutaneously in SCID mice offers a convenient model system to study the genetics of tumorigenesis in this tumour type and possibly an opportunity to study the role of chemotherapy in the treatment and progression of the disease.
Animals↗
A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: the 2,2'-dithiobisbenzamides.
As part of the National Cancer Institute's Drug Screening Program, a new class of antiretrovirals active against the human immunodeficiency virus HIV-1 has been identified, and the HIV-1 nucleocapsid protein NCp7 was proposed as the target of antiviral action. The 2,2'-dithiobis-[4'-(sulfamoyl)benzanilide] (3x) and the 2,2'-dithiobis(5-acetylamino)benzamide (10) represented the prototypic lead structures. A wide variety of 2,2'-dithiobisbenzamides were prepared and tested for anti-HIV-1 activity, cytotoxicity, and their ability to extrude zinc from the zinc fingers for NCp7. The structure-activity relationships demonstrated that the ability to extrude zinc from NCp7 resided in the 2,2'-dithiobisbenzamide core structure. The 3,3' and the 4,4' isomers were inactive. While many analogs based upon the core structure retained the zinc extrusion activity, the best overall anti-HIV-1 activity was only found in a narrow set of derivatives possessing carboxylic acid, carboxamide, or phenylsulfonamide functional groups. These functional groups were more important for reducing cytotoxicity than improving antiviral potency or activity vs NCp7. All of the compounds with antiviral activity also extruded zinc from NCp7. From this study several classes of low microM anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS.
Anti-HIV Agents↗
Behavioral analysis of drinking behaviors in polydipsic patients with chronic schizophrenia.
The authors describe drinking and voiding behaviors that differentiate between psychiatric patients with polydipsia and patient controls. Observations of 9 polydipsic patients and 6 controls were conducted for 153 hr and had high interrater reliability. Polydipsic patients drank 3 times as frequently, ingesting 5 times as much fluid as the controls. They voided 4 times as often, eliminated 5 times as much urine, and evidenced greater diurnal weight shifts. A higher bout frequency and a shorter time interval between drinks differentiated polydipsic patients from controls, whereas amount drunk per bout and rate of drinking were similar across groups. The authors' findings have implications for improving detection of polydipsia, understanding its neurobiology, and developing more efficacious behavioral interventions.
Adult↗
Mechanism of gastric acid hypersecretion in patients with islet cell tumor without hypergastrinemia: studies in rats.
BACKGROUND & AIMS: A nongastrin acid-stimulating peptide (NGASP) has been found in ulcerogenic pancreatic tumor syndrome without hypergastrinemia. The mechanism of gastric acid hypersecretion by NGASP was investigated in rats. METHODS: In vivo, gastric acid secretion and in vitro histamine release from enterochromaffin-like (ECL) cells in responses to tumor extract (TE) and synthetic human gastrin-17 I or pentagastrin (PG) were studied. Whether the 2 secretagogues potentiate each other was determined. RESULTS: TE dose-dependently stimulated histamine release, which was not blocked by a cholecystokinin (CCK)-B receptor antagonist. When TE was incubated with trypsin, the activity was abolished but was not affected by antibody. However, when rats were pretreated with antigastrin serum or CCK-B receptor antagonist, the acid secretion by TE was virtually abolished. The dose response of acid secretion to TE in the rats receiving PG in a threshold dose was significantly greater than that achieved by TE alone. Similarly, the dose response to PG combined with a threshold dose of TE was significantly greater than that produced by PG alone. CONCLUSIONS: NGASP stimulates histamine release from ECL cells, but the release is not mediated via CCK-B/gastrin receptor. NGASP and gastrin may potentiate each other to produce acid hypersecretion in ulcerogenic pancreatic tumor syndrome.
Adenoma, Islet Cell↗
Studies of the renal action of melatonin: evidence that the effects are mediated by 37 kDa receptors of the Mel1a subtype localized primarily to the basolateral membrane of the proximal tubule.
