Biomedical subjects

H Wong

Publications and source records attributed to H Wong.

At least 55 records · Page 3Linked to original sources

PubMed2000

Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain.

The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally stimulated gastric acid secretion was studied using immunoneutralization with PYY antibody in urethan-anesthetized rats. Gastric acid secretion (59+/-7 micromol/90 min) stimulated by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by 52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol. kg(-1) x h(-1) PYY, respectively. PYY or PYY(3-36) (2.4 pmol/rat) injected intracisternally also inhibited the acid response to intracisternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY(3-36) by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol x kg(-1) x h(-1)). When injected intracisternally, the PYY antibody (280 microg/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol x kg(-1) x h(-1))-induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%, respectively. These results provide supporting evidence that peripheral PYY inhibits central vagal stimulation of gastric acid secretion through an action in the brain.

Animals↗

PubMed2000

Disposition of valproic acid in maternal, fetal, and newborn sheep. I: placental transfer, plasma protein binding, and clearance.

Separate 24-h maternal and fetal infusions of valproic acid (VPA) were administered to five pregnant sheep at 125 to 138 days gestation (term approximately 145 days) to determine maternal-fetal disposition. The pharmacokinetics of VPA were also investigated in five newborn 1-day-old lambs after a 6-h drug infusion. Plasma, urine, and amniotic and fetal tracheal fluid samples were analyzed for VPA using gas chromatography-mass spectrometry. During maternal drug infusion, the average steady-state fetal/maternal unbound VPA plasma concentration ratio was 0.81 +/- 0.09. Unbound maternal-to-fetal VPA placental clearance (69.0 +/- 20.2 ml/min/kg) was similar to that in the other direction (61.9 +/- 24.2 ml/min/kg); this indicates passive placental diffusion and intermediate placental permeability of VPA in sheep. Newborn unbound VPA clearance (0.66 +/- 0.28 ml/min/kg) was much lower than in the mother (5.4 +/- 2.7 ml/min/kg) or the fetus (62.1 +/- 22.4 ml/min/kg), and exhibited pronounced Michaelis-Menten characteristics. The elimination half-life of the drug was much longer in the newborn (18.6 +/- 2.6 h) relative to the mother (5.6 +/- 1.4 h) and the fetus (4.6 +/- 1.9 h). Thus, VPA elimination in newborn lambs is much slower as compared with adult sheep, a situation similar to that in humans. Plasma protein binding of VPA was saturable, with similar VPA binding capacities and affinities in maternal and fetal plasma. VPA was extensively displaced from binding sites in the newborn lamb during the first 1 to 2 days of life, possibly because of increased plasma free fatty acid concentrations at birth. Thereafter, newborn plasma appeared to have a similar VPA binding capacity but lower affinity compared with the mother and the fetus.

Animals↗

PubMed2000

Disposition of valproic acid in maternal, fetal, and newborn sheep. II: metabolism and renal elimination.

Metabolism and renal excretion of valproic acid (VPA) were examined in maternal, fetal, and newborn sheep to identify the underlying reasons for the previously observed reduced VPA clearance in newborn lambs. Plasma and urine from VPA infusion studies in maternal, fetal, and newborn sheep were analyzed for VPA and its metabolites [VPA-glucuronide; beta-oxidation products: (E)-2-ene, (E)-3-ene, and 3-keto VPA; hydroxylated metabolites: 3-hydroxy, 4-hydroxy, and 5-hydroxy VPA (5-OH VPA); and 4-ene VPA, 4-keto VPA, 2-propylglutaric acid, and 2-propylsuccinic acid] using gas chromatography-mass spectrometry. All measured metabolites were detectable in maternal and fetal plasma, with 3-keto and 5-OH VPA being at higher concentrations in the fetus. Plasma concentrations of (E)-2-ene, (E)-3-ene, 3-keto, and 5-OH VPA were higher in the newborn compared with the mother, whereas those of the other metabolites were similar. A smaller percentage of the dose was excreted as VPA-glucuronide in newborn lamb urine (28.3 +/- 12.0%) compared with the mother (77.0 +/- 7.8%). Similarly, a lower fraction of the dose was excreted unchanged in newborn urine (11.0 +/- 5.8%) relative to the urine of the mother (19.3 +/- 5.8%); however, significantly larger percentages were excreted as (E)-2-ene (0.11 +/- 0.04 versus 0.02 +/- 0.01%), 3-keto (11.6 +/- 3.5 versus 1. 6 +/- 0.8%), 4-hydroxy (6.1 +/- 3.2 versus 2.3 +/- 1.3%), and 5-OH VPA (2.2 +/- 0.6 versus. 0.8 +/- 0.6%). The major reason for the reduced VPA elimination in newborn lambs appears to be impaired renal excretion and glucuronidation capacity. As a result, a larger fraction of the dose is channeled to beta-oxidation and hydroxylation pathways. The beta-oxidation activities are high at birth; this may explain the high plasma concentrations of (E)-2-ene and 3-keto VPA observed in newborn lambs and human newborns exposed to VPA.

