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A R Buckley

Publications and source records attributed to A R Buckley.

At least 73 records · Page 4Linked to original sources
PubMed1991

Prolactin activates protein kinase C and stimulates growth-related gene expression in rat liver.

We have examined the effect of prolactin (PRL) on growth-related gene expression, protein kinase C (PKC) activity and diacylglycerol (DAG) mass in rat liver. Hepatic levels of messenger (m)RNA for c-myc, ornithine decarboxylase (ODC) and beta-actin increased in a dose-dependent manner within 1 h after PRL administration. Prolactin also caused a transient elevation of liver DAG levels and particulate-associated PKC activity. The PRL-provoked increases in DAG mass and particulate PKC activity were coincident and maximal at 20 min and began declining toward control levels by 30 min. These results suggest a temporal relationship between PRL-stimulated DAG accumulation and PKC activation. Furthermore, the subsequent rapid induction of growth-related gene expression provides new information on the role of PRL as a hepatic mitogen.

Actins↗
PubMed1991

Gallbladder contractility: variation in normal subjects.

Gallbladder contractility can be quantified radiologically, but it is not known whether the degree of contraction exhibited by a person's gallbladder varies from day to day. Thirty healthy volunteers were studied with sonography on three separate occasions to determine the variation of individual gallbladder contractility. Using the ellipsoid method, we measured gallbladder volume after an overnight fast (fasting gallbladder volume) and between 45 and 60 min after a standard fatty meal (residual gallbladder volume). Percentage gallbladder contraction was calculated by dividing the difference between the fasting and residual gallbladder volumes by the fasting gallbladder volume and multiplying by 100. The 90 studies in 30 subjects exhibited a wide range of values: fasting gallbladder volume from 1.9 to 45.5 ml, residual gallbladder volume from 0.1 to 21.0 ml, and percentage gallbladder contraction from -10% to 99%. Within each subject, fasting gallbladder volume measurements varied from 1.5 to 26.2 ml (mean +/- two standard deviations, 10.3 +/- 5.1 ml) and residual gallbladder volume from 0.3 to 15.4 ml (5.1 +/- 3.8 ml). Percentage gallbladder contraction varied from 6% to 87% (28% +/- 18%). In 60% of the subjects, percentage gallbladder contraction values varied by more than 20%, and in 20% of the subjects it varied by more than 40%. These data show that a wide variation exists within a normal person in the degree of gallbladder contraction exhibited from one day to another, and a single test for gallbladder contraction can be misleading.

Adult↗
PubMed1990

Prolactin and known modulators of rat splenocytes activate nuclear protein kinase C.

Prolactin (PRL) and other trophic factors rapidly activate a nuclear pool(s) of protein kinase C (nPKC) in purified splenocyte nuclei. The PRL also enhanced [2-3H]glycerol incorporation into nuclear mono- and triacylglycerol. An assay was devised which not only probed the ability of the hormone to activate protein kinase C (PKC) but also demonstrated the presence of nuclear substrates. Using this methodology, a biphasic concentration-response curve to PRL was observed. Heterologous species of PRL and various growth factors also activated nPKC. The PRL-induced nPKC stimulation was antagonized by various immunomodulators, G protein-coupling inhibitors, PKC inhibitors, a calmodulin inhibitor, and a peripheral benzodiazepine agonist and antagonist. A monoclonal antibody to PKC, anti-rat PRL antiserum and a monoclonal anti-rat PRL receptor antibody antagonized PRL-induced PKC-dependent nuclear phosphorylation, further implicating nPKC and a PRL receptor-mediated activation process. Nuclear PKC may be a major target for trophic regulation in response to both positive and negative growth signals.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Fatal carcinoid crisis after percutaneous fine-needle biopsy of hepatic metastasis: case report and literature review.

