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Biomedical subjects

D H Russell

Publications and source records attributed to D H Russell.

At least 73 records · Page 4Linked to original sources
PubMed1990

Adenosine activation of a nuclear pool of protein kinase C in rat splenocytes.

The stimulatory effects of adenosine analogues on a nuclear pool of protein kinase C (PKC) were examined using isolated rat splenocyte nuclei. Nuclear receptors met pharmacological criteria of A1 adenosine receptors including a potency profile in which cyclopentyladenosine (CPA), a selective A1 agonist, was more potent than 2-phenylaminoadenosine (2PAA), a selective A2 agonist. The selective A1 receptor agonist N6-1-(phenyl-2R-propyl) adenosine (R-PIA) activated PKC whereas the S diastereomer did not. The adenosine-induced PKC response could be attenuated using a monoclonal antibody to PKC, an A1 receptor antagonist, three known PKC inhibitors and pertussis toxin (PTX). The results suggest that adenosine may exert immunomodulatory effects through the activation of nuclear PKC.

Adenosine↗
PubMed1990

Regulation of interleukin 2-driven T-lymphocyte proliferation by prolactin.

The requirement for prolactin in interleukin 2-driven T-cell proliferation was evaluated. Addition of an anti-prolactin antiserum resulted in the specific inhibition of T-cell proliferation in a time- and dose-dependent manner. Synthesis of prolactin and its mRNA, however, did not occur during interleukin 2 stimulation. Instead, previously internalized prolactin, presumably from fetal bovine serum, appears to serve as the source of prolactin under serum-free conditions. A 7-fold increase in a prolactin receptor occurred as a function of cell cycle progression; accumulation of a 1.6-kilobase prolactin receptor mRNA increased approximately 2-fold. Interleukin 2 stimulation induced the translocation of prolactin into the nucleus and prolactin receptor to the nuclear periphery. These data indicate that extracellular prolactin is requisite for T-cell proliferation and suggest that the effects of prolactin are exerted in the nucleus.

Animals↗
PubMed1989

Peripheral benzodiazepine binding sites in Nb 2 node lymphoma cells: effects on prolactin-stimulated proliferation and ornithine decarboxylase activity.

[3H]Ro 5-4864 binds to Nb 2 node lymphoma cells in a specific saturable and reversible fashion. Scatchard analysis of specific binding data reveals a single, homogeneous class of whole cell binding sites with a Kd of 3.94 +/- 0.22 nM and a Bmax value of 155 +/- 11 fmol (Ro 5-4864 bound)/2 x 10(6) cells. Ro 5-4864, a reported peripheral benzodiazepine receptor agonist both inhibits (10(-6) M) and potentiates (10(-9) M) the mitogenic action of prolactin on the Nb 2 node lymphoma cells. Interestingly, PK 11195, an antagonist, potentiates (10(-9) M) the mitogenic activity of prolactin in these cells. The actions of both Ro 5-4864 and PK 11195 seem to be mediated through a common receptor type since a 10(-6) M concentration of either agent will block the others potentiating action. Furthermore, the simultaneous addition of a 10(-9) M concentration of Ro 5-4864 and PK 11195 does not further increase the effect on prolactin stimulated mitogenesis. Clonazepam, a central benzodiazepine receptor agonist has no effect on prolactin-stimulated mitogenesis in this system. These data suggest that the Nb 2 node lymphoma cells possess a peripheral-type benzodiazepine receptor. In these cells, this receptor seems to serve the function of modulating the ability of the growth factor, prolactin to initiate the mitogenic process. These studies also suggest that Ro 5-4864 is functioning as a partial agonist rather than a 'pure' agonist for the peripheral benzodiazepine receptor in this system.

Benzodiazepinones↗
PubMed1989

Ion detection by Fourier transform ion cyclotron resonance: the effect of initial radial velocity on the coherent ion packet.

Ion detection by Fourier transform ion cyclotron resonance (FT-ICR) is accomplished by observing a coherent ion packet produced from an initially random ensemble of ions. The coherent packet is formed by excitation with a resonant oscillating electric field. Ions that are out of phase with the applied radio frequency (rf) electric field experience a continuous misalignment of the electric field vector. The misalignment creates a net force of the electric field perpendicular to ion motion. The perpendicular component of the rf electric field creates a frequency shift resulting in phase synchronization of the ion ensemble. The phase coherence of the ion packet affects both the sensitivity and the resolution of FT-ICR.

