Search PubMed⌕ Search

Biomedical subjects

D H Russell

Publications and source records attributed to D H Russell.

At least 91 records · Page 5Linked to original sources
PubMed1988

Neonatal administration of prolactin antiserum alters the developmental pattern of T- and B-lymphocytes in the thymus and spleen of BALB/c female mice.

We have evaluated the effect of neonatal administration of mouse prolactin (PRL) antiserum on the developmental expression of T- and B-lymphocytes in the thymus and spleen of female BALB/c mice. Newborn female mice were injected subcutaneously with a 50-microliters aliquot of PRL antiserum or normal rabbit serum on days 1, 2, and 3. On neonatal day 5, the PRL antiserum-treated group had a significantly (P less than 0.05) increased population of cells in the thymus and the spleen that were positive for Thy-1.2 and for L3T4. Increases in Thy-1.2- and L3T4-positive cells in the thymus were detectable also on days 8 and 14 in mice that received the PRL antiserum and in mice injected with bromocriptine, a dopamine agonist that inhibits PRL release from the anterior pituitary. On neonatal days 21, 28, and 32, there were no significant differences in the percentage of cells positive for Thy-1.2, Ly-2 (formerly Lyt-2), or L3T4 antigens in the thymus. However, there were significant increases in the percentage of Thy-1.2- and L3T4-positive spleen cells in the bromocriptine-treated group at all times monitored and in the PRL antiserum-treated group except on day 14. In addition, the percentage of splenocytes that were positive for IgG was significantly increased in the PRL antiserum-treatment group on days 8-28, although not on neonatal day 32. Of tissues known to contain PRL receptors, neonatal administration of PRL antiserum or bromocriptine resulted in a significant alteration in the wet weight of spleen and liver, with no significant effect in thymus, heart, and kidney. Pituitary implants also resulted in a significant increase in both concanavalin A- and lipopolysaccharide-stimulated thymidine incorporation into murine splenic lymphocytes prepared from 45-day-old female mice. These data extend the role of PRL as an immunomodulator of adult lymphocyte function to a role in the developmental expression of T- and B-lymphocyte populations in the thymus and spleen of mice.

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

Biological and immunological characterization of cleaved and 16K forms of rat prolactin.

A cleaved form of rat PRL (rPRL) has been reported to exist in the pituitary gland and to be the main product of PRL proteolysis by its target tissues. A 16K fragment derived from cleaved PRL (cPRL) has mammary mitogenic activity in rats in vivo, and we found that both cleaved and 16K PRLs are capable of binding to hepatic PRL receptors. To analyze the functional significance of cleaved and 16K PRLs, ample amounts of cPRL were generated by incubation of 24K rPRL in vitro with a 25,000 X g rat mammary gland pellet. cPRL was reduced (2-mercaptoethanol), and the 16K and 8K fragments were separated by gel filtration. The purity of the cleaved and 16K samples was established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their mitogenic [pigeon crop-sac, Nb2 lymphoma cell, and mammary cell bioassays (BAs)], lactogenic (casein BA), and immunologic (PRL RIA) activities were determined. cPRL had the same mitogenic activity, but half the immunoactivity, as intact PRL. The 16K fragment was biologically active in all assays. Its estimated mitogenic and lactogenic potencies were 65% and 10% those of the 24K PRL, respectively, and it had only 2% the immunoactivity of the intact hormone. Thus, the 16K fragment had higher BA to RIA ratios than cleaved or intact 24K PRLs. The functional significance of 16K PRL may have been underestimated owing to its low RIA activity.

Animals↗
PubMed1988

Urinary polyamines as markers of cardiac allograft rejection. A clinical evaluation.

Histologic evaluation of endomyocardial biopsy specimens is the current method of monitoring rejection after cardiac transplantation. Unfortunately, this technique gives a discontinuous evaluation of the recipient immunologic status. A noninvasive marker of immunologic activation and of allograft rejection that would permit a more continuous monitoring than the biopsy technique would be clinically useful. Urinary polyamine excretion reflects cellular proliferation or degeneration and, as a marker of cellular metabolic activity, may also reflect lymphocyte proliferation and organ rejection. From July 1985 to December 1986, urinary polyamines were studied in 18 patients during hospitalization for heart and heart-lung transplantation. Endomyocardial biopsy was performed twice a week and histologic rejection was characterized by standard criteria. Urinary specimens were collected daily and analyzed for polyamines by high-pressure liquid chromatography. Concentrations of acetylputrescine and total urinary polyamines were significantly higher before the 20 rejection episodes than before the 80 biopsies yielding negative results. So that their clinical usefulness could be evaluated, an elevation of polyamines and a daily level variability of 28% or more was chosen to indicate increased metabolic cellular activity and to predict rejection in the next 8 days. On the basis of these definitions, the sensitivity of polyamine assays to predict rejection was 85%, the specificity 88%, and the positive predictive value 79%. Therefore, serial measurements of urinary polyamines may provide daily information on the recipient's immunologic status after cardiac transplantation.

