Search PubMed⌕ Search

Biomedical subjects

J D Watson

Publications and source records attributed to J D Watson.

At least 199 records · Page 11Linked to original sources
PubMed1987

Development of fetal thymocytes in organ cultures. Effect of interleukin 2.

Most fetal thymocytes from 14-d mouse embryos are Thy-1+, L3T4-, Ly-2-, and express the receptor for interleukin 2 (IL-2). The development of thymocytes has been followed in fetal thymus organ cultures. When fetal thymus from 14-d embryos were cultured for a 6-d period, thymocytes increased in number 20-40-fold, and 95% became Thy-1+, L3T4+, Ly-2+. The addition of IL-2 to organ cultures of 14-d fetal thymus inhibited, in a dose-dependent manner, cell proliferation and the appearance of Thy-1+, L3T4+, Ly-2+ thymocytes. The addition of IL-2 also resulted in the appearance of a population of cells that were cytotoxic for syngeneic and allogeneic fetal thymocytes and syngeneic tumour targets. While the events that lead to the expression of the IL-2 receptor on 14-d fetal thymocytes are unknown, IL-2 in fetal thymus organ cultures inhibits the normal maturation of fetal thymocytes and raises the question of whether the cytotoxic cells that appear reflect selection through an alternative pathway of development.

Animals↗
PubMed1987

Interleukin 2 regulates the expression of IL 2 receptors on interleukin 3-dependent bone marrow-derived cell lines.

Two IL 3-dependent bone marrow-derived cell lines, FD.C/1 and 32Dcl-23, have been converted to IL 2-dependent growth states. In the case of the FD.C/1 cell line, a small subpopulation of cells converted to IL 2 growth dependence, whereas for the 32Dcl-23 cell line, most cells readily converted to IL 2 growth dependence. IL 2 receptor expression was followed in FD.C/1 and 32Dcl-23 cells in both IL 3-and IL 2-dependent growth states, by analyzing transcription of IL 2 receptor-specific RNA and the subsequent expression of cell surface receptors. The exposure of IL 3-dependent cell lines to IL 2 resulted in rapid increases in the transcription of IL 2 receptor-specific RNA and receptor expression. The addition of IL 3 to IL 2-dependent cell lines did not alter the expression of the IL 2 receptor. When IL 2 was removed from the culture medium of these cells, the presence of IL 3 maintained a higher level of IL 2 receptor expression than was observed in the absence of lymphokines.

Animals↗
PubMed1987

Expression of genes in cloned murine cell lines that can be maintained in both interleukin 2- and interleukin 3-dependent growth states.

Two cloned murine cell lines, FD.C/1 and 32Dcl-23 exhibit switching of lymphokine-dependent growth states. The bone marrow-derived FD.C/1 and 32Dcl-23 cell lines are normally grown in culture medium supplemented with interleukin 3 (IL3). The replacement of IL3 with interleukin 2 (IL2) in the medium results in an increase in IL2 receptor expression in FD.C/1 and 32Dcl-23 cells and the switching of cells to an IL2-dependent growth state. We have compared patterns of protein and phosphoprotein synthesis, as well as the expression of the c-abl, c-ras, c-myb, and c-fos oncogenes in these cell lines maintained in IL3- and IL2-dependent growth states. The synthesis of a series of proteins and phosphoproteins are identified with each of the lymphokine-dependent growth states. All of the oncogenes examined are expressed in both IL2- and IL3-dependent cells and are not altered by phenotypic changes in lymphokine growth dependence. The relationship of oncogene expression to intracellular pathways regulated by lymphokine-receptor interactions is considered.

Animals↗
PubMed1987

Nature and specificity of lymphokine independence induced by a selectable retroviral vector expressing v-src.