Animals↗

PubMed2000

Ontogeny of valproic acid disposition and metabolism: a developmental study in postnatal lambs and adult sheep.

The ontogeny of valproic acid (VPA) disposition and metabolism was investigated in developing lambs and adult sheep (Dorset or Suffolk breed). Specifically, we wished to investigate the role of glucuronidation and beta-oxidation on VPA elimination during development. Catheters were implanted in a carotid artery, a jugular vein, and the urinary bladder in 10-day-old (10 d; n = 8), 1-month-old (1 M; n = 4), and 2-month-old lambs (2 M; n = 5). In adult sheep (n = 5), catheters were implanted in a femoral artery and vein. After the administration of a 10 mg/kg VPA i.v. bolus, serial blood samples and cumulative urine samples were collected for 36 h in the adult ewes and for 72 h in the lambs. Due to saturable protein binding, age-related differences in VPA clearance were more obvious when examining the total body clearance of unbound drug (Cl(u)tb). Mean Cl(u)tb increased significantly with age up to 2 months (10 d = 2.65 +/- 1.16 ml/min/kg; 1 M = 5.11 +/- 2.49 ml/min/kg; 2 M = 12.84 +/- 3.88 ml/min/kg) before decreasing to adult levels (7.73 +/- 2.64 ml/min/kg). Similarly, the urinary recovery of the major metabolite, VPA-glucuronide, was significantly less in 10 d lambs (29.2 +/- 16.0% of the dose) when compared with the adult and 2 M groups (both approximately 74% of the dose). No differences with age were observed in the portion of the dose excreted as the beta-oxidation metabolite, 2-n-propyl-3-oxopentanoic acid. The results suggest that alterations in Cl(u)tb with age may be attributable to postnatal development of enzymes involved in VPA glucuronidation.

Age Factors↗

PubMed2000

Lipoprotein lipase- and hepatic triglyceride lipase- promoted very low density lipoprotein degradation proceeds via an apolipoprotein E-dependent mechanism.

Apolipoprotein E (apoE) is the primary recognition signal on triglyceride-rich lipoproteins responsible for interacting with low density lipoprotein (LDL) receptors and LDL receptor-related protein (LRP). It has been shown that lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) promote receptor-mediated uptake and degradation of very low density lipoproteins (VLDL) and remnant particles, possibly by directly binding to lipoprotein receptors. In this study we have investigated the requirement for apoE in lipase-stimulated VLDL degradation. We compared binding and degradation of normal and apoE-depleted human VLDL and apoE knockout mouse VLDL in human foreskin fibroblasts. Surface binding at 37 degrees C of apoE knockout VLDL was greater than that of normal VLDL by 3- and 40-fold, respectively, in the presence of LPL and HTGL. In spite of the greater stimulation of surface binding, lipase-stimulated degradation of apoE knockout mouse VLDL was significantly lower than that of normal VLDL (30, 30, and 80%, respectively, for control, LPL, and HTGL treatments). In the presence of LPL and HTGL, surface binding of apoE-depleted human VLDL was, respectively, 40 and 200% of normal VLDL whereas degradation was, respectively, 25 and 50% of normal VLDL. LPL and HTGL stimulated degradation of normal VLDL in a dose-dependent manner and by a LDL receptor-mediated pathway. Maximum stimulation (4-fold) was seen in the presence LPL (1 microgram/ml) or HTGL (3 microgram/ml) in lovastatin-treated cells. On the other hand, degradation of apoE-depleted VLDL was not significantly increased by the presence of lipases even in lovastatin-treated cells. Surface binding of apoE-depleted VLDL to metabolically inactive cells at 4 degrees C was higher in control and HTGL-treated cells, but unchanged in the presence of LPL. Degradation of prebound apoE-depleted VLDL was only 35% as efficient as that of normal VLDL. Surface binding of apoE knockout or apoE-depleted VLDL was to heparin sulfate proteoglycans because it was completely abolished by heparinase treatment. However, apoE appears to be a primary determinant for receptor-mediated VLDL degradation. Our studies suggest that overexpression of LPL or HTGL may not protect against lipoprotein accumulation seen in apoE deficiency.

