Early and Late Effects of H 3 TDR-Labeled DNA on Ileal Cell Replication in Vivo

1968 ◽  
Vol 34 (3) ◽  
pp. 570 ◽  
Author(s):  
Joseph Post ◽  
Joseph Hoffman
Keyword(s):  
Late Effects ◽  
Cell Replication

scholarly journals Insulin Stimulates Primary β-Cell Proliferation via Raf-1 Kinase

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2251-2260 ◽  
Author(s):  
Jennifer L. Beith ◽  
Emilyn U. Alejandro ◽  
James D. Johnson
Keyword(s):  
Cell Proliferation ◽  
Dominant Role ◽  
Cell Mass ◽  
Diabetes Type 2 ◽  
Dominant Negative ◽  
Cell Replication ◽  
Β Cell ◽  
Physiological Control ◽  
Primary Mouse

A relative decrease in β-cell mass is key in the pathogenesis of type 1 diabetes, type 2 diabetes, and in the failure of transplanted islet grafts. It is now clear that β-cell duplication plays a dominant role in the regulation of adult β-cell mass. Therefore, knowledge of the endogenous regulators of β-cell replication is critical for understanding the physiological control of β-cell mass and for harnessing this process therapeutically. We have shown that concentrations of insulin known to exist in vivo act directly on β-cells to promote survival. Whether insulin stimulates adult β-cell proliferation remains unclear. We tested this hypothesis using dispersed primary mouse islet cells double labeled with 5-bromo-2-deoxyuridine and insulin antisera. Treating cells with 200-pm insulin significantly increased proliferation from a baseline rate of 0.15% per day. Elevating glucose from 5–15 mm did not significantly increase β-cell replication. β-Cell proliferation was inhibited by somatostatin as well as inhibitors of insulin signaling. Interestingly, inhibiting Raf-1 kinase blocked proliferation stimulated by low, but not high (superphysiological), insulin doses. Insulin-stimulated mouse insulinoma cell proliferation was dependent on both phosphatidylinositol 3-kinase/Akt and Raf-1/MAPK kinase pathways. Overexpression of Raf-1 was sufficient to increase proliferation in the absence of insulin, whereas a dominant-negative Raf-1 reduced proliferation in the presence of 200-pm insulin. Together, these results demonstrate for the first time that insulin, at levels that have been measured in vivo, can directly stimulate β-cell proliferation and that Raf-1 kinase is involved in this process. These findings have significant implications for the understanding of the regulation of β-cell mass in both the hyperinsulinemic and insulin-deficient states that occur in the various forms of diabetes.

scholarly journals Cyclophosphamide leads to persistent deficits in physical performance and in vivo mitochondria function in a mouse model of chemotherapy late effects

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181086 ◽  
Author(s):  
Marie-Laure Crouch ◽  
Gary Knowels ◽  
Rudolph Stuppard ◽  
Nolan G. Ericson ◽  
Jason H. Bielas ◽  
...  
Keyword(s):  
Mouse Model ◽  
Physical Performance ◽  
Late Effects

scholarly journals Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebeca Fernandez-Ruiz ◽  
Ainhoa García-Alamán ◽  
Yaiza Esteban ◽  
Joan Mir-Coll ◽  
Berta Serra-Navarro ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Proliferation ◽  
Cell Replication ◽  
Trophic Effect ◽  
Beta Cell Replication

AbstractExpanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.

Comparison of in vivo skin and in vitro blood lymphocyte models for the prediction of late normal tissue responses in breast radiotherapy (RT) patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11116-11116
Author(s):  
Melvin Chua ◽  
Navita Somaiah ◽  
Sue Davies ◽  
Lone Gothard ◽  
Kai Rothkamm ◽  
...  
Keyword(s):  
Late Effects ◽  
Normal Tissue ◽  
Ex Vivo ◽  
Predictive Marker ◽  
Dermal Fibroblasts ◽  
Clinical Severity ◽  
Breast Size ◽  
Dsb Repair

11116 Background: Critical opinions for the lack of success of DNA double-strand break (DSB) repair as a predictive marker of normal tissue radiosensitivity include the argument that in vitro cellular responses correlate poorly with in vivo responses due to the modifying influence of tissue environment. In this study, we test the hypothesis that a DNA damage assay based on in vivo irradiated skin tissues better predicts clinical responses in human skin, as opposed to the same assay performed in ex vivo irradiated lymphocytes. Methods: DSB levels (24 h post-4 Gy) were quantified using γH2AX/53BP1 immunostaining in irradiated skin tissues and G0 lymphocytes of 35 breast RT patients. Patients were selected on the basis of late RT effects in their breast and individuals with marked or minimal effects were classified as cases and controls, respectively. Risk factors of late effects established from multivariate analyses of outcomes of two breast RT trials were also considered in patient selection. They were 1) total RT dose, 2) RT dosimetry, 3) tumour bed boost, 4) breast size, 5) surgical cavity, and 6) axillary treatment. Results: Clinical parameters were balanced in both patient groups. Residual foci levels in skin epidermis and dermis were comparable between cases (n = 20) and controls (n = 15). Mean foci per cell were 3.29 in cases, 2.80 in controls for dermal fibroblasts (p = 0.07); 3.28 in cases, 2.60 in controls for endothelial cells (p = 0.08); 2.87 in cases, 2.41 in controls for superficial keratinocytes (p = 0.45); 2.32 in cases, 2.35 in controls for basal keratinocytes (p = 0.27). Residual foci levels in lymphocytes were however significantly higher among cases (foci per cell = 12.1) compared to controls (foci per cell = 10.3, p = 0.01). Of the different cell types, only residual foci levels of dermal fibroblasts and lymphocytes correlated with clinical severity (R = 0.722, p < 0.001; 0.593, p = 0.01, respectively). Interestingly, foci levels were not correlated between skin cells and lymphocytes of the same patients. Conclusions: DSB repair of ex vivo irradiated lymphocytes appears to be a better predictive marker of late effects to breast RT than DSB repair of in vivo irradiated skin.