A murine retroviral vector, LSNLsrc, has been constructed and examined for its ability to induce growth factor independence in cells normally dependent on interleukin 2 (IL-2) or interleukin 3 (IL-3) for growth. The LSNLsrc vector coexpressed the v-src gene of Rous sarcoma virus and the neo gene from transposon Tn5, allowing infected cells to be selected on the basis of G418 resistance. The murine cell lines CTLL-2 and FD.C/1, which are dependent for growth on IL-2 and IL-3, respectively, were both readily infected with the LSNLsrc virus. LSNLsrc-infected, G418-resistant cultures of FD.C/1 cells were able to give rise to IL-3-independent progeny, but all G418-resistant CTLL-2 cells retained normal IL-2 dependence. The induction of IL-3 independence by v-src was not a direct event, since limiting dilution analysis of the LSNLsrc-infected FD.C/1 cells showed that most of them were IL-3 dependent, despite expression of v-src mRNA and active pp60v-src kinase. However, clones selected from this population in the presence of IL-3 were able to undergo a subsequent progression event and generate IL-3-independent progeny. The generation of factor-independent variants in the clonal cultures was a rare event, as witnessed by the death of most of the cells in each clone when IL-3 was withdrawn. Together, these data indicate that a secondary event, in addition to v-src expression, was required to generate IL-3-independent growth. No evidence was found for an autocrine mechanism of transformation involving IL-2, IL-3, interleukin 4, or granulocyte-macrophage colony-stimulating factor.

Cell Division↗
PubMed1987

Human granulocyte-macrophage progenitors and their sensitivity to cytotoxins: analysis by limiting dilution.

Limiting dilution analysis of granulocyte-macrophage progenitor cells was performed by using adherent and T cell-depleted normal human bone marrow and the recombinant human growth factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Estimated frequencies for progenitor cells responding to G-CSF were one in 489 for colonies scored at day 7, and one in 1,015 for day 14 colonies. For GM-CSF the frequencies were one in 1,407 (day 7) and one in 574 (day 14). The effects of tumor necrosis factor (TNF) and lymphotoxin (LT) on the frequency of progenitors responding to either G-CSF or GM-CSF was determined. Both TNF and LT inhibited the response of cells to G-CSF, and in these cultures the frequency of progenitor cells that responded to G-CSF was reduced to less than one in 100,000 cells. In contrast, the frequency of cells able to form colonies in cultures stimulated with GM-CSF was unaltered by either cytotoxin. This differential sensitivity to cytotoxins suggests that either G-CSF and GM-CSF are acting on separate granulocyte progenitor populations or that TNF and LT selectively influence the biochemical pathways associated with the activation of receptors for G-CSF.

Bone Marrow Cells↗
PubMed1986

Purification to homogeneity of a human hematopoietic growth factor that stimulates the growth of a murine interleukin 3-dependent cell line.

A human lymphokine derived from the 5637 bladder carcinoma has been purified to homogeneity by using sequential reverse-phase high pressure liquid chromatography. A high recovery of biological activity is obtained by using this purification. The NH2-terminal amino acid sequence shows no homology to human interleukin 1 (IL 1), human IL 2, murine IL 3, or human granulocyte-macrophage colony-stimulating factor. The growth-promoting properties of the 5637-derived factor can be rapidly assayed by using the murine IL 3-dependent 32D c1-23 cell line. The amino acid sequence described is identical to that recently described for a human granulocyte colony-stimulating factor.

Animals↗
PubMed1986

Prophylaxis with tinidazole of infection in major head and neck surgery for malignant disease.

In a double-blind study, 20 patients undergoing surgery for the removal of an oropharyngeal squamous carcinoma received tinidazole either as a single perioperative prophylactic dose of 2 g or as a treatment course of 8 g given over a 7 day period. The wounds were assessed daily and specimens of fluid from the upper neck drain were submitted for culture. Four patients, two in each group, developed complications that might have been associated with infection (flap necrosis, fistula formation or both). There was no significant difference in the efficacy of these two regimens and single dose prophylaxis with tinidazole is advocated.

Adult↗
PubMed1986

Biochemical characterization of circulating Met-enkephalins in canine endotoxin shock.

The alterations in arterial, venous and adrenal vein levels of immunoreactive Met-enkephalins following endotoxin administration have been investigated in dogs by direct measurement and gel filtration chromatography. Animals were anaesthetized with alpha-chloralose and allowed to breath spontaneously. The left lumbar adrenal vein, limb vein and femoral artery were cannulated for blood sampling. Severe shock was produced by the administration of a large bolus of E. coli endotoxin followed by a continuous infusion. The production of endotoxin shock was associated with significant increases in adrenal vein and systemic venous plasma immunoreactive Met-enkephalin levels. Forty-five minutes after induction of endotoxin shock arterial immunoreactive Met-enkephalin levels were generally higher than baseline values. In resting anaesthetized animals a large 31,000 molecular weight form of Met-enkephalin, presumably proenkephalin, was found in plasma obtained from the adrenal vein, systemic and pulmonary circulations. Following endotoxin this enkephalin-containing peptide still predominated in arterial and venous plasma, whereas in the adrenal vein the proportion of Met-enkephalin immunoreactivity attributable to this large peptide fell. This was associated with the appearance of increasing amounts of smaller molecular forms (18,000, 8000, 3-5000 molecular weight and the pentapeptide itself). In this model enkephalin-containing peptides were not biochemically modified by their passage through the lungs.

