Growth regulation of cells grown in suspension culture.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Watson.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Membrane vesicles can be prepared from murine lymphoid cells by nitrogen cavitation and fractionated by sedimentation through nonlinear sucrose density gradients. Two subpopulations of membrane vesicles, PMI and PMII, can be distinguished on the basis of sedimentation rate. The subcellular distribution of adenylate and guanylate cyclases in these membrane subpopulations have been compared with the distribution of a number of marker enzymes. Approximately 20-30% of the total adenylate and guanylate cyclase activity is located at the top of the sucrose gradient (soluble enzyme), the remainder of the activity being distributed in the PMI and PMII fractions (membrane-bound enzyme). More than 90% of the 5'-nucleotidase and NADH oxidase activities detected in lymphoid cell homogenates are located in PMI and PMII fractions, whereas succinate cytochrome c reductase activity is detected only in the PMII fractions. In addition, beta-galactosidase activity is distributed in the soluble and PMII fractions of the sucrose density gradients. On the basis of the fractionation patterns of these various enzyme activities, it appears that PMI fractions contain vesicles of plasma membrane and endoplasmic reticulum, whereas PMII fractions contain mitochondria, lysomes, and plasma membrane vesicles. Approximately 30-40% of the adenylate and guanylate cyclase activities in PMII can be converted to a PMI-like form following dialysis and resedimentation through a second nonlinear sucrose gradient. Adenylate and guanulate cyclases can be distinguished on the basis of sensitivity to nonionic detergents.
The mechanism was investigated underlying the activity of bacterial lipopolysaccharide (LPS) as an adjuvant of antibody formation as assessed by its capacity to modulate the induction of tolerance in mice to the antigen human Ig G (HGG) into a state of immunity to HGG. The adjuvant activity of LPS was found to be closely correlated with its ability to function as a B-cell mitogen. This correlation was revealed by an analysis of the genetic control of the mitogenic and adjuvant properties of LPS utilizing the refractory state inherent in the C3H/HeJ mouse strain to these activities of LPS. Thus, mice that were the progeny of a backcross between the nonresponder C3H/JeJ parent and the responder (C3H/HeJ X CWB) F1 hybrid were individually typed for responsiveness to LPS, as an adjuvant and as a B-cell mitogen. It was found that LPS interfered with tolerance induction to HGG in vivo only in those backcross progeny whose spleen cells were also capable of responding mitogenically to LPS in vitro, demonstrating that the adjuvant and B-cell mitogenic properties of LPS are genetically linked. In contrast, these properties were observed to segregate independently from either H-2 or heavy chain allotype loci, and were not sex linked. These results are compatible with the concepts that, in this system, (a) the cellular site of action of LPS as an adjuvant is confined to B cells, and (b) the subcellular mode of action of LPS as an adjuvant may involve the delivery of a "signal" to B cells which is a stimulus for mitogenesis.
Explore the source record for details and available documents.
The elongation of Types II and III gold alloys ranges from 20 to 35 per cent. It has therefore been proposed that a nonbeveled margin could be "pulled" (elongation) to close the margin. However, in clinical practice, it is difficult to pull gold over an unsupported space to close the margin. Furthermore, the thin area of gold that would be pulled toward the margin could easily be sheared or abraded during finishing. Malleting or swaging a beveled margin is a more sucessful technique of adapting cast gold to the cavosurface angles.
Explore the source record for details and available documents.
Slices of porcine endometrium and corpus luteum tissue obtained from mature sows throughout the luteal phase of the oestrous cycle were incubated in culture medium which was analysed at regular intervals over a period of 8 hours for prostaglandin F and progesterone. Prostaglandin F secretion was greatest by endometrium obtained during the mid III to late I luteal stage of the cycle and the increased levels secreted by this tissue were paralleled by high levels of secretion from corpus luteum tissue. The addition of indomethacin (10 mug/ml) to the culture medium completely abolished prostaglandin F secretion by both endometrium and luteal tissue indicating that the high levels of the prostaglandin were due to synthesis. Progesterone secretion by the corpus luteum was maximal from early luteal tissue and had declined to considerably lower levels by late stage tissue when prostaglandin secretion was greatest. The possible physiological significance of luteal prostaglandin F secretion is discussed.
