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Biomedical subjects

Y F Wang

Publications and source records attributed to Y F Wang.

At least 109 records · Page 6Linked to original sources
PubMed1997

Phase I study of the antineovascularization drug CM101.

CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produce evidence for severe, and possibly tumor-specific, inflammation. Further study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.

Adult↗
PubMed1996

The effect of systemic and central nitric oxide administration on milk availability in lactating rats.

This study examined the effect of nitric oxide (NO) on milk transfer in rats. Pups nursed by mothers that received chronic systemic injections of sodium nitroprusside (SNP) weighed significantly less than pups of mothers treated with either saline or N omega-nitro-L-arginine (NNLA). Intracerebroventricular injection of SNP or L-arginine (L-arg) but not NNLA or saline, caused a significant reduction of milk transfer from mother to pups after a 12 h separation period. Systemic oxytocin (OT) injection reversed the effect of central injection of SNP. Furthermore, SNP and L-arg inhibited, whereas NNLA permitted the characteristic milk ejection burst of OT neurones without changing myoepithelial tissue response to systemic OT. These observations suggest that NO may be involved in the regulation of milk ejection bursts and milk transfer.

Animals↗
PubMed1996

Multiple stat complexes interact at the interferon regulatory factor-1 interferon-gamma activation sequence in prolactin-stimulated Nb2 T cells.

Interferon regulatory factor-1 (IRF-1) is a major immediate early gene induced by prolactin (PRL) in a biphasic, cell cycle-dependent manner in Nb2 T cells. This biphasic expression (30 min and 10 h) is mediated in part by an interferon-gamma activation sequence (GAS) in the IRF-1 promoter which binds factors belonging to the Signal Transducers and Activators of Transcription (Stat) family. By electrophoretic mobility shift assays (EMSA), Stat1 alpha was found to be the major and Stat5a a minor component of the 30 min complex. At 10 h, Stat-like factors were again found at the IRF-1 GAS. Western blot analyses show that Stat5a was rapidly induced by PRL to enter the nucleus, but unexpectedly, Stat1 alpha and the alternatively-spliced Stat1 beta were already present in the uninduced nucleus. Further, Stat1 alpha but not Stat1 beta is preferentially tyrosine phosphorylated in response to PRL stimulation. Our studies suggest that multiple Stat complexes may contribute to the biphasic transcription of the IRF-1 gene in PRL-stimulated T cells.

DNA-Binding Proteins↗
PubMed1996

Amplitudes and time courses of milk ejection bursts of oxytocin neurons in the midbrain-hemitransected lactating rat.

In the midbrain-hemitransected rats, 22 pairs of oxytocin neurons were recorded from 17 rats. Of the bursts on the lesioned side, the amplitude was smaller, the onset time was later and the burst span was shorter (P < 0.01). These results indicated that the amplitude and time course of the burst of oxytocin neurons mainly depend on suckling information from the nipples on their opposite side.

Animals↗
PubMed1996

Crystal structures of various maltooligosaccharides bound to maltoporin reveal a specific sugar translocation pathway.

BACKGROUND: Maltoporin (which is encoded by the lamB gene) facilitates the translocation of maltodextrins across the outer membrane of E. coli. In particular, it is indispensable for the transport of long maltooligosaccharides, as these do not pass through non-specific porins. An understanding of this intriguing capability requires elucidation of the structural basis. RESULTS: The crystal structures of maltoporin in complex with maltose, maltotriose and maltohexaose reveal an extended binding site within the maltoporin channel. The maltooligosaccharides are in apolar van der Waals contact with the 'greasy slide', a hydrophobic path that is composed of aromatic residues and located at the channel lining. At the constriction of the channel the sugars are tightly surrounded by protein side chains and form an extensive hydrogen-bonding network with ionizable amino-acid residues. CONCLUSION: Hydrophobic interactions with the greasy slide guide the sugar into and through the channel constriction. The glucosyl-binding subsites at the channel constriction confer stereospecificity to the channel along with the ability to scavenge substrate at low concentrations.

Bacterial Outer Membrane Proteins↗
PubMed1996

Identification of the major site of rat prolactin phosphorylation as serine 177.