Immediately after a fine-needle aspiration biopsy (FNAB) was performed of a carcinoid liver metastasis, a patient had severe flushing, nausea, and faintness, followed by generalized seizure activity, profound hypotension, and cardiopulmonary arrest refractory to resuscitative efforts. This was considered due to massive release of vasoactive substances into the systemic circulation, caused by manipulation of the tumor at biopsy and aggravated by resuscitative efforts. Hypotensive crisis should be considered a potential, although unusual, complication of FNAB of liver metastases in patients with carcinoid syndrome. If biopsy is necessary, an intravenous access line should be established before biopsy is performed, and personnel should be prepared to administer emergency resuscitation. Medication with a somatostatin analogue before biopsy is performed is suggested. Catecholamine administration should be avoided.

Biopsy, Needle↗
PubMed1989

Prolactin stimulation of protein kinase C activity in rat aortic smooth muscle.

Prolactin (PRL) activated protein kinase C (PKC) in a dose dependent manner in rat aortic smooth muscle. Aortic strips incubated with sub-nanomolar concentrations of ovine PRL for 25 min. at 37 degrees C showed a significant stimulation of PKC activity in both cytosolic and particulate fractions. This activation could be blocked using either anti-PRL antibodies or 1-(5- isoquinolinesulfonyl)-2-methylpiperazine (H-7), a PKC inhibitor. The results further support the role of PKC in the signal transduction pathway for PRL action and suggest that this activation may be involved in vascular smooth muscle function.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Hypothalamic site of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Administration of TCDD produced a significant decrease in the serum concentration of prolactin (PRL) detected in rats after 4 hr compared to pair-fed vehicle controls and noninjected controls. This effect of TCDD was reversed by pimozide, a dopamine receptor antagonist. These data suggest that TCDD decreased the release of PRL from the adenohypophysis either by a direct effect on the gland or by altering the dopamine concentration in the median eminence (ME). Concentrations of TCDD from 5 to 500 ng/ml had no direct effect on the ability of the adenohypophysis to secrete PRL in vitro. However, the dopamine concentration increased to 3.24 +/- 0.07 ng per ME in TCDD-treated rats compared to 2.81 +/- 0.08 ng in vehicle controls. This is a dramatic alteration in the dopamine concentration, since the dopamine is being measured in the portal circulation which exhibits a rapid turnover. The rate constant of dopamine depletion after alpha-methyl-p-tyrosine and the turnover rate were also significantly elevated in the ME of TCDD-treated rats. These data provide the first biochemical evidence for a hypothalamic site of action of TCDD. Since dopamine is inhibitory to PRL release from the adenohypophysis, increased ME steady-state concentrations and turnover of this catecholamine may be responsible for the decreased concentration of serum PRL detected within 4 hr of TCDD injection. Thus, one of the early modes and sites of action of TCDD is to elevate the dopaminergic activity of the tuberoinfundibular nucleus. A hypothalamic site of action for TCDD may result in a number of the endocrinological effects known to be produced by exposure to TCDD.

Animals↗
PubMed1988

Prolactin as a mammalian mitogen and tumor promoter.

