Uptake and biodistribution of dopamine in bone marrow, spleen and lymph nodes of normal and tumor bearing mice

Life Sciences ◽  
1993 ◽  
Vol 53 (5) ◽  
pp. 415-424 ◽  
Author(s):  
Sujit Basu ◽  
Partha Sarathi Dasgupta ◽  
Twisha Lahiri ◽  
Jayasree Roy Chowdhury
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Tumor Bearing ◽  
Spleen And Lymph Nodes

scholarly journals BONE MARROW AS SOURCE OF CELLS IN REACTIONS OF CELLULAR HYPERSENSITIVITY

1968 ◽  
Vol 128 (6) ◽  
pp. 1437-1449 ◽  
Author(s):  
David M. Lubaroff ◽  
Byron H. Waksman
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Skin Test ◽  
Skin Tests ◽  
Skin Reactions ◽  
Lewis Rats ◽  
Lymph Node Cells ◽  
Lymphocyte Transfer ◽  
Spleen And Lymph Nodes

The precise origin of cells infiltrating tuberculin skin reactions was studied with the technique of immunofluorescence. Thymectomized, irradiated Lewis rats were restored with bone marrow from allogeneic or F1 donors. They were passively sensitized to tuberculin by a subsequent transfer of Lewis lymph node cells and were given intradermal skin tests with tuberculoprotein. In 24 hr reactions the majority of cells were shown to be derived from the infused marrow. These results were the same regardless whether the lymphocyte transfer was performed on the day of irradiation and marrow injection or 7 days later. The cells in the tuberculin reactions, marrow, spleen, and lymph nodes not derived from the bone marrow were found to originate in the transferred lymph node cells. The relative percentages of marrow-derived and lymph node-derived cells in the tuberculin reactions remained the same during the 9–24 hr period following skin test.

Marqibo (Vincristine Sulfate Liposomes Injection, OPTISOME™) Concentrates Vincristine in Tumor Tissue and Lymphoid Malignancy Oriented Tissues in Tumor-Bearing Mice.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1403-1403 ◽  
Author(s):  
Pieter R. Cullis ◽  
Hagop Kantarjian ◽  
Frederick Appelbaum ◽  
Susan O’Brien ◽  
May Wong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Tumor Tissue ◽  
Parent Compound ◽  
Whole Body ◽  
Cancer Drug ◽  
Vincristine Sulfate ◽  
Tumor Bearing ◽  
Drug Concentrations ◽  
Anti Cancer

Abstract Background: Vincristine sulfate (VCR) is a cell-cycle specific, lipophilic, anti-cancer drug that inhibits cell division by binding to tubulin in mitotic spindles. Marqibo is a proprietary sphingomyelin/cholesterol liposome (OPTISOME) encapsulated formulation of VCR with an extended circulating half-life and the potential for preferential malignancy targeting, exposure, and anti-cancer activity. This report evaluates the concentration and accumulation of VCR in solid tumor tissue as well as tissues frequently involved with lymphoid malignancies in tumor-bearing mice following equivalent doses of Marqibo or conventional VCR. Methods: Mice were implanted subcutaneously with MX-1 human breast tumor tissue. When the tumor volume reached 162–485 mm3, mice received a single intravenous dose of Marqibo, containing 1.5 mg/kg of [14C]-VCR, or 1.5 mg/kg of non-liposomal [14C]-VCR. The total radioactivity from parent compound and metabolites in tissue, VCReq, was analyzed by Quantitative Whole Body Autoradioluminography (QWBA) and tissue digestion (TD). QWBA analysis of bone marrow (BM), tumor tissue, lymph nodes, liver, and spleen required 1 flash-frozen mouse per group at various time intervals. Sagittal sections were examined histologically for radioactivity. For TD, all tissues except bone marrow were obtained from 3 mice per group prior to infusion and at selected time points. The samples were chemically digested and analyzed for radioactivity by liquid scintillation counting. Results: QWBA analysis revealed at least two-fold higher VCReq tissue concentrations in the Marqibo-injected mice compared to the conventional VCR-injected mice. VCReq Tissue Concentration (mcg/g) at 48 hours Post-Injection BM Tumor Lymph Liver Spleen Marqibo 0.99 1.35 1.98 0.47 6.08 VCR 0.36 0.31 -- 0.13 0.76 Marqibo/VCR ratio 2.75 4.35 -- 3.61 8 The TD results are consistent with the QWBA results shown in the table. Marqibo-injected mice demonstrated a minimum 5-fold increase in VCR exposure over a 96 hour period (VCReq AUC analysis) compared to VCR-injected mice over a 48 hour period, as defined in the parameters of the study, in the implanted tumor (123 vs. 21 hr*μg/g), lymph nodes (121 vs. 16.5 hr*μg/g), liver (68.8 vs. 12 hr*μg/g), and spleen (512 vs. 68.9 hr*μg/g). Though the parameters for the AUC values may favor Marqibo, the Tmax of all specified tissues are at least 16 times greater in Marqibo-injected mice than in VCR-injected mice (16 hrs vs. 1hr in tumor, spleen, and lymph; 4 hrs vs. 15 min. in liver; 16 hrs. vs. 15 min. in the kidney). The greatest increase in VCR exposure produced by Marqibo was observed in the spleen and lymph nodes (7.4- and 7.3-fold). Conclusions: Marqibo resulted in targeted delivery of VCR; concentration of VCR in tumor tissue, BM, lymph nodes, liver, and spleen; and maintenance of significant tissue drug concentrations for an extended period of time compared to conventional VCR. The ability of Marqibo to target drug to these tissues and organs makes it particularly attractive as a treatment for hematologic malignancies like myeloma, lymphoma, and acute lymphoblastic leukemia (ALL). Late-stage clinical development of Marqibo in adult ALL is underway.