Phosphorylation of prolactin by endogenous protein kinases within isolated secretory granules was shown to result in the production of both phosphoserine and phosphothreonine residues. The majority of the radiolabel was determined to be present in the C terminus of the molecule after specific cleavage with glandular kallikrein. Glandular kallikrein cleaves in three places at the C terminus, liberating three small peptides, only one of which contains a phosphorylatable residue. Sequencing of this phosphopeptide showed it to be Arg175-Lys185. Thus the major site of prolactin phosphorylation was determined to be serine 177. Using a synthetic peptide equivalent to this region of the molecule (Ser161-Val180), serine 177 was demonstrated to be a substrate for protein kinase A as well as for one of the endogenous granule kinases. Inclusion of the synthetic peptide in an endogenous granule phosphorylation reaction resulted in competition for the kinase and reduced phosphorylation of prolactin. Protein kinase A phosphorylation of purified prolactin resulted in the production of only phosphoserine and primarily the most abundant (monophosphorylated) variant. We conclude that serine 177 is the major in vivo phosphorylation site of rat prolactin and that phosphorylation of this site can be reproduced by protein kinase A in vitro. The minor threonine phosphorylation site was demonstrated by two-dimensional tryptic peptide mapping and mass analysis to be either threonine 58 or 63, both of which are contained within a single peptide.

Amino Acid Sequence↗
PubMed1996

Intercellular adhesion molecule-1-deficient mice are less susceptible to cerebral ischemia-reperfusion injury.

Neutrophil emigration is mediated by adhesion proteins that are highly expressed on the endothelial surface during inflammatory processes in the brain. Intercellular adhesion molecule-1 (ICAM-1) is an inducible adhesion molecule that binds to leukocyte integrins and facilitates neutrophil adhesion and transendothelial migration. To study the role of ICAM-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in ICAM-1-deficient mice generated by gene targeting in embryonic stem cells. Transient focal ischemia was induced by occluding the left middle cerebral artery for 3 hours followed by a 21- or 45-hour reperfusion period. When compared with their wild-type littermates, ICAM-1-deficient mice were less susceptible to cerebral injury as demonstrated by a 5.6- or 7.8-fold reduction in infarction volume, respectively. These data support the premise that neutrophil adhesion in ischemic areas may be deleterious and that ICAM-1 deficiency reduces neurological damage after transient focal cerebral ischemia.

Animals↗
PubMed1996

Synthesis and blood compatibility evaluation of segmented polyurethanes based on cholesterol and phosphatidylcholine analogous moieties.

New segmented polyurethanes based on cholesterol and phosphatidylcholine analogous moieties were synthesized. The soft segments used in this study were the poly(butadiene), poly(isoprene) or hydrogenated poly(isoprene) glycols; the hard segments of these segmented polyurethanes were composed of 4,4'-methylenediphenyl diisocyanate, 2-[bis(2-hydroxyethyl)methylammonio]ethyl 5-cholesten-3 beta-yl phosphate and 1,4-butanediol. The blood compatibilities of synthesized segmented polyurethanes were evaluated by platelet-rich plasma contact studies and scanning electron microscopy observation using glass as the reference. The results show that the blood compatibilities of the synthesized segmented polyurethanes have great difference between the glass contact side and air exposed side for the same cast films. Generally, the hydrogenated poly(isoprene)-based segmented polyurethane is the best surface in terms of platelet adhesion, and the morphology of adhered platelets undergoes the lowest degree of variation among the segmented polyurethanes investigated in this study.

Biocompatible Materials↗
PubMed1996

Characterization of neurokinin type 1 receptor in canine small intestinal muscle.

The binding of [3H]substance P (SP) was localized and characterized in canine small intestine. The highest density of [3H]SP binding occurred in the fraction enriched in circular muscle membranes (Bmax 148 +/- 14 fmol/mg; Kd 0.81 +/- 0.01 nM). In the kinetics studies binding was reversible, yielding a similar Kd value. NK1 agonists and antagonists fully displaced, but ligands at the NK2 and NK3 receptor only partially displaced, [3H]SP binding. The potency order of displacement resembled that for the human NK1 receptor ortholog rather than the rat NK1 receptor. Densities of [3H]SP binding were lower in myenteric plexus and longitudinal muscle membrane fractions, but suggested binding in both neural and muscle membranes. The conclusion is that NK1 receptors occur primarily in canine intestine circular muscle plasma membrane.

5'-Nucleotidase↗
PubMed1996

Milk ejection bursts of supraoptic oxytocin neurones during bilateral and unilateral suckling in the rat.