The pineal hormone melatonin controls circadian behavior of a variety of organs in different species, including humans. However, the precise mechanism (or mechanisms) by which this occurs remains largely unknown. At the cellular level its effects are believed to be mediated via interaction with specific melatonin receptors (MR), which have previously been cloned from human brain (Mel1a) and retina (Mel1b). At the tissue level, MR have been investigated primarily through empirical definition of specific binding sites, but so far there has been little success in biochemical or molecular characterization of native MR. In the kidney, there is strong circumstantial evidence that melatonin affects diurnal variations in renal function, but relatively little is known about the overall glomerular vs. tubular contributions to these effects. The strategy behind the present study was to use a panel of peptide-specific antibodies to identify MR proteins in various tissues, and from a determination of the intrarenal distribution of MR, gain insight into the mechanism by which melatonin might regulate kidney function. We used two peptide-specific antibodies directed against different regions of Mel1a to identify MR. Our results show that the native Mel1a receptor is a 37 kilodalton (kDa) protein in human and rat brain. Further, immunofluorescent studies carried out in guinea pig kidney have revealed that anti-Mel1a antibody is also localized to the basolateral membrane (BLM) of the renal cortical epithelium, especially the early proximal tubule. Immunoblotting of purified BLM fractions from guinea pig renal cortex and small intestine using the two different peptide-specific antibodies reveals the presence of a single peptide-blockable band at 37 kDa. These same BLM fractions also demonstrate the presence of high-affinity 2-[125I]iodomelatonin (125I-MEL) binding sites, with the pharmacological specificity of binding expected of the Mel1a receptor subtype, inhibited by guanosine 5'-O-(3'-thiotriphosphate) (GTPgammaS) and pertussis toxin. We conclude that functional MR in guinea pig kidney and small intestine are of the Mel1a subtype, and are expressed as 37 kDa proteins localized to the BLM and coupled to a pertussis toxin-sensitive G-protein (Gi). This localization strongly suggests that the proximal tubule plays a significant role in mediating the renal action of melatonin.
Animals↗
Loosening and osteolysis of cemented joint arthroplasties. A biologic spectrum.
The purpose of this study was to characterize the cell types (using immunohistochemistry) and cytokine expression (using in situ hybridization) of tissues surrounding well fixed and loose cemented prostheses undergoing revision. Clinical and radiographic data were gathered prospectively for a series of cemented total joint replacements undergoing revision. Three groups were identified: (1) loose implants with osteolysis (10 specimens), (2) loose implants without osteolysis (11 specimens), and (3) well fixed implants (7 specimens). At surgery, a specimen was harvested from the bone cement interface. Immunohistochemical staining was performed using monoclonal antibodies to identify macrophages and lymphocyte subgroups. Human antisense probes were selected to identify the mRNA for specific cytokines using in situ hybridization. The percentage of positively staining cells was determined for each antibody or probe using a grid counting technique. Tissues from loose cemented prostheses with osteolysis contained significantly greater numbers of macrophages and T lymphocytes compared with tissues from loose and well fixed cemented prostheses without osteolysis. The number of interleukin-1 and interleukin-6 positive cells was highest in specimens with osteolysis and lowest in specimens from well fixed prostheses. These cytokines modulate the growth and differentiation of cells in the immune system and the monocyte and macrophage system and mediate the remodeling of bone and mesenchymal tissues. Specific cell populations and cytokine profiles appear to be involved in periprosthetic osteolysis; this information may be useful in planning strategies for prevention and treatment.
Aged↗
Differential inhibitory effects of melatonin analogs and three naphthalenic ligands on 2-[125I]iodomelatonin binding to chicken tissues.
We have compared the 50% inhibition values of 2-[125I]iodomelatonin ([125I]Mel) competition curves by melatonin and 3 naphthalenic ligands, N-[2-(7-methoxy-1-naphthyl) ethyl] cyclobutane carboxamide (S20642), N-propyl N-[2-(7-methoxy-1-naphtyl) ethyl] urea (S20753), and N-[2-(7-methoxy-1-naphthyl) ethyl] crotonamide (S20750), using membrane preparations of four tissues (lung, spleen, brain, and kidney) of the chicken simultaneously. In retired breeders, we have demonstrated that the affinities of S20642 were similar in the lung and spleen. However they were 2-fold lower in the brain and 80-fold lower in the kidney. Similar differential binding affinities to the melatonin receptors were observed in the four tissues of young male chicks. This suggests that age and sex have little influence on the differential inhibitory properties of melatonin and S20642 in the tissues studied. The addition of guanosine 5'-O-thiotriphosphate (GTPgammaS), which encouraged the uncoupling of melatonin receptor to the G protein complex, lowered the binding affinity of melatonin and S20642 in the tissues studied but their differential affinities in the four tissues were however maintained. The affinities of 5-methoxy-N-cyclopropanoyltryptamine (CPMT) in the kidney were also 5-10-fold lower than those in the lung, spleen, and brain of young male chicks. The distinctive differential affinities of melatonin, S20642, and CPMT for [125I]Mel binding sites in the chicken lung, spleen, brain, and kidney indicated that the binding sites in these tissues are heterogeneous. Our study implicated that the naphthalenic ligand S20642 may be a useful melatonin analog to distinguish melatonin receptor subtypes in tissues and a possible drug candidate worthwhile for further investigations.
