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Biomedical subjects

Y F Wang

Publications and source records attributed to Y F Wang.

At least 73 records · Page 4Linked to original sources
PubMed1999

Control systems of gastrointestinal motility are immature at birth in dogs.

Networks of interstitial cells of Cajal (ICC) in the myenteric plexus (Myp) or circular muscle (CM) function as pacemakers for gastrointestinal slow waves. ICC in contact with muscle and closely associated with nerves in the CM may mediate inhibitory neurotransmission. We wondered if ICC in Myp and CM and their connections are immature at birth and mature first in the proximal gut in association with nerves. Tissues from lower esophageal sphincter (LES), pylorus (PYL), small intestine (SI) and colon (CO) of 18 term fetal dogs taken from six females were fixed and prepared for ultrastructural examination and studied. Ganglia were present where expected in the Myp and submucous plexus (SMP). ICC cells were present in the Myp of PYL, SI and CO and appeared to have normal relationships to the outer border of CM as in adults. ICC in CM were found associated with nerves in the LES and in PYL, but not in SI or CO. However, axons in CM were everywhere usually free of glial covering, indicating ongoing migration or development. No organized deep muscular plexus (DMP) in SI or submuscular plexus (SP) in colon was present. Visible gap junctions were absent everywhere except for very rare ones between circular muscle cells. We conclude that at birth the neural and ICC networks of CM are more immature in intestine and colon than in oesophagus and stomach. Development of nerve and ICC of CM in oesophagus and stomach apparently precedes that in the remaining gut. However networks in these regions have not achieved adult organization and ICC and smooth muscle cells are anatomically poorly coupled. These findings suggest the reasons that gut motility at birth will not be adult in pattern are because ICC, nerve and muscle control systems are not fully differentiated. Further developmental delays in ICC and nerve maturation could have serious consequences for feeding of infant animals.

Animals↗
PubMed1999

Structural and kinetic analysis of drug resistant mutants of HIV-1 protease.

Mutants of HIV-1 protease that are commonly selected on exposure to different drugs, V82S, G48V, N88D and L90M, showed reduced catalytic activity compared to the wild-type protease on cleavage site peptides, CA-p2, p6pol-PR and PR-RT, critical for viral maturation. Mutant V82S is the least active (2-20% of wild-type protease), mutants N88D, R8Q, and L90M exhibit activities ranging from 20 to 40% and G48V from 50 to 80% of the wild-type activity. In contrast, D30N is variable in its activity on different substrates (10-110% of wild-type), with the PR-RT site being the most affected. Mutants K45I and M46L, usually selected in combination with other mutations, showed activities that are similar to (60-110%) or greater than (110-530%) wild-type, respectively. No direct relationship was observed between catalytic activity, inhibition, and structural stability. The mutants D30N and V82S were similar to wild-type protease in their stability toward urea denaturation, while R8Q, G48V, and L90M showed 1.5 to 2.7-fold decreased stability, and N88D and K45I showed 1.6 to 1.7-fold increased stability. The crystal structures of R8Q, K45I and L90M mutants complexed with a CA-p2 analog inhibitor were determined at 2.0, 1.55 and 1.88 A resolution, respectively, and compared to the wild-type structure. The intersubunit hydrophobic contacts observed in the crystal structures are in good agreement with the relative structural stability of the mutant proteases. All these results suggest that viral resistance does not arise by a single mechanism.

Catalytic Domain↗
PubMed1999

Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury.

BACKGROUND AND PURPOSE: Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte beta2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role of Mac-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in mice genetically engineered with a specific deficiency in Mac-1. METHODS: Transient focal ischemia/reperfusion was induced by occluding the left middle cerebral artery for 3 hours followed by a 21-hour reperfusion period in Mac-1-deficient (n=12) and wild-type (n=11) mice. Regional cerebral blood flow was determined with a laser-Doppler flowmeter. Brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct volume. Neutrophil accumulation was determined by staining the brain sections with dichloroacetate esterase to identify neutrophils. RESULTS: Compared with the wild-type cohort, Mac-1-deficient mice had a 26% reduction in infarction volume (P<0.05). This was associated with a 50%, but statistically insignificant, reduction in the number of extravasated neutrophils in the infarcted areas of the brains in the mutant mice. There were no differences in regional cerebral blood flow between the 2 groups. CONCLUSIONS: Mac-1 deficiency reduces neutrophil infiltration and cerebral cell death after transient focal cerebral ischemia. This finding may be related to a reduction in neutrophil extravasation in Mac-1-deficient mice.