Extracellular recordings of the electrical activity of oxytocin neurones were made from the supraoptic nuclei (SON) of lactating rats, and the milk-ejection bursts and the background activity of oxytocin neurones were investigated during unilateral and bilateral suckling. When application of pups was limited to the nipples on either the same side (ipsilateral suckling) or the side opposite (contralateral suckling) to the oxytocin neurone recorded, the burst amplitude and background firing rate were significantly (P < 0.05) lower and the inter-burst interval was significantly (P < 0.05) longer than during bilateral suckling. Furthermore, the burst amplitude was significantly (P < 0.05) lower during ipsilateral suckling than during contralateral suckling. The majority of the oxytocin neurones showed a gradual increase in the burst amplitude during bilateral (88.9%) and contralateral (77.3%) suckling, but during ipsilateral suckling only 40% of the neurones did. The inter-burst interval became shorter with the progress of the milk ejection reflex during any mode of suckling. Three pairs of oxytocin neurones recorded simultaneously from both SON were successfully tested for the effect of bilateral and unilateral suckling on the electrical activity, and the results showed the same direction of change in the burst amplitude, background activity and burst interval as shown in single side recordings. These findings indicate that the burst amplitude mainly depends on the amount of afferent suckling signals arising from the nipples on the side opposite to the recording side, and that there may exist bilateral summation centres coordinating with the synchronization mechanism of milk-ejection bursts of oxytocin neurones.

Animals↗
PubMed1996

Immune response to epitopes of hepatitis C virus (HCV) structural proteins in HCV-infected humans and chimpanzees.

Hepatitis C virus (HCV)-infected humans and chimpanzees were studied for reactivity with linear epitopes in HCV H strain structural proteins. In 10 HCV-infected patients, epitopes were mostly mapped to the capsid and E1 proteins but not to E2. However, serum from 1 HCV-infected blood donor with a high anti-capsid titer reacted with multiple epitopes including E2. By contrast, antibody to capsid epitopes was seen in sera from HCV-rechallenged chimpanzees but not from chronically infected animals. No reactivity was observed to GOR epitope in chimpanzees, while 6 of 11 human subjects reacted with this host-coded antigen. Reactivity to rare epitopes in E2 was seen in chimpanzees with chronic and self-limited infections. Reactivity to one peptide of E1 (aa 316-329) was observed in 10 of 11 sera from HCV-infected humans and 11 of 15 chimpanzee sera. However, reactivity to this epitope was also seen in normal chimpanzees and in 6 (7.1%) of 84 uninfected human subjects.

Amino Acid Sequence↗
PubMed1996

Complete recovery after normothermic hemorrhagic shock and profound hypothermic circulatory arrest of 60 minutes in dogs.

OBJECTIVE: We hypothesize that during severe normothermic hemorrhagic shock (HS), induction of profound hypothermic circulatory arrest (PHCA) of 60 minutes to allow repair of otherwise lethal injuries in a bloodless field, can be survived without brain damage. In previous dog studies, normothermic HS with mean arterial pressure (MAP) of 40 mm Hg for 30 minutes, followed by PHCA of 2 hours at brain (tympanic membrane) temperature of 5 to 10 degrees C and core temperature of 10 degrees C, induced and reversed with cardiopulmonary bypass, resulted in survival with mild histopathologic brain damage. This study was designed to determine the severity of HS that can safely allow 1 hour of PHCA. In pilot studies with HS at MAP 30 mm Hg for 90 minutes with or without subsequent PHCA of 60 minutes there were no survivors. METHODS: In the definitive study, outcomes in four groups of five dogs each were compared: group I, HS at MAP 30 mm Hg for 60 minutes and normothermic fluid resuscitation; group II, HS at MAP 30 mm Hg for 60 minutes, PHCA for 60 minutes, and resuscitation; group III, HS at MAP 40 mm Hg for 60 minutes and normothermic fluid resuscitation; and group IV, HS at MAP 40 mm Hg for 60 minutes, PHCA for 60 minutes, and resuscitation. Controlled ventilation was maintained for at least 20 hours and intensive care for 72 hours. RESULTS: In groups I and II, two of five dogs in each group survived to 72 hours. In groups III and IV, all ten dogs survived. All survivors were functionally normal, with neurologic deficit scores (0% = normal, 100% = brain dead) of < 10%. Light microscopic scoring of 18 brain regions revealed no ischemic changes. All nonsurvivors had a severe metabolic acidemia after HS and developed multiple organ failure, including pulmonary edema, pneumonia, and intestinal necrosis. CONCLUSIONS: The critical level of hypotension during 60 minutes normothermic HS that is compatible with survival in dogs is a MAP of between 30 and 40 mm Hg. After otherwise survivable severe normothermic HS of 60 minutes, PHCA of 60 minutes does not add brain damage or mortality, and may allow survival from injuries that would otherwise be irreparable.

Animals↗
PubMed1996

Peptide YY receptor in submucosal and myenteric plexus synaptosomes of canine small intestine.