Animals↗

PubMed1999

Hypothermia decreases excitatory neurotransmitter release in bacterial meningitis in rabbits.

The excitatory neurotransmitters glutamate (GLU) and aspartate (ASP) are involved in the pathogenesis of neuronal injury in meningitis. Based on past findings that the induction of moderate hypothermia (32-34 degrees C) attenuates the release of GLU in ischemic brain injury, this study was designed to detect if the application of moderate hypothermia decreases the release of excitatory amino acids (EAA) from brain tissue of animals with bacterial meningitis. Also examined was whether meningitis induces the expression of 72-kDa heat shock protein (HSP 70) in the cerebellum and how hypothermia affects it, for induction of HSP 70 has been used as a sensitive marker of neuronal stress in other forms of brain injury. Meningitis was induced by injecting Group B Streptococcus (GBS) into the cisterna magnae of rabbits. Antibiotic treatment began 16 h later. At this time the animals were anesthetized, instrumented, and randomized to normothermic (Nor) or hypothermic (Hy) conditions. Temperatures were strictly regimented for the following 10 h while maintaining stable cardiorespiratory parameters. Cerebrospinal fluid (CSF) samples were then withdrawn to measure concentrations of bacteria, protein, and amino acids. Meningitis causes CSF contents of GLU and ASP to increase significantly. Hypothermia treated animals demonstrated a 40-50% reduction in CSF GLU and ASP. Meningitis induced the expression of HSP 70 in the cerebellum while hypothermic animals experienced a significant decrease HSP 70 induction. These data demonstrate that hypothermia produces an attenuation of the release of excitatory neurotransmitters in meningitis and suggest that this treatment may attenuate neuronal stress.

Animals↗

PubMed1999

Trafficking of proteinase-activated receptor-2 and beta-arrestin-1 tagged with green fluorescent protein. beta-Arrestin-dependent endocytosis of a proteinase receptor.

Proteases cleave proteinase-activated receptors (PARs) to expose N-terminal tethered ligands that bind and activate the cleaved receptors. The tethered ligand, once exposed, is always available to interact with its binding site. Thus, efficient mechanisms must prevent continuous activation, including receptor phosphorylation and uncoupling from G-proteins, receptor endocytosis, and lysosomal degradation. beta-Arrestins mediate uncoupling and endocytosis of certain neurotransmitter receptors, which are activated in a reversible manner. However, the role of beta-arrestins in trafficking of PARs, which are irreversibly activated, and the effects of proteases on the subcellular distribution of beta-arrestins have not been examined. We studied trafficking of PAR2 and beta-arrestin1 coupled to green fluorescent protein. Trypsin induced the following: (a) redistribution of beta-arrestin1 from the cytosol to the plasma membrane, where it co-localized with PAR2; (b) internalization of beta-arrestin1 and PAR2 into the same early endosomes; (c) redistribution of beta-arrestin1 to the cytosol concurrent with PAR2 translocation to lysosomes; and (d) mobilization of PAR2 from the Golgi apparatus to the plasma membrane. Overexpression of a C-terminal fragment of beta-arrestin-319-418, which interacts constitutively with clathrin but does not bind receptors, inhibited agonist-induced endocytosis of PAR2. Our results show that beta-arrestins mediate endocytosis of PAR2 and support a role for beta-arrestins in uncoupling of PARs.

Animals↗

PubMed1999

Substance P-induced trafficking of beta-arrestins. The role of beta-arrestins in endocytosis of the neurokinin-1 receptor.

