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Biomedical subjects

P Kwong

Publications and source records attributed to P Kwong.

11 recordsLinked to original sources
PubMed2001

Pacap stimulation of gonadotropin-II secretion in goldfish pituitary cells: mechanisms of action and interaction with gonadotropin releasing hormone signalling.

Pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been shown to be a hypophysiotropic factor in the goldfish. In this study, we examined the mechanisms of PACAP action on goldfish maturational gonadotropin (GTH-II) release using primary cultures of pituitary cells. The GTH-II response to mammalian PACAP1-38 (mPACAP) was inhibited by a PACAP receptor antagonist suggesting a receptor-mediated action. Addition of either an adenylate cyclase inhibitor or a protein kinase A (PKA) inhibitor reduced the mPACAP-induced GTH-II release. In addition, when GTH-II release was already stimulated by either forskolin or 8-bromo-cAMP (8Br-cAMP), mPACAP did not further increase GTH-II secretion. These results strongly implicated the involvement of an adenylate cyclase/cAMP/PKA pathway in PACAP-stimulated GTH-II release. Although mPACAP induced a rise in intracellular Ca2+ level in identified gonadotropes, results with voltage-sensitive Ca2+ channel inhibitors indicated that the GTH-II responses to mPACAP, forskolin and 8Br-cAMP did not depend upon Ca2+ entry through these channels. Two protein kinase C (PKC) inhibitors did not affect mPACAP-elicited GTH-II release, and mPACAP further increased GTH-II secretion in the presence of PKC activators. These results indicate that PKC-dependent elements are not essential for the stimulatory action of mPACAP in gonadotropes. Interestingly, while GTH-II responses to a stimulatory concentration of mPACAP were additive to responses elicited by maximal effective concentrations of two endogenous gonadotropin releasing hormones (GnRHs), a subthreshold concentration of mPACAP potentiated GnRH and PKC activator stimulation of GTH-II secretion. Similarly, submaximal concentrations of forskolin potentiated the GTH-II response to the PKC activator, tetradecanoyl phorbol acetate. These data suggest that PACAP and its cAMP-dependent signalling mechanisms provide an alternate stimulatory input to goldfish gonadotropes and may influence the effectiveness of the major neuroendocrine control exerted by the PKC-dependent GnRH signalling pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Conformational changes of gp120 in epitopes near the CCR5 binding site are induced by CD4 and a CD4 miniprotein mimetic.

Binding of the T-cell antigen CD4 to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 has been reported to induce conformational rearrangements in the envelope complex that facilitate recognition of the CCR5 coreceptor and consequent viral entry into cells. To better understand the mechanism of virus docking and cell fusion, we developed a three-component gp120-CD4-17b optical biosensor assay to visualize the CD4-induced conformational change of gp120 as seen through envelope binding to a neutralizing human antibody, 17b, which binds to epitopes overlapping the CCR5 binding site. The 17b Fab fragment was immobilized on a dextran sensor surface, and kinetics of gp120 binding were evaluated by both global and linear transformation analyses. Adding soluble CD4 (sCD4) increased the association rate of full-length JR-FL gp120 by 25-fold. This change is consistent with greater exposure of the 17b binding epitope on gp120 when CD4 is bound and correlates with CD4-induced conformational changes in gp120 leading to higher affinity binding to coreceptor. A smaller enhancement of 17b binding by sCD4 was observed with a mutant of gp120, DeltaJR-FL protein, which lacks V1 and V2 variable loops and N- and C-termini. Biosensor results for JR-FL and DeltaJR-FL argue that CD4-induced conformational changes in the equilibrium state of gp120 lead both to movement of V1/V2 loops and to conformational rearrangement in the gp120 core structure and that both of these lead to greater exposure of the coreceptor-binding epitope in gp120. A 17b binding enhancement effect on JR-FL also was observed with a 32-amino acid charybdotoxin miniprotein construct that contains an epitope predicted to mimic the Phe 43/Arg 59 region of CD4 and that competes with CD4 for gp120 binding. Results with this construct argue that CD4-mimicking molecules with surrogate structural elements for the Phe 43/Arg 59 components of CD4 are sufficient to elicit a similar gp120 conformational isomerization as expressed by CD4 itself.

Amino Acid Sequence↗
PubMed1998

Hyaline membrane disease is underreported in a linked birth-infant death certificate database.

OBJECTIVE: This study compared the Missouri State Department of Health linked birth-infant death certificate database and medical records with respect to recording hyaline membrane disease in very low-birth-weight infants. METHODS: We reviewed the records for all 976 infants weighing 500 to 1500 g who were born to St. Louis, Mo, residents in 1989, 1991, and 1992. RESULTS: Eighteen percent of the birth certificates and 54% of the medical records documented hyaline membrane disease, resulting in 34% sensitivity and 99% specificity. CONCLUSIONS: The Missouri State Department of Health birth-infant death certificate database underestimates the incidence of hyaline membrane disease, which suggest that national statistics for the disease are also underestimated.

Birth Certificates↗
PubMed1997

Somatostatin inhibition of growth hormone release in goldfish: possible targets of intracellular mechanisms of action.