Aging↗
The human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein zinc ejection activity of disulfide benzamides and benzisothiazolones: correlation with anti-HIV and virucidal activities.
It has been shown previously by our group and others that a series of four disulfide benzamides with cellular anti-human immunodeficiency virus (HIV) activity can eject zinc from HIV type 1 nucleocapsid protein (NCp7) in vitro while analogs without antiviral activity do not. We also found that the zinc ejection activity correlates with the loss of the ability of NCp7 to bind to HIV psi RNA in vitro. These observations indicate that the antiviral disulfide benzamides may act at a novel retroviral target of action, i.e., the nucleocapsid protein. The present studies examine the relationship among disulfide benzamide structure, in vitro NCp7 zinc ejection activity, and antiviral activity for a larger series of compounds. All of the antiviral disulfide benzamides were found to eject NCp7 zinc, while some disulfide benzamides with zinc ejection activity are not antiviral. Utilizing the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid), it was determined that the o-amido-phenyl disulfides being studied cyclize in aqueous solution to form benzisothiazolones. A series of benzisothiazolones, which are stable in solution in the absence of dithiothreitol, were found to eject NCp7 zinc at a rate similar to that of their disulfide benzamide analogs and to possess similar antiviral activity. It was also found that the relative rates of HIV inactivation by various disulfide benzamides and benzisothiazolones correlate with their relative kinetic rates of NCp7 zinc ejection, which is consistent with the nucleocapsid protein being the target of action of these compounds.
Anti-HIV Agents↗
Expression of adenine nucleotide translocator parallels maturation of respiratory control in heart in vivo.
Changes in the relationship between myocardial high-energy phosphates and oxygen consumption in vivo occur during development, implying that the mode of respiratory control undergoes maturation. We hypothesized that these maturational changes in sheep heart are paralleled by alterations in the adenine nucleotide translocator (ANT), which are in turn related to changes in the expression of this gene. Increases in myocardial oxygen consumption (MVO2) were induced by epinephrine infusion in newborn (0-32 h, n = 6) and mature sheep (30-32 days, n = 6), and high-energy phosphates were monitored with 31P nuclear magnetic resonance. Western blot analyses for the ANT1 and the beta-subunit of F1-adenosinetriphosphatase (ATPase) were performed in these hearts and additional (n = 9 total per group) as well as in fetal hearts (130-132 days of gestation, n = 5). Northern blot analyses were performed to assess for changes in steady-state RNA transcripts for these two genes. Kinetic analyses for the 31P spectra data revealed that the ADP-MVO2 relationship for the newborns conformed to a Michaelis-Menten model but that the mature data did not conform to first- or second-order kinetic control of respiration through ANT. Maturation from fetal to mature was accompanied by a 2.5-fold increase in ANT protein (by Western blot), with no detectable change in beta-F1-ATPase. Northern blot data show that steady-state mRNA levels for ANT and beta-F1-ATPase increased approximately 2.5-fold from fetal to mature. These data indicate that 1) respiratory control pattern in the newborn is consistent with a kinetic type regulation through ANT, 2) maturational decreases in control through ANT are paralleled by specific increases in ANT content, and 3) regulation of these changes in ANT may be related to increases in steady-state transcript levels for its gene.
Aging↗
Studies of melatonin effects on epithelia using the human embryonic kidney-293 (HEK-293) cell line.