Adrenal Glands↗
PubMed1986

Immunity to leprosy. III. The in vitro induction of B lymphocyte proliferation by mycobacteria.

The development of murine proliferative response assays has been initiated to begin to evaluate T-lymphocyte responses to the antigens of Mycobacterium leprae. In this study, M. leprae and 13 related strains of mycobacteria have been tested for stimulatory effects in proliferation assays using murine spleen, thymus or lymph node cultures. A number of mycobacteria were found to directly stimulate the proliferation of spleen and lymph node cells of all mouse strains tested including C3H/HeJ mice. Thymocyte cultures showed no response. The mitogenic effects of mycobacteria in spleen cultures were not dependent upon the presence of T cells or adherent cells, and resulted in the production of antibody-forming cells. Thus, these bacteria acted as polyclonal B-cell mitogens and could be readily distinguished from the lipopolysaccharide of Gram-negative bacteria by their mitogenic activity on C3H/HeJ spleen cells. The species of mycobacteria which exhibit direct mitogenic effects in spleen and lymph node cultures are a particular problem when specific immune responses to the antigens of these bacteria are compared. Such comparisons are necessary if in vitro assays are to be used to determine the nature of crossreactive antigens between M. leprae and other mycobacteria.

Animals↗
PubMed1986

Immunity to leprosy. IV. Murine T-cell proliferative responses to mycobacteria.

The nature of antigens shared between Mycobacterium leprae and other species of mycobacteria has been examined using a murine T-cell proliferation assay. Mice were immunized with different mycobacteria, and lymph node cultures were prepared one week later and challenged with M. leprae antigen. The 13 species of mycobacteria tested as antigens in this assay revealed that several species shared antigens in common with M. leprae as recognized by T-cell responses. C57BL/10J mice and congenic strains exhibit differences in T-cell responsiveness to M. leprae. B10.M and B10.Q mice are high responders and C57BL/10J are low responders, while F1 (C57BL/10J X B10.M) and (C57BL/10J X B10.Q) hybrid progeny are also low responders. These genetic differences were not observed when six other mycobacterial species were used as T-cell antigens. An unexpected finding was that the genetic pattern of T-cell responsiveness to M. marinum was identical to that observed for M. leprae using these strains of mice. Helper T cells may recognize antigenic determinants shared by M. leprae and M. marinum. These antigens may initiate the induction of T-cell responses to these two species of mycobacteria.

Animals↗
PubMed1986

Surgeons' attitudes to some aspects of day case surgery.

The level of day case surgery is much lower in Northern Ireland than in England. A questionnaire was sent to all 55 consultant general surgeons in Northern Ireland to assess attitudes to this form of care and 51 (93%) replied. They were asked about the suitability of five procedures for day surgery. The three minor procedures of vasectomy, cystoscopy and gastroscopy were regarded as suitable or very suitable by 50 (98% of those who replied), 48 (94%) and 48 (94%) respectively. For the two intermediate procedures, 25 (49%) regarded the repair of inguinal hernia as suitable for day case surgery and 22 (43%) ligation of varicose veins. When asked about eight factors limiting their use of day surgery for inguinal hernia repair, the two most frequently rated as important were 'home conditions' and 'level of provision of domiciliary care' (both by 44 (86%) of the surgeons). Of factors which might promote their use of day surgery for this operation the two most important were 'more efficient use of health service resources' (71%) and the 'ability to convalesce at home' (67%). The problem of under-reporting of day cases and the importance of accurate statistics are considered.

Ambulatory Surgical Procedures↗
PubMed1985

Hidradenitis suppurativa--a clinical review.

A retrospective review of 72 patients suffering from hidradenitis suppurativa treated surgically in one plastic surgery unit has been carried out. Treatment of the axilla by excision and suture was found to result in a high rate (54%) of reoperation for recurrence at the same site when compared to the groups treated by either excision and split skin grafting (13%) or excision and local flap cover (19%). It is recommended that axillary hidradenitis suppurativa is best treated surgically by excision of the affected skin and split skin grafting of the resultant defect.

Adolescent↗