The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.
Explore the source record for details and available documents.
Murine lymphocytes incubated with specific mitogens were examined for alterations in levels of intracellular cyclic AMP and cyclic GMP. Mitogenic concentrations of LPS elevate cyclic GMP levels; however, DxSO4, Poly I:C, PPD, Con A, and PHA show little immediate effect on cyclic GMP levels. Higher concentrations of all of these mitogens consistently elevate cyclic AMP levels. Exogenous cyclic GMP stimulates DNA synthesis in homozygous nude (nu/nu) spleen cultures but not in murine thymocyte cultures. Both LPS and cyclic GMP enhance the mitogenic response of thymocytes in the presence of suboptimal concentrations of Con A. Exogenous cyclic AMP inhibits mitogenic responses to both LPS and Con A; however, these inhibitory effects are partially reversed when cyclic GMP is also added to cultures. The mitogenic response of nu/nu spleen cells to LPS can be inhibited by high concentrations of Con A. This inhibition by Con A is also partially reversed by cyclic GMP, indicating that Con A may exert its effect by elevating intracellular levels of cyclic AMP. Thus, while lymphocytee mitogens may affect intracellular levels of both cyclic AMP and cyclic GMP, three effects show a consistent pattern. 1) Exogenous cyclic GMP is either mitogenic for B cells or agents that elevate cyclic GMP levels enhance the mitogenic response of T cells to Con A. 2) Increasing cyclic AMP levels inhibit cell proliferation induced by both B and T cell mitogens. 3) The inhibitory effects of cyclic AMP or cyclic AMP-elevating agents on mitogen-induced proliferation can be partially reversed by the presence of cyclic GMP. The opposing effects of these two cyclic nucleotides may reflect either their involvement in the initiation of cell proliferation or thei modulating effects on cell cycle events after the initiation process has been completed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The intracellular ratio of adenosine 3',5'-cyclic monophosphate (cyclic AMP) to guanosine 3',5'-cyclic monophosphate (cyclic GMP) may control the developmental pathway followed by antibody-forming cell (AFC) precursors. The evidence for this is derived from several different types of experiments. First lipopolysaccharide (LPS) which is mitogenic for B lymphocytes, stimulates rapid, transient changes in intracellular levels of cyclic GMP but not cyclic AMP when added to mouse spleen cultures. Cyclic GMP itself stimulates DNA synthesis in these cultures, suggesting that the intracellular changes in cyclic GMP levels are involved in the mitogenic signal delivered by LPS to cells. The absolute amounts of cyclic nucleotides may vary widely in different cells under various conditions, however, the intracellular ratio of cyclic AMP to cyclic GMP is always high in nondividing cells and low in dividing cells. AFC precursors appear to respond to antigen in the absence of T-cell activity by inactivation (1-7). In the response to antigen in the presence of specific T cells, precursor cells proliferate and mature to AFC. Raising intracellular levels of cyclic AMP inhibits cell proliferation and leads to precursor cell inactivation (14, 15). It is suggested that the interaction of antigen with immunoglobulin receptors on the surface of precursors cells leads to the stimulation of adenylate cyclase activity and initiates the inactivation pathway. Since cyclic GMP stimulates immune responses in T-cell-depleted cultures (14, 15) and increasing cyclic GMP levels appear to be involved in the delivery of a mitogenic signal to cells, it is suggested that T-helper cells deliver a signal to precursor cells via the stimulation of guanylate cyclase to initiate the inductive pathway. It is suggested that it is the intracellular ratio of cyclic AMP to cyclic GMP that regulates the fate of precursor cells, not the absolute level of one cyclic nucleotide.
Explore the source record for details and available documents.
In view of Pigott's work, it would appear that a pharyngoplasty without prior pharyngoscopy is similar to an operation on the bladder without cystoscopy. Now that a simple method of recording, which we consider invaluable, is available, we hope that nasal pharyngoscopy will become a routine examination in patients with speech defects.
A modified superfusion technique is described with which it was demonstrated that the action of gonadotrophin on progesterone secretion by pig corpus luteum tissue is twofold, in that it first stimulates the rapid release of progesterone (either performed or partially synthesized), which is followed by prolonged synthesis of the steroid de novo from acetate.