Electromagnetic Fields↗
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↗
PubMed1989

New aspects of prolactin and immunity: a lymphocyte-derived prolactin-like product and nuclear protein kinase C activation.

In addition to its growth regulating properties, new evidence reviewed here by Diane Haddock Russell demonstrates that prolactin has important immunoregulatory properties. In immune-compromised dwarf mice, prolactin restores immunocompetence. Human lymphocytes have prolactin receptors and mitogen-stimulated lymphocytes make and secrete a prolactin-like activity. Prolactin can stimulate the activation of nuclear protein kinase C in spleen and liver isolated nuclear preparations. This activation is blocked by prolactin receptor monoclonal antibody, suggesting that there is a receptor-mediated activation process in the nucleus. The discovery of the ability of prolactin and growth factors to activate nuclear protein kinase C may constitute a breakthrough in our understanding of how these hormones regulate trophic responses.

Cell Nucleus↗
PubMed1989

Enhancement of prolactin (PRL)-stimulated mitogenesis of Nb2 rat lymphoma cell cultures by insulin-like growth factor I (IGF-I).

IGF-I stimulated the mitogenesis of Nb2 cells in the presence of suboptimal mitogenic concentrations of prolactin (PRL, 0.01 or 0.1 ng/ml). In the presence of 1 ng/ml or 10 ng/ml, concentrations of PRL that produced a maximal or near maximal mitogenic response in Nb2 cells, the addition of insulin-like growth factor-I (IGF-I) at 5 or 10 ng/ml did not further enhance mitogenesis. This effect was selective for IGF-I since IGF-II, epidermal growth factor (EGF), insulin, transforming growth factor-beta (TGF-beta) or platelet-derived growth factor (PDGF) did not stimulate mitogenesis in the presence or absence of PRL. That the ability of IGF-I to stimulate mitogenesis of these cells required PRL was suggested by the ability of PRL antiserum to block the IGF-I effect. Monoclonal antibody to IGF-I reduced the mitogenic response to one identical to PRL alone. In the presence of a suboptimal mitogenic concentration of PRL, IGF-I was an equally effective comitogen when added at 0 time or at 6 h after PRL stimulation, suggestive of an effect of IGF-I in late G1 phase of the cell cycle. Effects of IGF-I on ornithine decarboxylase, a G1 enzymatic marker, were compatible with this interpretation. In order to be assured that IGF-I exerted its action through a receptor-mediated process, we evaluated the presence of IGF-I receptors on Nb2 cells. Receptors were present which bound IGF-I greater than IGF-II much greater than insulin. The IC50 was 35 nM for IGF-I, 280 nM for IGF-II and 875 nM for insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Structural and functional alterations in the zona fasciculata of the rat adrenal cortex in obstructive jaundice.

This study investigated the effect of experimentally-induced cholestasis in the rat on the structure and function of the zona fasciculata, the glucocorticoid secretory region of the adrenal cortex. Wistar-Furth rats (200-250g) were assigned to three groups: bile duct ligated (BDL), Sham operated (Sham) and unmodified normal control (NC). On day 14, serum bilirubin and liver histology were performed to confirm cholestasis in BDL animals together with basal 24 hour 17-hydroxycorti-costeroid excretion, adrenal histology and zona fasciculata ultrastructure in all experimental groups. Following this laparotomy, structural and functional studies were repeated on day 15 to evaluate the response of the gland to surgically induced stress. Basal 24 hr, 17-hydroxycorticoid steroid excretion was elevated in BDL animals (26.9 +/- 3.2 micrograms/24 hr) with respect to Sham (10.4 +/- 2.3) and NC groups (13.5 +/- 3.2) (p less than 0.05). Adrenal histology and ultrastructural studies demonstrated excessive accumulation of vesicles laden with glucocorticoid biogenic precursors. Following surgical stress 24 hr 17 OH corticosteroid excretion increased in all groups: BDL (31.0 +/- 3.0 micrograms/24 hr) vs Sham (15.6 +/- 1.8) and NC (14.5 +/- 2.4) Moderate alterations in zona fasciculata architecture were seen following surgery in all groups. Cholestasis induces overactivity of the zona fasciculata of the adrenal cortex, and may modify the normal metabolic responses to surgical and other stresses.