Previous studies have demonstrated that growth hormone (GH) release in goldfish is under the stimulatory control of gonadotropin-releasing hormone (GnRH) and dopamine and the inhibitory control of somatostatin (SRIF). GnRH stimulation is mediated through protein kinase C (PKC)- and calcium-dependent mechanisms, whereas dopamine D1 receptor activation increases GH secretion through cyclic (c) AMP-dependent intracellular signal transduction pathways. In this study, the mechanisms of SRIF inhibition on GH secretion were examined using primary cultures of dispersed goldfish pituitary cells in static incubation. Application of 1 microM SRIF inhibited the GH-release responses to 100 nM salmon GnRH, 100 nM chicken GnRH-II, and 1 microM SKF38393, a D1 agonist. These results indicate that inhibitory action of SRIF on stimulated GH release is direct, at the level of the pituitary cells. Addition of SRIF reduced the GH release responses to two activators of PKC (100 microM dioctanoyl glycerol and 100 nM tetradecanoyl phorbol acetate) and to two ionophores (10 microM A23187 and 10 microM ionomycin). Similarly, SRIF abolished the GH responses to an activator of adenylate cyclase (10 microM forskolin), a membrane-permeant cAMP analog (1 mM 8-bromo-cAMP), and a voltage-sensitive calcium channel agonist (1 microM Bay K 8644). Taken together, these observations indicate that the inhibitory actions of SRIF on D1- and GnRH-stimulated GH release can be exerted at sites distal to cAMP production and PKC activation, respectively. SRIF also exerts its effect at sites distal to calcium mobilization. Since SRIF inhibition was more effective against Bay K 8644-induced response than against ionophore-induced GH response, an inhibitory action at the level of extracellular calcium entry through voltage-sensitive channels is also possible.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats.

The purpose of this study was to evaluate the dose-effect relationship of recombinant human PTH [hPTH-(1-84)] and synthetic human PTH [sPTH-(1-34)] for the skeleton of estrogen-deplete osteopenic rats. Ex vivo densitometry of regionalized whole femurs and histomorphometry of proximal tibial cancellous bone were the end points. Retired breeder female rats, aged 6-7 months, were used. Ten were killed at baseline, and the rest were ovariectomized (OVX). On day 42, a pre-PTH treatment OVX group was killed. The rest were then treated by daily sc injection with hPTH (0, 1.55, 15.5, or 155 micrograms/kg BW.day) or sPTH (0.55, 5.5, or 55 micrograms/kg BW.day) and killed on day 70. The level of cancellous bone mineral was lower in pretreatment OVX rats than at baseline. It was higher in rats treated with 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH than in pretreatment and vehicle-treated OVX rats. Cancellous bone volume was also lower both 42 and 70 days after OVX. Although hPTH did not affect cancellous bone volume, treatment with 5.5-55 micrograms/kg.day sPTH caused higher bone volume than in either pretreatment or vehicle-treated OVX rats. Trabecular number declined after OVX and did not change with PTH treatment. In contrast, trabecular thickness declined after OVX, but was higher after 15.5-155 micrograms/kg.day hPTH and 5.5-55 micrograms/kg.day sPTH treatment. In OVX rats, the amount of mineralizing surface was greater by day 42 and fell toward control levels by day 70. It was greater in rats treated with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH than in vehicle-treated OVX rats. On a molar basis, sPTH was modestly more potent than hPTH. Osteoclast surface was not affected by PTH treatment. Treating estrogen-deplete osteopenic adult rats for 28 days with 15.5-155 micrograms/kg.day hPTH or 5.5-55 micrograms/kg.day sPTH increases trabecular thickness, but not trabecular number, to cause a rise in bone mass. The extent of mineralizing surface rises without a change in resorption surface. The marked rise in mineralizing surfaces suggests that extended in vivo treatment with PTH activates osteogenic precursor cells near once quiescent surfaces to become osteoblasts.

Animals↗
PubMed1982

201Tl perfusion study of "ischemic" ulcers of the leg: prognostic ability compared with Doppler ultrasound.

Thallium 201 perfusion analysis was compared with Doppler ultrasound as a means of determining the healing potential of an ischemic ulcer of the leg in 27 patients. The degree of hyperemia was determined by comparative point counting of the 201Tl distribution in and about the ulcer. Using established Doppler criteria and a hyperemia ratio greater than 1.5:1, ultrasound alone correctly predicted healing in 15 out of 23 cases and 201Tl in 20 out of 23. Ultrasound correctly predicted non-healing in 3 out of 6 cases, compared with 5 out of 6 for 201Tl. The positive predictive value of the 201Tl study was 63%, versus 27% for ultrasound, and the negative predictive value was 95% for 201Tl and 83% for ultrasound. The accuracy of 201Tl and ultrasound was 86% and 62%, respectively. This limited study suggests that 201Tl perfusion scanning is a useful noninvasive test of ulcer healing potential and may be more sensitive than Doppler ultrasound.

Adult↗
PubMed1976

Acute carpal tunnel syndrome secondary to pseudogout: case report.

Acute carpal tunnel syndrome secondary to chondrocalcinosis seems not to have been previously reported. In a 75-year-old woman, with arthropathy and calcification of the triangular fibrocartilage of the wrist, hyperparathyroidism was suspected, but not proven. Hydroxyapatite and calcium pyrophosphate crystals were found together in the pathological specimen. The patient obtained complete relief from sectioning of the transverse carpal ligament.

Aged↗