Adult↗
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↗
PubMed1987

Circadian alterations in prolactin, corticosterone, and thyroid hormone levels and down-regulation of prolactin receptor activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Studies were initiated to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects circadian rhythms of serum prolactin (PRL), corticosterone, thyroxine (T4), and triiodothyronine (T3) in male Sprague-Dawley rats. In addition, the effects of TCDD on PRL receptor activity, as assessed by the ability of PRL to induce ornithine decarboxylase (ODC), were determined. The earliest effect detected following TCDD administration was a significant decrease in the serum PRL concentration compared with that of pair-fed controls within 4 hr (p less than 0.05). This was followed by a significant decrease in serum T4 by 6 hr (p less than 0.05). By 8 hr the serum peak of corticosterone was shifted to 2 hr later in the TCDD-treated rats. This temporal sequence of hormonal changes suggests that the earlier alteration in PRL may be involved in the later alterations in the concentrations of serum T4 and corticosterone. The serum PRL concentration 7 days after TCDD administration was significantly higher (p less than 0.05) in TCDD-treated animals compared with that in pair-fed controls (mean of 20.5 +/- 3.7 vs 13.6 +/- 1.8 ng/ml serum, p less than 0.05, respectively). The elevation of ODC activity in response to PRL, 2 days after TCDD, was decreased in the order of thymus greater than adrenal greater than spleen greater than heart greater than kidney greater than liver. By 7 days, liver ODC activity in response to PRL was only 12% that detected in pair-fed controls. Liver ODC activity in response to dexamethasone and aminophylline was decreased to 25 and 22% of pair-fed controls, respectively, by 7 days after TCDD administration. However, in kidney, TCDD-treated rats had an increased ODC response to aminophylline to 191% of pair-fed controls by Day 7. These results suggest that the ability of TCDD to alter receptor coupling or the receptor number for diverse hormones may play a role in TCDD toxicity.

Aminophylline↗
PubMed1986

Prolactin administration stimulates rat hepatic DNA synthesis.

Prolactin is an important growth modulatory hormone in fetal and adult tissues. Its administration stimulates enzymatic markers of the G1 phase of cell cycle in rat liver and other tissues. To determine the effects of prolactin administration on hepatic DNA synthesis (S phase), rats received prolactin at 12 hour intervals for 48 hours and DNA synthesis was assessed by [3H]-thymidine incorporation. Prolactin administration stimulated DNA synthesis 2-4 fold above controls in the livers of adult and weanling animals. Increased incorporation of radiolabel was associated with the nucleus of hepatoparenchymal cells. These data support the hypothesis that prolactin may be a physiological regulator of hepatic DNA synthesis. Further, since stress stimulates prolactin secretion, we suggest that prolactin may participate in the hepatic compensatory hyperplasia elicited by the stress associated with partial hepatectomy.

Age Factors↗
PubMed1986

Prolactin stimulation of ornithine decarboxylase and mitogenesis in Nb2 node lymphoma cells: the role of protein kinase C and calcium mobilization.

The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with calcium ionophores has been shown to bypass the requisite antigen- or lectin-induced signal for lymphocyte mitogenesis. This suggests that protein kinase C activation and calcium mobilization may be early events required for lymphocyte proliferation. Therefore, the relationship(s) of protein kinase C activation and calcium mobilization to ornithine decarboxylase induction and cellular proliferation were examined in a rat node lymphoma cell line (Nb2) which is dependent upon prolactin (PRL) for mitogenesis. TPA enhanced PRL-stimulated Nb2 node lymphoma cell ornithine decarboxylase induction and [3H]thymidine incorporation. Addition of a calcium ionophore (A23187) to cultures containing TPA plus PRL increased ornithine decarboxylase above PRL alone or PRL plus TPA but inhibited proliferation compared to the PRL plus TPA regimen. Exposure of cells to TPA or TPA plus A23187 increased [3H]thymidine incorporation in a similar manner to that demonstrated for low-dose PRL. However, optimal concentrations were only 20-25% as effective as mitogens as was optimal PRL. Protein kinase C and calmodulin antagonists inhibited PRL-stimulated ornithine decarboxylase induction and proliferation. Ca2+ chelation or cation channel antagonism inhibited both PRL-stimulated responses. The cyclic AMP analogue, 8Br-cAMP, inhibited PRL-stimulated ornithine decarboxylase activity as well as cellular proliferation processes assessed by [3H]thymidine incorporation. Finally, tumor-promoting phorbol esters inhibited 125I-rPRL binding. These data strongly suggest that protein kinase C activation and calcium mobilization are requisite events for PRL-stimulated ornithine decarboxylase induction and cellular proliferation in Nb2 node lymphoma cells. An additional component that is linked to alterations in K+ channeling is also implicated. These data support a role for protein kinase C in PRL-coupled mitogenesis. However, other critical Ca2+ and/or ion-induced events are also required.

Animals↗