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Biomedical subjects

K D Jones

Publications and source records attributed to K D Jones.

At least 55 records · Page 3Linked to original sources
PubMed1991

The role of lactic acid in autocrine B-cell growth stimulation.

Growth and survival of Epstein-Barr virus (EBV)-immortalized B lymphocytes cultured at low cell densities require autocrine soluble factors. In this study, we have purified a low molecular weight autocrine soluble factor that promotes growth of EBV-immortalized B cells in serum-free conditions and identified it as lactic acid (LA). Synthetic LA stimulated growth in EBV-immortalized B cells at 1-10 mM, a concentration of LA measured in the culture supernatant of EBV-immortalized cell lines. LA alone was found to account for greater than 70% of the autocrine growth factor activity in serum-free supernatants of EBV-immortalized B cells. Aminooxyacetate, a glutamate-oxaloacetate transaminase inhibitor, specifically inhibited B-cell growth induced by LA, suggesting that this process requires mitochondrial-cytosol transfers. Thus, LA is an autocrine stimulatory molecule that in serum-free conditions is essential for the continuous proliferation of EBV-immortalized B cells. This represents an unexpected function for LA.

Animals↗
PubMed1990

Interleukin-1 induces interleukin-6 production in peripheral blood monocytes.

Interleukin-6 (IL-6), a multifunctional cytokine produced in monocytes, fibroblasts, endothelial cells, and keratinocytes, is induced by a variety of stimulating signals, including lipopolysaccharide (LPS), poly (I), poly (C), IL-1, tumor necrosis factor (TNF), and platelet-derived growth factor. Some of these signals induce IL-6 effectively only in one cell type, and this selectivity of induction may explain selectivity of biologic effects. In the present study, we show that IL-1 beta, previously known to be a potent inducer of IL-6 in fibroblasts, endothelial cells, and keratinocytes, but not in monocytes, is also a potent inducer of IL-6 in peripheral blood monocytes. High level IL-6 activity that could be neutralized by specific antibodies to IL-6 was detected in supernatants of IL-1-stimulated monocytes. Maximal induction required IL-1 concentrations of 10 ng/mL. As judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, IL-6 species of relative molecular mass of 19 to 26 Kd could be specifically immunoprecipitated from supernatants of IL-1-induced monocytes. Size heterogeneity is a reported feature of IL-6 produced in a variety of cell types, and monocyte-derived IL-6 induced by either IL-1 or LPS displayed similar size heterogeneity. The highly purified recombinant IL-1 beta preparation used contained little, if any, LPS. In addition, monocyte production of IL-6, induced by IL-1 beta, was specifically neutralized by anti-IL-1 beta antibodies, demonstrating that IL-1, rather than a contaminant in the IL-1 preparation, was responsible for IL-6 induction. A number of biologic activities have been ascribed both to IL-1 and IL-6. The finding that IL-1 induced IL-6 in monocytes may help in defining the spectrum of biologic activities of each of these interactive cytokines.

Cells, Cultured↗
PubMed1990

Identification of interleukin-6 as an autocrine growth factor for Epstein-Barr virus-immortalized B cells.

Autocrine growth factors are believed to be important for maintenance of an immortalized state by Epstein-Barr virus (EBV), because cell-free supernatants of EBV-immortalized cell lines promote the proliferation of autologous cells and permit their growth at low cell density. In this study, we provide evidence for the existence of two autocrine growth factor activities produced by EBV-immortalized lines distinguished by size and biological activities. Much of the autocrine growth factor activity in lymphoblastoid cell line supernatants resided in a low-molecular-weight (less than 5,000) fraction. However, up to 20 to 30% of the autocrine growth factor activity resided in the high-molecular-weight (greater than 5,000) fraction. While the nature of the low-molecular-weight growth factor activity remains undefined, the high-molecular-weight growth factor activity was identified as interleukin-6 (IL-6). Culture supernatants from six EBV-induced lymphoblastoid cell lines tested contained IL-6 activity, because they promoted proliferation in the IL-6-dependent hybridoma cell line B9. In addition, a rabbit antibody to human IL-6 neutralized the capacity of the high-molecular-weight (greater than 5,000) fraction of a lymphoblastoid cell line supernatant to promote growth both in autologous EBV-immortalized cells and in B9 cells. Similarly, this high-molecular-weight autocrine growth factor activity was neutralized by a monoclonal antibody to human IL-6. Furthermore, characteristic bands, attributable to IL-6, were visualized in supernatants of each of four EBV-induced lymphoblastoid cell lines after immunoprecipitation with a rabbit antiserum to human IL-6. Thus, in addition to its previously reported properties, IL-6 is an autocrine growth factor for EBV-immortalized B cells cultured under serum-free conditions.