scholarly journals Granulosa cells of the cumulus oophorus are different from mural granulosa cells in their response to gonadotrophins and IGF-I

2001 ◽  
Vol 170 (3) ◽  
pp. 565-573 ◽  
Author(s):  
F Khamsi ◽  
S Roberge
Keyword(s):  
Granulosa Cells ◽  
Cumulus Cells ◽  
Saline Control ◽  
Cell Replication ◽  
Progesterone Secretion ◽  
Igf I ◽  
Negative Effect ◽  
Positive Effect

There are two types of granulosa cells: those which surround the oocyte are cumulus cells (CC) and those which surround the antrum are mural granulosa cells (MGC). These cells are under the influence of several hormones and growth factors, the most important of which are gonadotrophins and IGF-I. In this article, we report novel observations on the differences between these two types of granulosa cells and their interaction with gonadotrophins and IGF-I. We were able to conduct physiological studies on the role of IGF-I by using an analogue of IGF-I which does not bind to IGF-I-binding proteins (LR3-IGF-I). Immature rats received saline, equine chorionic gonadotrophin (eCG), LR3-IGF-I or eCG plus LR3-IGF-I by infusion using a pump from 24-29 days of age. The rats were killed and the ovaries removed. Surface follicles were punctured and MGC and oocyte cumulus complexes were removed. These were cultured in saline (control) and in three different doses of FSH. Cell replication was assessed by 3H-thymidine incorporation and differentiation was evaluated by the measurement of progesterone secretion. It was noted that CC replicated ten times more than MGC. Similarly, progesterone secretion by CC was six times more than by MGC. In vivo exposure to gonadotrophins (eCG) positively influenced in vitro treatment with FSH in both cell types. This phenomenon was observed in both cell replication and progesterone secretion. The IGF-I analogue had a positive effect on cell replication of MGC but a negative effect on the cell replication of CC. With respect to progesterone secretion, the IGF-I analogue had a negative effect on CC but a positive effect on MGC. In conclusion, CC behaved differently from MGC in response to gonadotrophins and the IGF-I analogue. IGF-I and FSH acted additively, synergistically or antagonistically in different circumstances.

scholarly journals Mediators of Anaphylaxis, Anaphylactoid Reactions, and Rhinitis

1987 ◽  
Vol 1 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Kenneth P. Mathews
Keyword(s):  
Mast Cells ◽  
Allergic Reaction ◽  
Late Effects ◽  
Late Phase ◽  
Allergic Reactions ◽  
Cellular Interactions ◽  
Nasal Symptoms ◽  
Anaphylactoid Reactions

Besides histamine, a large and increasing number of mediators of allergic reactions are being found to be released by mast cells or basophils during anaphylactic reactions. Many of these same substances are released by stimuli other than allergen-IgE interactions, and this type of phenomenon (anaphylactoid or pseudo-allergic reaction) may account for some nasal symptoms that simulate allergy. In addition to rapidly developing reactions of these types, numerous recent investigations have emphasized the importance of late-phase reactions that occur as a consequence of the immediate reactivity. Besides mast cells and/or basophils, these late effects seem to involve a complex network of cellular interactions, which may include neutrophils, eosinophils, lymphocytes, macrophages, and platelets. Studies of nasal washings following allergen challenges in humans have provided cogent in vivo support of earlier hypotheses about mediator release based on in vitro experimentation.

Cloning of nascent monkey DNA synthesized early in the cell cycle

1985 ◽  
Vol 5 (4) ◽  
pp. 721-727
Author(s):  
G Kaufmann ◽  
M Zannis-Hadjopoulos ◽  
R G Martin
Keyword(s):  
Dna Synthesis ◽  
Animal Cell ◽  
S Phase ◽  
Cell Replication ◽  
Mung Bean Nuclease ◽  
Base Pairs ◽  
African Green Monkey Kidney ◽  
Green Monkey ◽  
Cellular Dna

To study the structure and complexity of animal cell replication origins, we have isolated and cloned nascent DNA from the onset of S phase as follows: African green monkey kidney cells arrested in G1 phase were serum stimulated in the presence of the DNA replication inhibitor aphidicolin. After 18 h, the drug was removed, and DNA synthesis was allowed to proceed in vivo for 1 min. Nuclei were then prepared, and DNA synthesis was briefly continued in the presence of Hg-dCTP. The mercury-labeled nascent DNA was purified in double-stranded form by extrusion (M. Zannis-Hadjopoulos, M. Perisco, and R. G. Martin, Cell 27:155-163, 1981) followed by sulfhydryl-agarose affinity chromatography. Purified nascent DNA (ca. 500 to 2,000 base pairs) was treated with mung bean nuclease to remove single-stranded ends and inserted into the NruI site of plasmid pBR322. The cloned fragments were examined for their time of replication by hybridization to cellular DNA fractions synthesized at various intervals of the S phase. Among five clones examined, four hybridized preferentially with early replicating fractions.

scholarly journals In Vivo Engineering of the Vocal Fold ECM With Injectable HA Hydrogels—Late Effects on Tissue Repair and Biomechanics in a Rabbit Model

2011 ◽  
Vol 25 (2) ◽  
pp. 249-253 ◽  
Author(s):  
Susan L. Thibeault ◽  
Sarah A. Klemuk ◽  
Xia Chen ◽  
Beatriz H. Quinchia Johnson
Keyword(s):  
Late Effects ◽  
Tissue Repair ◽  
Vocal Fold ◽  
Rabbit Model
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