Agonist-induced redistribution of G-protein-coupled receptors (GPCRs) and beta-arrestins determines the subsequent cellular responsiveness to agonists and is important for signal transduction. We examined substance P (SP)-induced trafficking of beta-arrestin1 and the neurokinin-1 receptor (NK1R) in KNRK cells in real time using green fluorescent protein. Green fluorescent protein did not alter function or localization of the NK1R or beta-arrestin1. SP induced (a) striking and rapid (<1 min) translocation of beta-arrestin1 from the cytosol to the plasma membrane, which preceded NK1R endocytosis; (b) redistribution of the NK1R and beta-arrestin1 into the same endosomes containing SP and the transferrin receptor (2-10 min); (c) prolonged colocalization of the NK1R and beta-arrestin1 in endosomes (>60 min); (d) gradual resumption of the steady state distribution of the NK1R at the plasma membrane and beta-arrestin1 in the cytosol (4-6 h). SP stimulated a similar redistribution of immunoreactive beta-arrestin1 and beta-arrestin2. In contrast, SP did not affect Galphaq/11 distribution, which remained at the plasma membrane. Expression of the dominant negative beta-arrestin319-418 inhibited SP-induced endocytosis of the NK1R. Thus, SP induces rapid translocation of beta-arrestins to the plasma membrane, where they participate in NK1R endocytosis. beta-Arrestins colocalize with the NK1R in endosomes until the NK1R recycles and beta-arrestins return to the cytosol.

Animals↗

PubMed1999

An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system.

This work was prompted by the accidental observation that a newly developed, affinity purified polyclonal antibody against the C-terminus of the neuropeptide tyrosine (NPY) Y1-receptor protein decorates degenerating fibers in the central nervous system (CNS). This staining did not appear in control animals in which the antibody marked perikarya and dendrites at previously described locations [X. Zhang, L. Bao, Z.-Q. Xu, J. Kopp, U. Arvidsson, R. Elde, T. Hökfelt, Localization of neuropeptide Y Y1-receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurons, Proc. Natl. Acad. Sci. USA 91 (1994) 11738-11742]. Three models of experimental lesions were studied: sciatic nerve transection, spinal cord transection and parietal cortex thermocoagulation. In each model, animals were divided in groups (n=2) and processed for indirect immunofluorescence at different time intervals up to 28 days post-lesion (PL) (see below). All three experimental lesions produced a very intense immunolabeling of fibers in the projection pathways of the lesioned structures, strongly reminding of Wallerian degeneration (WD). In the sciatic nerve, the staining first appeared on day 1 PL, was strongly increased on day 3 PL, then declined after 7 days and had almost completely disappeared after 14 days. In the CNS, the staining appeared later and was first observed on day 3 PL and remained for a longer period, thus showing different time courses in the brain and spinal cord as compared to the sciatic nerve. The labeling was completely abolished, both in the CNS and in the sciatic nerve, by pre-incubation of the Y1-R antibody with the immunogenic peptide at a dilution of 10-6 M. The appearance of the staining and its time course strongly suggest that the process was related to degenerating axons. Although the protein actually detected remains to be determined, it is suggested that the staining ability of this antibody could be used as a positive marker of axonal degeneration following experimental or naturally occurring lesions of the nervous system.

Animals↗

PubMed1999

Expression of cholecystokinin A receptors in neurons innervating the rat stomach and intestine.

BACKGROUND & AIMS: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. METHODS: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. RESULTS: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor-transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK-A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. CONCLUSIONS: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.

Amino Acid Sequence↗

PubMed1999

Market factors and the availability of community pharmacies.