B-Lymphocytes↗
PubMed1988

Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6).

Soluble products of either Epstein-Barr virus (EBV)-infected B cells or activated monocytes promote the proliferation of EBV-infected B cells and permit their growth at low cell densities. This suggests that growth factors are important for B-cell immortalization by EBV. In this study, a monocyte-derived factor that promotes the growth of EBV-infected b cells was purified and identified as interferon-beta 2 (IFN-beta 2), which is also known as 26-kilodalton protein, B-cell differentiation factor (BSF-2), and interleukin-6 (IL-6). The purified protein has a specific activity of approximately 4 X 10(7) units per milligram of protein in assays of B-cell growth. Thus, IFN-beta 2/BSF-2 is a B-cell growth factor that promotes the proliferation of human B cells infected with EBV.

B-Lymphocytes↗
PubMed1988

Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs.

Haloperidol exhibits a high affinity for a subclass of sigma- "opiate" binding sites which have a unique anatomic distribution and a unique drug selectivity pattern. These binding sites differ from phencyclidine-sensitive sigma-receptors and are found in many brain areas involved in the control of movement. 1,3-Di-o-tolylguanidine (DTG), a highly selective ligand for the haloperidol-sensitive sigma-receptor, produced marked dystonia in rats after microinjection into the red nucleus, a motor area rich in this receptor. Haloperidol and another sigma-ligand [(+)-SKF 10,047] produced similar effects. On the other hand, clozapine, an antipsychotic drug which fails to bind to sigma-receptors and fails to induce movement disorders in humans, failed to induce these dystonic reactions in rats. Phencyclidine was also without effect, as were injections of the active compounds in sites distant to the red nucleus. Microinjections of DTG in the substantia nigra produced vigorous contralateral circling behavior at extremely low doses. These findings suggest that sigma-binding sites represent biologically functional receptors that are active in the neural control of movement. Since haloperidol (and many other antipsychotic drugs) exhibit an affinity for sigma-receptors which is at least equal to its affinity for dopamine receptors, these data raise the further possibility that sigma-receptors are involved in the motor side effects of antipsychotic drugs.

Animals↗
PubMed1987

Proteolysis of human C-reactive protein produces peptides with potent immunomodulating activity.

We have studied the ability of human C-reactive protein to modulate the immune response in vitro. Whereas native C-reactive protein did not induce phagocytic leukocytes to chemotax or to produce superoxide, treatment of purified C-reactive protein with human neutrophil-derived acid proteases produced substances with potent effects on leukocyte function. Close examination of the primary structure of human C-reactive protein revealed three regions evenly distributed throughout the protein each of which contain peptide sequences closely resembling the amino acid sequence of the immunomodulator peptide tuftsin, Thr-Lys-Pro-Arg. We have synthesized the three peptides which include Thr-Lys-Pro-Leu ([Leu4]tuftsin), Gly-Lys-Pro-Arg ([Gly1]tuftsin), and Thr-Lys-Pro-Gln ([Gln4]tuftsin) and assayed them for biological activity. The three synthetic peptides were found to stimulate phagocytic leukocytes to chemotax, produce superoxide, and induce mononuclear cells to produce interleukin 1 in vitro at concentrations similar to those concentrations required for tuftsin to induce these phenomena. These results support a potentially important role for C-reactive protein as a possible immunomodulator during inflammation.

Amino Acid Sequence↗
PubMed1985

C-reactive protein mediates the solubilization of nuclear DNA by complement in vitro.

We have studied the interaction of C-reactive protein (CRP)-chromatin complexes with serum. The amount of chromatin solubilized by serum is directly proportional to the amount of CRP present. Serum minus C3 did not appreciably solubilize chromatin within the time allowed in these experiments regardless of the amount of CRP present. This indicates that, in addition to CRP, complement is critical to the solubilization process. Studies using genetically C2-deficient serum and purified C2 indicate that the classical complement pathway is primarily involved in the solubilization, however, there may be minor involvement by the alternative pathway. We used an enzyme-linked immunosorbent assay to determine the amounts of CRP in plasma from eight patients with systemic lupus erythematosus; two of the eight had levels of CRP far lower than previously reported for normal individuals, and an additional sample had antibodies reactive with CRP. Together, these results suggest that one of the functions of CRP is to mediate the removal of exposed nuclear DNA by complement-dependent solubilization of chromatin. A defect in this mechanism could (a) facilitate the production of antibodies against chromatin components exposed due to tissue damage or (b) contribute to immune complexes containing the chromatin components released from damaged tissue because they are not rapidly cleared.