scholarly journals Deletion of Cellular Prion Protein (PrPC) Results in Peripheral Lymphocytosis and Larger Platelets

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4619-4619
Author(s):  
Yan Zheng ◽  
Guangyuan Li ◽  
Menglei Zhu ◽  
Yu Li ◽  
Howard Meyerson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Blood Count ◽  
Complete Blood Count ◽  
Absolute Lymphocyte Count ◽  
Cellular Prion Protein ◽  
Platelet Volume ◽  
Spleen And Lymph Nodes

Abstract Cellular prion protein (PrPC) is a GPI-anchored cell surface glycoprotein that is expressed in the brain, blood, bone marrow (BM), and lymphoid tissue. PrPC can be converted post-translationally into scrapie-PrP (PrPSc), which is involved in the pathogenesis of neurodegenerative diseases including Creutzfeldt-Jakob disease, Kuru disease in humans, and scrapie and bovine spongiform encephalopathy in animals. However, the biological function of PrPSc has yet to be conclusively elucidated. In order to understand the role of PrPC in the hematopoietic system, we compared bone marrow, lymphoid organs and peripheral blood of PrPC knockout mice (KO) to age and sex-matched transgenic mice used as background controls (WT) expressing human PrPC under the control of a mouse PrPC promoter with a slightly augmented expression (2-fold) of PrPC. Complete blood count (CBC) showed a significant increase of WBC in KO mice (KO 9.03 ± 5.16 x109/L vs. WT 4.13 ± 1.87 x109/L, p = 0.0405; Table 1 and Figure 1). Further analysis of WBC differential revealed that the elevated number of WBC in KO mice was due to lymphocytosis. Specifically, KO mice had a 3-fold increase in the absolute lymphocyte count (KO 7.59 ± 4.63 x109/L vs. WT 2.90 ± 1.32 x109/L, p = 0.0303), as well as a higher lymphocyte percentage (KO 82.47 ± 4.20% vs. WT 70.19 ± 4.44%, p = 0.0011) compared to controls. KO mice also had a trend toward higher hemoglobin (KO 12.00 ± 4.40 g/dL vs. WT 9.84 ± 4.83 g/dL), RBC (KO 8.01 ± 2.87 x1012/L vs. WT 6.25 ± 3.11 x1012/L), and hematocrit (KO 43.94 ± 17.00 % vs. WT 36.04 ± 18.07 %) compared to WT mice. Additionally, platelet count in KO mice was higher than control mice (KO 762.20 ± 138.61 x 109/L vs. WT 661.80 ± 230.20 x 109/L). Of interest, the mean platelet volume (platelet size) was significantly increased in KO mice compared to controls (KO 6.00 ± 0.29 fL vs. WT 5.24 ± 0.56 fL, p =0.0140). Thus, absence of PrPC resulted in significant leukocytosis and specifically higher absolute count and percentage of lymphocytes, as well as larger platelets in peripheral blood. To further analyze if the observed lymphocytosis is due to abnormalities in hematopoiesis or lymphopoiesis, bone marrow (BM), thymus, spleen and lymph nodes from WT and KO mice were isolated and examined by flow cytometry using a comprehensive panel of fluorochrome-conjugated antibodies specific for all hematologic cell precursors/lineages. Analysis of all cell populations in each of these organs revealed no significant differences in the numbers of RBC and megakaryocyte in BM, and of lymphocytes in the thymus, spleen and lymph nodes (data no shown). Additionally, histological analysis of BM, thymus, spleen and lymph nodes tissue from KO and WT animals failed to show morphological differences between the two groups (data not shown). Therefore, lack of PrPC does not appear to affect hematopoiesis and lymphopoiesis. In summary, our findings indicate that PrPC deficiency translates into a significant increase in the number of lymphocytes in peripheral blood; however, development and maturation of lymphocytes in KO mice appeared normal. Therefore, PrPC might be critical in the survival and trafficking of lymphocytes in peripheral blood. The molecular mechanisms underlying the observed changes in lymphocytes and platelets, and whether there are any related changes in the functions of lymphocytes and platelets will be subject of future studies. Table 1. Complete blood count (CBC) of PrPC WT and KO mice WT KO p value Mean ± SD Mean ± SD WBC (109/L) 4.13 ± 1.87 9.03 ± 5.16 0.0405 Absolute lymphocyte count (109/L) 2.90 ± 1.32 7.59 ± 4.63 0.0303 Lymphocyte (%) 70.19 ± 4.44 82.47 ± 4.20 0.0011 RBC (1012/L) 6.25 ± 3.11 8.01 ± 2.87 0.1898 HB (g/dL) 9.84 ± 4.83 12.00 ± 4.40 0.2404 HCT (%) 36.04 ± 18.07 43.94 ± 17.00 0.2618 PLT (109/L) 661.80 ± 230.20 762.20 ± 138.61 0.2138 MPV (fL) 5.24 ± 0.56 6.00 ± 0.29 0.0140 SD: Standard deviation; WBC: White blood cell; RBC: Red blood cell; HB: Hemoglobin; HCT: Hematocrit; RDW: Red cell distribution width; PLT: Platelet; MPV: Mean platelet volume Figure 1. PrPC deficiency results in lymphocytosis in peripheral blood. Figure 1. PrPC deficiency results in lymphocytosis in peripheral blood. Disclosures No relevant conflicts of interest to declare.