The purpose of this study was to examine the relationships between the availability of community pharmacies and 4 types of market factors. A composite data set was created that linked, at the county level, data on: (1) type and number of pharmacies; (2) population characteristics; (3) payer variables; (4) health care system factors; and (5) competitive factors. In this exploratory study, secondary data were used to assess the association between the availability of community pharmacies and the influence of market factors. To assess the market influences on availability of community pharmacies, 2 regressions were performed. In 1 model, the number of community pharmacies per 10,000 population was the dependent variable, whereas the dependent variable in the other regression was the proportion of independently owned community pharmacies. The independent variables in each regression were the market factors--population characteristics, payer variables, health care system factors, and competitive variables. Squared terms were included for 8 of 15 market factors to account for nonlinearities in the relationships. Multiple market factors were correlated with both the number of community pharmacies and the proportion of independently owned pharmacies in an area. Several of the relationships were not linear and changed direction within the range of data. Counties with either a low or a high percentage of elderly people had fewer pharmacies and a lower proportion of independently owned pharmacies compared with counties with a moderate percentage of elderly people. Counties that were scarcely or highly rural had fewer community pharmacies but a higher proportion of independently owned pharmacies than counties that were moderately rural. Areas with a greater percentage of the population earning less than the poverty level had more pharmacies, especially independently owned ones. Fewer community pharmacies were found in areas with higher health maintenance organization penetration rates. The number of hospital admissions was positively associated with the number of pharmacies but negatively associated with the proportion of independently owned pharmacies. The availability of community pharmacies varies across the country. In light of the trend toward fewer independently owned pharmacies, potential problems in accessing pharmacy services could develop in certain areas, including those that are highly rural and those with a high percentage of people earning less than the poverty level. Future research and policy issues are identified.

Data Collection↗

PubMed1999

Somatostatin receptor subtype 2A expression in the rat retina.

Somatostatin is mainly expressed by sparsely occurring amacrine and interplexiform cells in the retina. In this study, we characterized the expression and cellular localization of one of the somatostatin subtype (sst) receptors, sst2A, in the rat retina. The presence of sst2A receptor messenger RNA in retinal extracts was demonstrated by reverse transcription-polymerase chain reaction using specific primers to detect the sst2 receptor and its isoforms, sst2A and sst2B. Specific sst2A receptor immunoreactivity was mainly localized to the plasma membrane of several neuronal cell types. In the outer retina, immunoreactivity was localized to cone photoreceptors, horizontal cells, and rod and cone bipolar cells. Double-label experiments showed the co-localization of sst2A receptor and protein kinase C (alpha and beta), a rod bipolar cell marker, and of sst2A receptor and Calbindin-D28k, a horizontal cell marker. In the inner retina, sst2A receptor immunoreactivity occurred in tyrosine hydroxylase-positive amacrine cells; most were of medium to large size. These findings indicate that somatostatin may act at a distance, in a paracrine manner, on several cell types that express the sst2A receptor, and therefore exert a broad modulatory influence on both scotopic and photopic visual pathways.

Animals↗

PubMed1999

Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas.

Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and more strongly correlated with tumour grade. We did not see a close relationship between the levels of expression of MT1-MMP mRNA and amounts of activated gelatinase-A. In situ hybridization localized gelatinase-A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and blood vessels. In contrast, gelatinase-B showed a more restricted pattern of expression; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A, -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovascularization, whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and angiogenesis.

Brain↗

PubMed1999

The effect of decreasing digital image resolution on teledermatology diagnosis.

OBJECTIVE: To determine the effect of degraded digital image resolution (as viewed on a monitor) on the accuracy and confidence of dermatologic interpretation. MATERIALS AND METHODS: Eight dermatologists interpreted 180 clinical cases divided into three Logical Competitor Sets (LCS) (pigmented lesions, non-pigmented lesions, and inflammatory dermatoses). Each case was digitized at three different resolutions. The images were randomized and divided into (9) 60-image sessions. The physicians were completely blinded concerning the image resolution. After 60 seconds per image, the viewer recorded a diagnosis and level of confidence. The resultant ROC curves compared the effect of LCS, level of clinical difficulty, and resolution of the digital image. One-way analysis of variance (ANOVA) compared the curves. RESULTS: The areas beneath the ROC curves did not demonstrate any consistently significant difference between the digital image resolutions for all LCS and levels of difficulty. The only significant effect observed was amongst pigmented lesions (LCS-A) where the ROC curve area was significantly smaller in the easy images at high resolution compared to low and medium resolutions. For all other ROC curve comparisons within LCS-A, at all other levels of difficulty, as well as within the other LCS at all levels of difficulty, none of the differences was significant. CONCLUSION: A 720 x 500 pixel image can be considered equivalent to a 1490 x 1000 pixel image for most store-and-forward teledermatology consultations.

Analysis of Variance↗

PubMed1999

Differential inhibition of insulin and islet amyloid polypeptide secretion by intraislet somatostatin in the isolated perfused human pancreas.