C-Reactive Protein↗
PubMed1984

Binding of C-reactive protein to chromatin and nucleosome core particles. A possible physiological role of C-reactive protein.

By using a variety of biochemical techniques, chromatin and chromatin fragments have been identified as probable physiological ligands for C-reactive protein. Studies using 14C-labeled C-reactive protein show that binding to chromatin is saturable with a Kd = 8 X 10(-7) M, a value indicating that the affinity of C-reactive protein for chromatin is at least four times its affinity for phosphorylcholine. At saturation, there is approximately one C-reactive protein-binding site for every 160 base pairs of DNA in chromatin. The interaction of C-reactive protein with chicken erythrocyte nucleosome core particle has been studied. Fifty per cent inhibition of the binding of C-reactive protein to phosphorylcholine is obtained at a core particle concentration of 1.25 X 10(-9) M, indicating that the affinity of C-reactive protein for one of the sites on core particles is at least 2400 times greater than the affinity of C-reactive protein for phosphorylcholine. The possibility that C-reactive protein may act as a scavenger for chromatin fragments released from damaged cells is discussed.

Animals↗
PubMed1979

Vision health education: an idea whose time has come.

Health education has been a cornerstone of public health activities for over one hundred years, but recently it has received renewed interest as a method of promoting preventive health care and individual responsibility for one's own health status. While vision health education has not received the attention that other areas of health education have, the need for such information is apparent, and its anticipated effect upon the visual welfare of the population should be obvious. This paper accentuates some of the common objectives of doctors of optometry and health education specialists.

Delivery of Health Care↗
PubMedDate not supplied

Selecting doctoral programs in nursing: resources for students and faculty.

Sixty-nine doctoral programs in nursing are currently offered at 75 universities in the United States. Resources to assist prospective doctoral students in making decisions concerning successfully pursuing doctoral education are collected and organized by a variety of nursing organizations. Nurses in academic settings access these lists and specialty publications through their deans' offices and professional affiliations. Prospective students, on the other hand, are largely employed in clinical settings and are often unaware of the existence of this information, which could assist them in their decisions. The purpose of this article is to provide prospective doctoral students and the faculty that may advise them with a current information to use in selecting a doctoral program in nursing.

Education, Nursing, Graduate↗
PubMedDate not supplied

Dyspareunia: three case reports.

Dyspareunia, a symptom rather than a diagnosis, is defined as pain experienced by a woman during intercourse. This article discusses how to elicit an accurate sexual history and lists 12 common causes of dyspareunia. Three case reports from the authors' practices will be used to describe the diagnosis and treatment of women with vulvar vestibulitis, hymenal strands, and vaginismus.

Adult↗
PubMedDate not supplied

Long-term follow-up of a controlled trial of laser laparoscopy for pelvic pain.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the long-term efficacy of laparoscopic laser surgery in the treatment of painful pelvic endometriosis. METHODS: We conducted a long-term follow-up of 56 patients who had participated in a randomized, double-blind controlled study at a tertiary referral center for the laparoscopic treatment of endometriosis. The patients had pelvic pain, minimal-to-moderate endometriosis, and underwent laser laparoscopy. We asked patients whether they had now achieved satisfactory symptom relief or whether they had received any further medical intervention for their endometriosis. The main outcome measure was continued symptom relief after treatment and subsequent medical history. RESULTS: Of the original 56 patients, we were able to contact 38 (67.9%). The mean (range) time since operation was 73 months. Painful symptoms had recurred in 28/38 (73.7%) patients at some point since their operation. The median (range) time for recurrence was 19.7 (5-60) months. At the time of follow-up, satisfactory symptom relief was reported in 21/38 (55.3%) patients. The remaining 17/38 (44.7%) patients continued to experience painful symptoms, and eight eventually had a hysterectomy. CONCLUSIONS: This study suggests that operative laparoscopy can have long-term benefits for the majority of women with pelvic pain due to endometriosis, but because of the small numbers, this study lacks the power to demonstrate this conclusively.

Adolescent↗