PYY receptors were characterized and their loci determined in canine small intestine. The density of 125I-labeled peptide tyrosine tyrosine (PYY) binding was highest in myenteric (MY) and submucosal (SUB) plexus fractions enriched in synaptosomes. Two binding sites [high affinity (H) and low affinity (L)] were found in the submucosal synaptosome-enriched membrane: dissociation constant (Kd)H = 7.6 pM, maximal binding capacity (Bmax)H = 28 fmol/mg; KdL = 0.18 nM, BmaxL = 120 fmol/mg protein. The binding of 125I-PYY reached a maximum within 30 min; dissociation was incomplete in the presence of unlabeled PYY. The rate of dissociation was enhanced after exposure of synaptosomes to guanosine 5'-O-(3-thiotriphosphate). Binding of 125I-PYY was completely inhibited by neuropeptide Y (NPY)-(13-36) (in SUB and MY) and by [Leu31,Pro34]NPY (in MY) but only partially by [Leu31,Pro34]NPY in SUB, suggesting the presence of Y2 receptor in SUB and the presence of Y1 and Y2 receptors in MY. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the PYY receptor complex revealed a radioactive band at 70 kDa. The PYY receptors in the canine small intestinal myenteric and submucosal plexus correspond in location to that of PYY in synaptosomes and are coupled with G proteins. Different subtypes are present in different loci.

Animals↗
PubMed1996

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) soft segment.

A new haemocompatible phospholipid polyurethane based on hydrogenated poly(isoprene) glycol (HPIP) and 4,4'-methylendiphenyl diisocyanate (MDI) was synthesized using 2-[bis(2-hydroxyethyl)methyl-ammonio]ethylstearylphosphate (BESP) and 1,4-butanediol (BD) as chain extender. The bulk and surface characteristics of this material was investigated by differential scanning calorimetry (DSC), dynamic viscoelasticity and tensile property measurements, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurement. This polymer possessed a hydrophobic surface revealed by contact angle measurement. The haemocompatibility of this polyurethane was evaluated by platelet rich plasma (PRP) contacting studies and scanning electron microscopy (SEM) observation using medical grade poly(vinyl chloride) (PVC) as the reference. The results show that this new polyurethane had relatively lower platelet adhesion and limited shape change for the attached platelets compared to PVC. The clotting time of the materials in contact with platelet poor plasma (PPP) was 99, 75, and 62 s and in contact with PRP was more than 240, 100, and 86 s for new polyurethane, PVC, and glass, respectively. This new phospholipid polyurethane is expected to have wide applications as coating or structural material for blood-contacting medical equipment due to its outstanding haemocompatibility and excellent mechanical strength.

Biocompatible Materials↗
PubMed1996

[Study on the effect of preoperative vaginal douche].

In this study, the effect of pre-operative douche giving to 31 patients with myoma of the uterus was observed. Group A was given douche daily for one day and group B was given douche daily for four days before operation. Through the bacterial culture of douche suab and observation after operation, there was no significant difference between group A and B (P > 0.05). The results estimated that douches before operation should be reduced.

Adult↗
PubMed1995

Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation.

The complete human BCR gene (152-141 nt) on chromosome 22 and greater than 80% of the human ABL gene (179-512 nt) on chromosome 9 have been sequenced from mapped cosmid and plasmid clones via a shotgun strategy. Because these two chromosomes are translocated with breakpoints within the BCR and ABL genes in Philadelphia chromosome-positive leukemias, knowledge of these sequences also might provide insight into the validity of various theories of chromosomal rearrangements. Comparison of these genes with their cDNA sequences reveal the positions of 23 BCR exons and putative alternative BCR first and second exons, as well as the common ABL exons 2-11, respectively. Additionally, these regions include the alternative ABL first exons 1b and 1a, a new gene 5' to the first ABL exon, and an open reading frame with homology to an EST within the BCR fourth intron. Further analysis reveals an Alu homology of 38.83 and 39.35% for the BCR and ABL genes, respectively, with other repeat elements present to a lesser extent. Four new Philadelphia chromosome translocation breakpoints from chronic myelogenous leukemia patients also were sequenced, and the positions of these and several other previously sequenced breakpoints now have been mapped precisely, although no consistent breakpoint features immediately were apparent. Comparative analysis of genomic sequences encompassing the murine homologues to the human ABL exons 1b and 1a, as well as regions encompassing the ABL exons 2 and 3, reveals that although there is a high degree of homology in their corresponding exons and promoter regions, these two vertebrate species show a striking lack of homology outside these regions.

Animals↗