Islet amyloid polypeptide (IAPP) and insulin are co-stored and generally secreted in parallel; however, studies have demonstrated that the IAPP/insulin molar secretory ratio may be altered in response to certain stimuli. Because we previously demonstrated that intraislet somatostatin is an inhibitory regulator of basal insulin secretion in the isolated perfused human pancreas, this study was designed to determine the relative influence on the regulation of IAPP versus insulin secretion. Single-pass perfusion was performed in pancreata obtained from cadaveric organ donors with continuous perfusion of a modified Krebs media with the glucose level maintained at constant 3.9 mM. Intraislet somatostatin was immunoneutralized by the infusion of either a highly sensitive monoclonal somatostatin antibody (SAb) or its FAb fragment (SFAb). Sequential test periods separated by basal periods were performed by infusion of either of the following: glucose, SAb, SFAb, or appropriate controls. IAPP/insulin molar secretory ratio decreased by 33% in response to infusion of either SAb or the SFAb, respectively (p < 0.01), and decreased by 67% in response to glucose infusion (p < 0.01). An alteration of the IAPP/insulin secretory ratio is seen in response to infusion of exogenous glucose or in response to the neutralization of intraislet somatostatin.

Adolescent↗

PubMed1999

Characterization of Moraxella (Branhamella) catarrhalis lbpB, lbpA, and lactoferrin receptor orf3 isogenic mutants.

Pathogenic members of the family Neisseriaceae produce specific receptors to acquire iron from their host's lactoferrin and transferrin. Recently, putative Moraxella catarrhalis lactoferrin receptor genes and a third open reading frame (lbpB, lbpA, and orf3) were cloned and sequenced. We describe the preliminary characterization of isogenic mutants deficient in LbpB, LbpA, or Orf3 protein.

Bacterial Outer Membrane Proteins↗

PubMed1999

Endogenous glucocorticoids released during acute toxic liver injury enhance hepatic IL-10 synthesis and release.

Endogenous glucocorticoids are known to play a role in the regulation of the inflammatory response possibly by modulating pro- and anti-inflammatory cytokine expression. We examined endogenous glucocorticoid secretion, hepatic damage, tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) mRNA expression and release in rats treated with carbon tetrachloride (CCl4) after treatment with vehicle or a glucocorticoid receptor antagonist (RU-486). Rats treated with CCl4 demonstrated striking elevations of plasma corticosterone levels. Inhibition of endogenous glucocorticoid activity by pretreatment with the glucocorticoid receptor antagonist RU-486 resulted in augmented CCl4-mediated hepatotoxicity, as reflected by histology and serum transaminase levels, which were independent of alterations in serum TNF-alpha levels or hepatic mRNA expression. CCl4 treatment resulted in enhanced hepatic IL-10 mRNA expression and elevated serum IL-10 levels, which were markedly attenuated by glucocorticoid receptor blockade. In summary, significant endogenous glucocorticoid release occurs during acute toxic liver injury in the rat and suppresses the inflammatory response independent of effects on TNF-alpha but possibly by upregulating hepatic IL-10 production.

Acute Disease↗

PubMed1999

Intestinal fat-induced inhibition of meal-stimulated gastric acid secretion depends on CCK but not peptide YY.

Fat in small intestine decreases meal-stimulated gastric acid secretion and slows gastric emptying. CCK is a mediator of this inhibitory effect (an enterogastrone). Because intravenously administered peptide YY (PYY) inhibits acid secretion, endogenous PYY released by fat may also be an enterogastrone. Four dogs were equipped with gastric, duodenal, and midgut fistulas. PYY antibody (anti-PYY) at a dose of 0.5 mg/kg or CCK-A receptor antagonist (devazepide) at a dose of 0.1 mg/kg was administered alone or in combination 10 min before the proximal half of the gut was perfused with 60 mM oleate or buffer. Acid secretion and gastric emptying were measured. We found that 1) peptone-induced gastric acid secretion was inhibited by intestinal fat (P < 0.0001), 2) inhibition of acid secretion by intestinal fat was reversed by CCK-A receptor antagonist (P < 0.0001) but not by anti-PYY, and 3) slowing of gastric emptying by fat was reversed by CCK-A antagonist (P < 0. 05) but not by anti-PYY. We concluded that inhibition of peptone meal-induced gastric acid secretion and slowing of gastric emptying by intestinal fat depended on CCK but not on circulating PYY.

Animals↗