The expression of melatonin receptors (MR) of the Mel1a subtype in basolateral membrane of guinea pig kidney proximal tubule suggests that melatonin plays a role in regulating epithelial functions. To investigate the cellular basis of melatonin action on epithelia, we sought to establish an appropriate in vitro culture model. Epithelial cell lines originating from kidneys of dog (MDCK), pig (LLC-PK1), opossum (OK), and human embryo (HEK-293) were each tested for the presence of MR using 2-[125I]iodomelatonin (125I-MEL) as a radioligand. The HEK-293 cell line exhibited the highest specific 125I-MEL binding. By intermediate filament characterization, the HEK-293 cells were determined to be of epithelial origin. Binding of 125I-MEL in HEK-293 cells demonstrated saturability, reversibility, and high specificity with an equilibrium dissociation constant (Kd) value of 23.8 +/- 0.5 pM and a maximum number of binding sites (Bmax) value of 1.17 +/- 0.11 fmol/mg protein (n = 5), which are comparable with the reported Kd and Bmax values in human kidney cortex. Coincubation with GTPgammaS (10 microM) and pertussis toxin (100 ng/ml) provoked a marked decrease in binding affinity (Kd was increased by a factor of 1.5-2.0), with no significant difference in Bmax. Melatonin (1 microM) decreased the forskolin (10 microM) stimulated cAMP level by 50%. HEK-293 cells do not express dopamine D1A receptor. Following transient transfection of HEK-293 cells with human dopamine D1A receptor (hD1A-R), exposure of the cells to dopamine stimulated an increase in the level of cAMP. Similarly, transient transfection of HEK-293 cells with rat glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and PTH type 1 receptors, each resulted in an hormone inducible increase in cAMP levels. Surprisingly, only the stimulatory effect of dopamine could be inhibited by exposure to melatonin. The inhibitory effect of melatonin on dopamine D1-induced increase in cAMP was completely inhibited by pertussis toxin (100 ng/ml, 18 h). Immunoblot and immunocytochemical studies were carried out using two polyclonal antibodies raised against the extra and cytoplasmic domains of Mel1a receptor. Immunoblot studies using antibody against the cytoplasmic domain of Mel1a receptor confirmed the presence of a peptide blockable 37 kDa band in HEK-293 cells. Indirect immunofluorescent studies with both antibodies revealed staining predominantly at the cell surface, but staining with the antibody directed against the cytoplasmic domain required prior cell permeabilization. By RT-PCR, HEK-293 cells express both Mel1a and Mel1b messenger RNAs, but the messenger RNA level for Mel1b is several orders of magnitude lower than for Mel1a. We conclude that HEK-293 cells express MR predominantly of the Mel1a subtype. Our evidence suggests that one of the ways that melatonin exerts its biological function is through modulation of cellular dopaminergic responses.
Animals↗
Isolation of genomic DNA from claw clippings for genetic analysis in chickens.
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Animals↗
[Cardiopulmonary effects of two modes of mechanical ventilation in dogs with and without acute lung injury-comparison of pressure regulated biphasic airway presure ventilation and intermittent positive pressure ventilation].
OBJECTIVE: To compare the cardiopulmonary effect of pressure regulated biphasic airway pressure (BiPAP) and intermittent positive pressure ventilation (IPPV). METHOD: Airway pressure, hemodynamics and blood gases were measured during the two ventilatory modalities with 0, 0.5, 1 kPa external end-expiratory pressure (EEP) in dogs with and without oleic acid-induced lung injury. RESULTS: No matter whether there is lung injury, airway pressure during BiPAP is lower compared with IPPV, but there is no difference in cardiac output. In dogs with lung injury, PaO2 during BiPAP is higher than that during IPPV. CONCLUSIONS: Compared with IPPV, BiPAP effected a decrease in airway pressure, and PaO2 was improved in dogs with lung injury, although the cardiac output was not increased.
Animals↗
[Effect of dietary fiber on antioxidation in rats].
The antioxidative effect of cellulose, wheat bran and pectin was studied in rats. Wistar rats (40) were randomly divided into 4 groups, 3 groups were fed with the fibers at a level of 10% in weight, the 4th group consumed stock food as control. After 3 months' feeding, MDA in serum and in RBC membrane of the 3 treated groups were significantly lower than that of the control group. The RBC membrane fluidity was significantly increased. It is suggested that these three kinds of dietary fibers can reduce the level of lipid peroxidation and inhabit free radical injury to RBC membrane in rats.
Animals↗