Animals↗
PubMed1999

Retrospective analysis of 196 patients with suspected pulmonary thromboembolism.

BACKGROUND: There has not been a statistical analysis reporting on patients with pulmonary thromboembolism (PE) in Taiwan. To identify the most common manifestations in patients with PE in Taiwan, we conducted this retrospective study. METHODS: We collected and analyzed the medical records of 196 patients (53 men, mean age, 60 years; 143 women, mean age, 46 years) whose clinical symptoms and signs, chest radiographs and lung scan findings were suggestive of PE. Conventional chest radiography was performed 24 hours to 48 hours before lung scans. The radiopharmaceuticals used in lung scans were 133Xenon for ventilation studies and 99mTechnetium macroaggregated albumin for perfusion studies. All patients had received anticoagulant therapy (heparin and coumadin) to improve PE. RESULTS: The two most common symptoms and signs of PE in the 196 patients were dyspnea (172/196, 87.8%) and tachypnea (176/196, 89.8%). The most common abnormal finding on chest radiography was increased lung markings, which were present in about 36.7% (72/196) of patients. Lung scans showed two or more, large, mismatched, segmental defects (high probability of PE) in both lungs in about 88.8% (174/196) of patients. After anticoagulant therapy, PE, as seen on lung scans, was resolved within four weeks in approximately 93.9% (184/196) of patients. CONCLUSIONS: In Taiwan, a woman aged 40 to 50 years, with no prior history of other medical problems or surgical procedures, with sudden onset of dyspnea or tachypnea, normal or increased lung markings on chest radiography and two or more large mismatched segmental defects on lung scans, is at greatest risk of developing PE. Most patients with PE showed a good response to anticoagulant therapy within four weeks.

Adolescent↗
PubMed1999

Alpha-adrenoceptors in canine mesenteric artery are predominantly 1A subtype: pharmacological and immunochemical evidence.

We wanted to determine which alpha-adrenoceptor subtypes mediate phenylephrine (PE) contraction of dog mesenteric artery in vitro. We studied antagonisms in response to prazosin, 2-(2, 6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane, 5-methylurapidil, N-[2-(2-cyclopropyl methoxy phenoxy)ethyl]5-chloro-alpha,alpha-dimethyl-1H-indole-3-ethanamine HCl (RS 17053), 8-3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl)-3-methyl-4 -oxo-22-phenyl-4H-1-benzopyran 2HCl [SB216469 (Rec 15/2739)], BMY 7378, 8-[2-(1,4-benzodioxan-2-ylmethylamino)ethyl]8-azaspirol++ + [4,5]decane-7,9-dione HCl, MDL 72832, and 7-chloro-2-bromo-3,4,5, 6-tetrahydro-4-methylfurol[4,3,2-ef]3-benzapine. pK(B) values for prazosin, 5-methylurapidil, MDL 72832, and RS-17053 were consistent with action on alpha(1A)-adrenoceptors but decreased with concentration. pK(B) values (9.6) for Rec 15/2739 (alpha(1L/1A)-adrenoceptor selective) were constant. Antagonism by BMY 7378, 7-chloro-2-bromo-3,4,5,6-tetrahydro-4-methylfurol[4,3, 2-ef]3-benzapine, and 8-[2-(1, 4-benzodioxan-2-ylmethylamino)ethyl]8-azaspirol[4,5]de cane-7,9-dione HCl gave pK(B) values between those expected for alpha(1A)- and alpha(1D)-adrenoceptors. Chloroethylclonidine (100 microM) shifted EC(50) values for PE rightward and decreased E(max) values but left large residual responses. After 100 microM chloroethylclonidine, either BMY 7378 (100 nM) or RS-17053 (300 nM) increased EC(50) values for PE contractions with pK(B) values like those of controls. At 6 nM, phenoxybenzamine increased the EC(50) values and reduced E(max) values; prior Rec 15/2739, but not prior BMY 7378, protected receptors against inactivation. An antibody against the alpha(1B)-adrenoceptors immunostained muscle of aorta but not mesenteric artery. We conclude that dog mesenteric artery contains alpha(1A)-adrenoceptors. Discrepancies among responses expected if only these receptors are present may result from pleiotropic functional effects at this receptor and the presence of alpha(1L)-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Male reproductive health research needs and research agenda: Asian and Chinese perspective.