17-Hydroxycorticosteroids↗
PubMed1989

Solubilization and characterization of the liver peripheral-type benzodiazepine receptor.

The rat liver membrane-bound and digitonin-solubilized peripheral-type benzodiazepine receptors (mPBZR and dsPBZR, respectively) were characterized. Forty percent of the receptors were solubilized from a liver homogenate with 0.25% digitonin. Scatchard analysis of saturation data for the mPBZR and the dsPBZR showed Kd = 1.5 nM and maximum number of binding sites = 3.12 pmol/mg of protein and Kd = 9.2 nM and maximum number of binding sites = 1.10 pmol/mg of protein, respectively. Estimates of Kd calculated from kinetic data agree with estimates from Scatchard analysis. The affinity of the PBZR for [3H]Ro5-4864 was not affected by guanosine 5'0-(3-thiotriphosphate) which suggests the receptor is not coupled to a G-protein. Competition for specific [3H]Ro5-4864 binding by various ligands demonstrated the same rank order potency of binding inhibition for the membrane bound and solubilized receptors (PK-11195 greater than or equal to Ro5-4864 greater than diazepam greater than clonazepam). Thus, the soluble receptor had ligand binding characteristics similar to those of the membrane PBZR. [3H]PK-14105 was used to photoaffinity label the PBZR in a rat liver homogenate. Labeling was specific for the PBZR and the molecular weight of the digitonin-solubilized photoaffinity-labeled receptor was estimated to be 170 kDa by gel filtration chromatography. Estimation of the molecular weight of the [3H]PK-14105 labeled receptor by sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated a single protein corresponding to 19 kDa.

Animals↗
PubMed1988

Mass spectrometry.

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Mass Spectrometry↗
PubMed1988

Bone marrow derived macrophages have polyamine and ectoenzyme phenotypes distinct from resident macrophages.

Several prototype macrophage (MO) populations were compared for differences in ectoenzyme phenotype and polyamine content. Resident peritoneal MO and Corynebacterium parvum (CP)-activated peritoneal MO expressed unique ectoenzyme phenotypes, while bone marrow derived MO (BMDMO), obtained from stem cells after 7 days in culture with colony stimulating factor, and thioglycollate (TG)-elicited peritoneal MO exhibited a similar ectoenzyme phenotype. All of the MO populations, however, differed in polyamine accumulation patterns. These results suggest that ectoenzyme phenotypes do not serve as completely selective markers of MO differentiation. Moreover, BMDMO do not resemble steady state tissue peritoneal MO but appear to resemble inflammatory MO in several respects. Therefore activated BMDMO do not appear to provide an accurate model system for their continued use in studies to characterize the development of resident tissue MO.

5'-Nucleotidase↗
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

Value of urinary polyamines as noninvasive markers of cardiac allograft rejection in the dog.

A noninvasive marker of cardiac allograft rejection would be useful clinically. Lymphocyte proliferation and organ rejection may cause changes in urinary polyamine excretion. To test this hypothesis, cervical heterotopic heart transplantations were performed in a group of 6 nonimmunosuppressed dogs and in a group of 9 dogs treated with cyclosporine (N = 3) or cyclosporine and steroids (N = 6). A group (N = 3) having a sham operation was also studied. Serial biopsies of the transplanted hearts were performed. Urinary polyamine levels were measured daily by high-pressure liquid chromatography of urine specimens. Between 2 and 4 days after transplantation, the transplanted hearts of all animals without immunosuppression demonstrated histological rejection. An early increase in putrescine levels and in total urinary polyamine levels was observed in this group. In the treated groups, histological rejection appeared from the second to the eighth day after transplantation. Each episode of rejection occurred from 1 day to 4 days after a significant increase in urinary polyamine levels compared with the preoperative baseline level (p less than 0.01). In contrast, polyamine excretion in 3 dogs after sham operations remained unchanged. Thus, urinary excretion of polyamines increases before the appearance of histological rejection; this suggests that changes in urinary polyamine levels may be a useful marker of cardiac allograft rejection.

Animals↗