Cellular proliferation and differentiation of the mammalian mammary gland requires a medley of hormones including the anterior pituitary hormone, PRL. Recent evidence extends the role of PRL as a mammalian mitogen to cells in several physiological systems not directly involved in reproductive functions, such as liver and lymphocytes. PRL administration induces biochemical markers expressed during the G1 phase of cell cycle and activates DNA synthesis in rat liver. Chronic PRL treatment causes hepatomegaly, reflecting its stimulation of the proliferative process. In vitro, a lactogen-dependent cell line, the Nb2 rat node lymphoma cell, serves as a useful paradigm to study PRL action on mitogenesis. These cells, when cultured in the presence of lactogens, proliferate in a dose-dependent manner. The effects of various pharmacological agents on discrete phases of the cell cycle may be readily assessed in these cells since PRL-stimulated entry into cycle is signalled by an elevation of ODC activity at 6 hr and entry into S-phase at 6-12 hr. The parallel effects of phorbol ester tumor promoters and PRL on cell cycle progression in Nb2 lymphoma cells and in hepatic proliferation suggest that PRL may likewise mediate proliferation in aberrant growth conditions such as neoplasia. The data presented support the hypothesis that PRL is capable of promoting hepatocarcinogenesis. Its chronic administration after a hepatic initiating agent stimulated the development of histochemical and biochemical markers characteristic of preneoplasia. Further, the effect of PRL was comparable to that of the hepatocarcinogen when either was administered alone. Thus, hyperprolactinemia may serve to promote the development of hepatic tumors. Phorbol esters are thought to promote tumorigenesis by directly activating PKC. In the Nb2 lymphoma cell model, tumor promoting phorbol esters mimic the effects of PRL. Similarly, PRL-stimulated enzyme induction in liver is mirrored by phorbol ester treatment, and inhibitors of PKC block PRL-stimulated mitogenesis in Nb2 cells. Further, PRL or TPA administration to rats causes translocation of PKC activity from the hepatic cytosol to the membrane fraction, reflecting kinase activation. Therefore, PRL activation of PKC appears to be a physiological phenomenon of general significance, occurring as the result of lactogen receptor stimulation and serving to transmit intracellular signals linked to the regulation of mitogenesis. Further study is required to more fully define the scope of PRL-mediated mitogenic actions as well as its effects on the expression of differentiated products in tissues and cells.

Animals↗
PubMed1988

Rapid activation of protein kinase C in isolated rat liver nuclei by prolactin, a known hepatic mitogen.

Rat liver nuclei pure by enzymatic and electron microscope criteria contain protein kinase C (PKC) that can be activated several hundredfold within 3 min of addition of prolactin or phorbol 12-tetradecanoate 13-acetate. Rat prolactin stimulated PKC maximally at 10(-12) M, whereas ovine prolactin was maximally stimulatory at 10(-10) M. Activation was time and dose dependent, exhibited a biphasic pattern, and was blocked by anti-prolactin antiserum, by PKC inhibitors such as 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and sphingosine, and by cyclosporine. Moreover, the ability of prolactin to activate nuclear PKC was inhibited totally by a monoclonal antibody to the rat liver prolactin receptor, implicating a prolactin receptor-mediated activation process. Epidermal growth factor (EGF), a liver mitogen, caused a lesser but significant activation of nuclear PKC. However, EGF and suboptimal prolactin were synergistic. Human growth hormone, which has lactogenic properties, stimulated PKC activity, whereas nonlactogenic substances such as ovine growth hormone, insulin, dexamethasone, and 8-bromo-cAMP were inactive. That this may be a general mechanism for prolactin is suggested by the ability of prolactin to stimulate PKC 140-fold in rat splenocyte nuclei. Prolactin has comitogenic properties in lymphocytes.

Animals↗
PubMed1988

Neuronal migration abnormalities can still be diagnosed by computed tomography!

Magnetic resonance imaging is presently the best modality for evaluating gray/white matter anatomy. However, this modality is expensive and not yet readily available in all countries. Most neuronal migration abnormalities can be accurately diagnosed by computed tomography (CT) provided excellent scanning technique is used. Abnormalities of neuronal migration were identified with CT brain scans in 68 children and were categorized as focal heterotopias (11 patients), multifocal heterotopias (19 patients) of diffuse migration disorders (38 patients). The principal indications for imaging were correlated to the radiological features. Neuropathological confirmation of the migration abnormality was obtained in 8 patients. An increased awareness by both clinicians and radiologists together with optimal CT technique are essential for the accurate diagnosis of migration disorders in children.

Brain↗
PubMed1987

Hepatic protein kinase C: translocation stimulated by prolactin and partial hepatectomy.