Research that addresses male reproductive health should assist in the development of reproductive health programmes and policy; identify and test new leads in male contraceptive technology; establish effective male involvement initiatives which are likely to have a positive impact on the reproductive health of men and women; guide the allocation of health care resources to ensure cost-effectiveness of interventions; generate new knowledge, develop diagnostic technology in reproductive health and offer optimal treatment/care regimens. In considering the needs and demands of male reproductive health research in Asia and the Pacific, the following six research topics are recommended as the priority research areas: male contraceptive technology; male reproductive health behaviour and male adolescent reproductive health; male reproductive aging including male menopause and other diseases; male RTIs, STDs, HIV/AIDS; prevalence, management and prevention of male infertility; environment and semen quality and other male reproductive problems. One of the major challenges now facing us is the elaboration of a comprehensive, yet realistic male reproductive health research agenda that reflect the needs and demands of Asian developing countries. To this end, to make use of an interdisciplinary approach is of strategic importance. The most creative insights and productive leads are likely to emerge from a research team that is interdisciplinary especially in the field of reproductive health.

Adolescent↗
PubMed1999

At the crossroad of conception and infection: initiatives for immunoglobulin-based contraceptive R & D.

Better understanding of the immunological mechanisms implying the insemination and the infertility of some men and women is needed and crucial to the development of an effective immunocontraceptive method. To provide good protection against conception or infection, and avoid any possible and unexpected complications which immunocontraceptive "vaccine" may arise of, it seems the right time for scientists to create a virtually new thinking for this extremely urgent and important issue. This conceptual article describes our original thoughts of the future development of immunocontraceptives, preferably, based on immunoglobulins rather than vaccines, against human sperm specific antigens and seminal plasma immunosuppressive factors. Its general correctness, advantages and feasibility for fertility regulation and prevention of infection are discussed.

Anti-Infective Agents↗
PubMed1999

[Effect of selective lesions in hypothalamus on bilateral synchronized bursts of rat oxytocin neurons].

In order to clarify the location of the center for synchronized milk-ejection bursts of magnocellular oxytocin neurons in the hypothalamus, the bursts of these neurons were recorded extracellularly in lactating rats with selectively-cutting lesions of the middle brain or hypothalamus. Results showed that unilateral transection of the middle midbrain above the ventral tegmentum did not block the synchronized bursts on both sides; however, the synchronized bursts disappeared after unilateral transection through the middle of the medial hypothalamus. These results suggest that the area from the middle part of the midbrain to that of the hypothalamus does play a crucial role in the synchronized milk-ejection burst.

Animals↗
PubMed1999

[Quantitative stereologic analysis of metabolize dynamic of protein and DNA during somatic embryogensis in Lycium barbarum L].

The protein and DNA content in somatic embryos of Lycium barbarum L were analysed using quantitative stereologicai procedure formed from Cell Morphometry. The photos were transformed into digital images by the Sharp JX-610 scanner. Then the quantity of protein and DNA was count applying digital images processing software. By the result we discuss the relationship between changes in protein and DNA metabolize dynamic and somatic embryogensis.

Culture Techniques↗
PubMed1998

Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic alpha2-adrenoceptors.