scholarly journals Peripheral engraftment of fetal intestine into athymic mice sponsors T cell development: direct evidence for thymopoietic function of murine small intestine.

1992 ◽  
Vol 176 (5) ◽  
pp. 1365-1373 ◽  
Author(s):  
R L Mosley ◽  
J R Klein
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
T Cell Development ◽  
Peripheral T Cells ◽  
Alpha Beta ◽  
Spleen And Lymph Nodes ◽  
Cell Repopulation ◽  
Fetal Intestine

Adult athymic, lethally irradiated, F1-->parent bone marrow-reconstituted (AT x BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT x BM-SHAM) were essentially void of T cells, whereas in AT x BM thymus-engrafted (AT x BM-THG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT x BM fetal intestine-engrafted (AT x BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT x BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-alpha/beta+ T cells with both CD4+8- and CD4-8+ subsets. Peripheral T cells in AT x BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3 epsilon. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT x BM-FIG and AT x BM-THG mice, though not in spleen cell cultures from AT x BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (Tl) antigens were expressed on epithelial surfaces of intestine grafts, and that both TCR-alpha/beta+ and TCR-gamma/delta+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.

scholarly journals IMMUNOGLOBULINS ON THE SURFACE OF LYMPHOCYTES

1971 ◽  
Vol 133 (6) ◽  
pp. 1188-1198 ◽  
Author(s):  
Emil R. Unanue ◽  
Howard M. Grey ◽  
Enrique Rabellino ◽  
Priscilla Campbell ◽  
Jon Schmidtke
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Bone Marrow Cells ◽  
Live Cells ◽  
Light Chains ◽  
Adult Mice ◽  
Normal Number ◽  
Spleen Lymphocytes ◽  
Spleen And Lymph Nodes ◽  
Two Populations

Immunofluorescent studies using live cells from antibody-forming organs and anti-immunoglobulin antibodies demonstrate two populations of small lymphocytes which are differentiated by the presence or absence of Ig on their surface membranes. Most of the lymphocytes with detectable surface Ig appear to derive from cells of the bone marrow, while most of the Ig-negative lymphocytes derive from the thymus. Thus, adult mice thymectomized, lethally irradiated, and transplanted with bone marrow cells showed a normal number of lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes. Injection of thymocytes into these mice did not result in an increase in the number of lymphocytes with surface Ig in spleen and lymph nodes. Most of the injected thymocytes could be identified by means of histocompatibility markers. Also, the spleen and lymph nodes of neonatally thymectomized mice contained lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes. Attempts were made to identify light chains on thymocytes by a sensitive radioimmunoassay. In some experiments no light chains were detected and in others a small amount, i.e. no more than 2.6% of the amount present on spleen lymphocytes, could be detected. Whether these low figures are significant or represent a small amount of serum contamination is not clear as yet.