Prolactin stimulates a hepatotrophic response similar to that caused by phorbol esters or partial hepatectomy in rats. Since phorbol esters, which activate protein kinase C, mimic prolactin action in liver, the relationship between prolactin administration and subsequent hepatic protein kinase C translocation was assessed. Prolactin administration rapidly stimulated a 4-fold elevation of membrane protein kinase C activity. The effect of prolactin on hepatic protein kinase C was specific for lactogenic hormones but could be duplicated by phorbol esters. Further, an increase in serum prolactin was demonstrated subsequent to partial hepatectomy and preceding hepatic protein kinase C translocation. Therefore, translocation of hepatic protein kinase C appears important for hepatic proliferation in response to prolactin administration and to partial hepatectomy.

Animals↗
PubMed1987

Concanavalin A-stimulated murine splenocytes produce a factor with prolactin-like bioactivity and immunoreactivity.

Culture supernatants from concanavalin A activated murine splenic mononuclear cells (splenocytes) were assayed for prolactin-like molecules using the Nb2 node lymphoma bioassay and immunostaining procedures. Con A stimulated splenocytes produced a factor with prolactin-like immunoreactivity that was mitogenic for Nb2 lymphoma cells. This factor first appeared in culture supernatants with the onset of lymphocyte mitogenesis and its activity was proportional to the number of cells cultured. In addition, splenocyte proliferation was inhibited by antiserum to rat prolactin, and this inhibition was partially reversed by added hormone. These findings show that murine splenocytes produce a substance with prolactin-like activity and suggest that this factor is essential for lymphocyte proliferation.

Animals↗
PubMed1987

Prolactin-dependent mitogenesis in Nb 2 node lymphoma cells: effects of immunosuppressive cyclopeptides.

Prolactin (PRL)-stimulated ornithine decarboxylase (ODC) activity and subsequent proliferation are inhibited by the cyclopeptides cyclosporine (CsA) and didemnin B (DB) in Nb 2 node lymphoma cells. Similar concentrations of these agents also inhibit 125I-PRL binding, suggesting that their inhibitory effects on these PRL-dependent physiologic responses are mediated at least in part at the level of PRL receptor interactions. The phorbol ester TPA stimulated ODC activity and [3H]thymidine incorporation to 54% and 31% that of a near-optimal mitogenic concentration of PRL (10 ng/ml), suggesting that mitogenesis in these cells is coupled to some degree to the activation of protein kinase C (PKC). The calcium ionophore A23187 increased ODC activity only slightly and actually decreased [3H]thymidine incorporation to a value below the "cells only" controls. The addition of TPA plus A23187 did not further enhance the effects of TPA to elevate ODC activity and [3H]thymidine incorporation. However, A23187 significantly elevated PRL-stimulated ODC activity with a subsequent inhibition of [3H]thymidine incorporation, suggesting a block of entry into S phase. Both cyclopeptides decreased the elevation of ODC activity in G1 phase of cell cycle in response to PRL, suggestive of a site of action for these agents in early G1, a conclusion compatible with their ability to inhibit PRL binding to these cells. Addition of CsA or DB 2 hr after PRL had no effect on PRL-stimulated ODC activity detectable at 6 hr, but addition of either as late as 6 hr still affected the extent of mitogenesis. This is in line with the requirement for PRL to be present in the culture medium for a minimum of 3 to 6 hr to invoke a maximal effect on mitogenesis. Addition of either cyclopeptide after the cells were in S phase had no effect on the extent of [3H]thymidine incorporation. An inhibitor of the cyclooxygenase pathway (indomethacin) enhanced both PRL-stimulated ODC activity and proliferation, whereas inhibition of the lipoxygenase pathway by NDGA attenuated only proliferation, suggesting that in Nb 2 cells, products of the lipoxygenase pathway may contribute to the mechanism of PRL-stimulated mitogenesis. Because Nb 2 lymphoma cells were derived from estrogenized rats, estrogen was tested as a mitogen. By itself it was not mitogenic, but in conjunction with PRL, estradiol-17 beta elevated the ODC response and inhibited proliferation. Inhibitors of PKC known to have minimal effects on RNA synthesis, quercetin and gossypol, totally inhibited both the elevations of ODC activity and [3H]thymidine incorporation in response to PRL in Nb 2 lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