It has been shown that noradrenergic activation has great influence on the activities of hypothalamic supraoptic neurons. No direct evidence has been reported on the presynaptic effects of adrenoceptors in the actions of noradrenaline on supraoptic neurons, although postsynaptic mechanisms have been studied extensively. In the present study, we explored presynaptic effects of noradrenaline on the supraoptic neurons by measuring spontaneous inhibitory postsynaptic currents (IPSC) with the whole-cell patch-clamp technique. Noradrenaline reduced the frequency of IPSCs in a dose-dependent (10(-9) to 10(-3) M) and reversible manner. Noradrenaline did not affect the amplitude of IPSCs at concentrations of 10(-9) to 10(-5) M, but reduced the amplitude of IPSCs at high concentrations (10(-4) and 10(-3) M). The inhibitory effects of noradrenaline were mimicked by the alpha2-agonist clonidine (10(-4) M), but not by the alpha1-agonist methoxamine (10(-4) M) nor by the beta-agonist isoproterenol (10(-4) M). Moreover, the inhibitory effects of noradrenaline on IPSCs were blocked by the non-selective alpha antagonist phentolamine (10(-4) M) or the selective alpha2-antagonist yohimbine (10(-4) M), but not by the alpha1-antagonist prazosin (10(-4) M). These results suggest that noradrena-line inhibits release of GABA from the presynaptic GABAergic terminals of the supraoptic neurons by activating presynaptic alpha2-adrenoceptors and such presynaptic mechanisms may play a role in the excitatory control of SON neurons by noradrenergic neurons.

Adrenergic Agents↗
PubMed1998

Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling.

The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-beta signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 A resolution reveals a novel DNA-binding motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue beta hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-beta-responsive genes.

Amino Acid Sequence↗
PubMed1998

ICAM-1 dependent pathway is not involved in the development of neuronal apoptosis after transient focal cerebral ischemia.

We examined brain sections from ICAM-1 deficient mice (-/-) and their nontransgenic littermates (+/+) after focal cerebral ischemia and reperfusion (I/R) for the presence of apoptosis. Despite the reduction in necrosis, the -/- mice had apoptotic cells in the ischemic hemisphere as shown by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining and DNA laddering. ICAM-1 deficiency minimizes necrosis but not apoptosis after temporary MCAO in mice, thereby leaving the potential for delayed neuronal cell death despite ICAM-1 inactivation.

Animals↗
PubMed1998

Colocalization of inhibitory mediators, NO, VIP and galanin, in canine enteric nerves.

The colocalization of three putative inhibitory mediators of enteric nerves, vasoactive intestinal peptide (VIP), galanin (GAL) and nitric oxide synthase (nNOS), was examined in the myenteric plexus of canine antrum, intestine and colon. Many ileal and colonic neurons contained nNOS-immunoreactive (nNOS-IR) activity with some also containing VIP-IR; only a few neurons also contained GAL-IR. Ileal and colonic VIP-IR nerves often appeared to be interneurons innervating nNOS nerves. Many antral neurons contained VIP-IR with nearly all also containing GAL-IR. A few also contained nNOS-IR. The predominance of nNOS-IR neurons relative to VIP-IR and GAL-IR neurons in the ileal and colonic, but not the antral, myenteric plexus is consistent with NO being the primary inhibitory mediator in the intestine but not in the antrum.

Animals↗
PubMed1998

Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation.

The potential of most N-methyl-D-aspartate antagonists as neuroprotectants is limited by side effects. We previously reported that memantine is an open-channel N-methyl-D-aspartate blocker with a faster off-rate than many uncompetitive N-methyl-D-aspartate antagonists such as dizocilpine maleate. This parameter correlated with memantine's known clinical tolerability in humans with Parkinson's disease. Memantine is the only N-methyl-D-aspartate antagonist that has been used clinically for excitotoxic disorders at neuroprotective doses. Therefore, we wanted to investigate further the basis of its clinical efficacy, safety, and tolerability. Here we show for the first time for any clinically-tolerated N-methyl-D-aspartate antagonist that memantine significantly reduces infarct size when administered up to 2 h after induction of hypoxia/ischemia in immature and adult rats. We found that at neuroprotective concentrations memantine results in few adverse side effects. Compared to dizocilpine maleate, memantine displayed virtually no effects on Morris water maze performance or on neuronal vacuolation. At concentrations similar to those in brain following clinical administration, memantine (6-10 microM) did not attenuate long-term potentiation in hippocampal slices and substantially spared the N-methyl-D-aspartate component of excitatory postsynaptic currents, while dizocilpine maleate (6-10 microM) or D-2-amino-5-phosphovalerate (50 microM) completely blocked these phenomena. We suggest that the favorable kinetics of memantine interaction with N-methyl-D-aspartate channels may be partly responsible for its high index of therapeutic safety, and make memantine a candidate drug for use in many N-methyl-D-aspartate receptor-mediated human CNS disorders.

Animals↗
PubMed1998

Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice.

Intravenous tissue plasminogen activator (tPA) is used to treat acute stroke because of its thrombolytic activity and its ability to restore circulation to the brain. However, this protease also promotes neurodegeneration after intracerebral injection of excitotoxins such as glutamate, and neuronal damage after a cerebral infarct is thought to be mediated by excitotoxins. To investigate the effects of tPA on cerebral viability during ischemia/reperfusion, we occluded the middle cerebral artery in wild-type and tPA-deficient mice with an intravascular filament. This procedure allowed us to examine the role of tPA in ischemia, independent of its effect as a thrombolytic agent. tPA-deficient mice exhibited approximately 50% smaller cerebral infarcts than wild-type mice. Intravenous injection of tPA into tPA-/- or wild-type mice produced larger infarcts, indicating that tPA can increase stroke-induced injury. Since tPA promotes desirable (thrombolytic) as well as undesirable (neurotoxic) outcomes during stroke, future therapies should be aimed at countering the excitotoxic damage of tPA to afford even better neuroprotection after an acute cerebral infarct.

Animals↗
PubMed1998

Myogenic nitric oxide synthase activity in canine lower oesophageal sphincter: morphological and functional evidence.

1. Studies on canine lower oesophageal sphincter (LOS) evaluated the existence and function of a myogenic, nitric oxide synthase (NOS) by use of immunocytochemistry for NOS isozymes, NADPH-d histochemistry, [3H]-L-arginine to [3H]-L-citrulline transformation. In addition, functional studies in the muscle bath were performed. 2. Smooth muscle bundles or freshly isolated smooth muscle cells of LOS were NADPH-d reactive but did not recognize some antibodies against neural, endothelial or inducible NOS. NADPH-d reactivity and immunoreactivity to a neural NOS antibody were colocalized in LOS enteric nerves. Muscle plasma membrane-enriched fractions from fresh and cultured LOS cells converted [3H]-L-arginine to [3H]-L-citrulline; activity was mostly Ca2+/calmodulin-dependent. 3. N-Nitro-L-arginine (L-NOARG) persistently increased tone (blocked by L-arginine) in muscle strips despite blockade of nerve function. Nifedipine prevented or abolished L-NOARG-induced, but not carbachol-induced, contraction showing that tone increase by L-NOARG required functional L-Ca channels. 4. Membrane-bound, myogenic NOS in canine LOS may release NO continuously when Ca2+ entry through L-Ca channels occurs under physiological conditions and thereby modulate tone in LOS.

Animals↗
PubMed1998

Differences in the intracellular localization and fate of herpes simplex virus tegument proteins early in the infection of Vero cells.

The fate of herpes simplex virus 1 (HSV-1) tegument proteins during infection in Vero cells was investigated immunochemically. Input virion-associated VP13/14 and VP16 localized to the nucleus early in infection, while VP1/2 localized to the nuclear envelope of the cell and VP22 could not be detected using monoclonal antibody P43. Western blotting suggested that virion-associated VP13/14, VP16 and VP22 were stable in infected cells whereas VP1/2 appeared to be processed or modified. Further studies showed that P43 recognized a phosphorylation-sensitive epitope in VP22 and suggested that virion-associated VP22 was phosphorylated upon entry to the cell. VP13/14 and VP16 were easily extracted from cells early in infection whereas VP22 was largely insoluble. Phosphatase treatment of soluble extracts caused a shift in the molecular mass of VP16 showing it was phosphorylated. As infection progressed VP16 was observed in discrete nuclear compartments where it co-localized with ICP8 and the capsid-associated protein VP22a. VP13/14 was also observed in the nucleus. P43 immunostaining appeared around 6 h post-infection as punctate nuclear foci which often localized to the edge of VP16-immunoreactive areas. Punctate P43 cytoplasmic staining appeared around 12 h post-infection. By 18 h the nuclear pattern had disappeared and an extensive cytoplasmic stain was observed which closely overlapped that of other tegument proteins. On the basis of these data we suggest that virion-associated VP22 is phosphorylated upon entry of the virus into the cell and that unphosphorylated VP22, which is preferentially recognized by P43, becomes available later in infection, initially in the nucleus, for packaging into virions.

Animals↗