PRESENCE OF PLASMA CELLS AND γ1M-GLOBULIN SYNTHESIS IN A PATIENT WITH THYMIC ALYMPHOPLASIA

PEDIATRICS ◽  
1966 ◽  
Vol 37 (3) ◽  
pp. 485-492
Author(s):  
Philip Fireman ◽  
Horton A. Johnson ◽  
David Gitlin
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Plasma Cells ◽  
Peripheral Circulation ◽  
Serum Concentrations ◽  
Normal Numbers ◽  
Bone Marrow Plasma ◽  
Severe Infections ◽  
Spleen And Lymph Nodes

A child is described who had thymic alymphoplasia with increased serum concentrations of γ1M-globulins and a deficiency of γ1A- and 7S γ2-globulins; the child was subject to severe infections from 2 weeks of age and succumbed to pneumonia at 11 months of age. Even though the tissues of this patient at necropsy revealed a remarkable paucity of lymphocytes, there were relatively normal numbers of lymphocytes in his peripheral circulation and his bone marrow. Plasma cells were readily demonstrated in the spleen and lymph nodes. The studies suggest that the development of plasma cells and γ1M-globulin synthesis may occur independently of the development of the thymus and the small lymphocytes in man.

scholarly journals PROLIFERATION OF DONOR MARROW AND THYMUS CELLS IN THE MYELOID AND LYMPHOID ORGANS OF IRRADIATED SYNGENEIC HOST MICE

1973 ◽  
Vol 137 (2) ◽  
pp. 543-546 ◽  
Author(s):  
Akikazu Takada ◽  
Yumiko Takada
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Bone Marrow Cells ◽  
The Other ◽  
Host Bone ◽  
Donor Type ◽  
Dividing Cells ◽  
Spleen And Lymph Nodes ◽  
Thymus Cells ◽  
Marrow Cells

CBA/HT6T6 bone marrow cells (1 x 107) or CBA/H bone marrow cells (1 x 107) plus CBA/HT6T6 thymus cells (5 x 107) were injected intravenously into lethally (800 R) irradiated CBA/H mice. Chromosome analyses of dividing cells in the host lymphoid and myeloid organs were performed at intervals after irradiation. Donor marrow cells settled and proliferated in the host bone marrow, spleen, and lymph nodes soon after injection, but donor marrow cells did not proliferate in the host thymus until day 10; then host-type cells were quickly replaced by donor-type cells in the thymus by day 20. On the other hand, donor thymus cells settled and proliferated in the host thymus and lymph nodes soon after injection but they gradually disappeared from these organs. On day 20, a few donor-type dividing cells (of thymus origin) were found in the host lymphoid and myeloid organs.

Sentinel lymph node diagnostic in prostate carcinoma: Part II: Biokinetics and dosimetry of 99mTc-Nanocolloid after intraprostatic injection

2002 ◽  
Vol 41 (02) ◽  
pp. 102-107 ◽  
Author(s):  
J. Kopp ◽  
H. Vogt ◽  
F. Wawroschek ◽  
S. Gröber ◽  
R. Dorn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Urinary Bladder ◽  
Lymph Nodes ◽  
Effective Dose ◽  
Residual Activity ◽  
Tracer Uptake ◽  
Lymphatic Transport ◽  
Radionuclide Distribution ◽  
Radioactivity Uptake

Summary Aim: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the radiotracer into the parenchyma of the prostate. The activity was deposited in liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The aim of this work is to determine biokinetical data and to estimate radiation doses to the patient. Methods: The patients with prostate cancer received a sonographically controlled, transrectal administration of 99mTc-Nanocoll®, injected directly into both prostate lobes. In 10 randomly selected patients radionuclide distribution and its time course was determined via regions of interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph nodes. The uptake in the SLNs was estimated from gamma probe measurements at the surgically removed nodes. To compare tumour positive with tumour free lymph nodes according to SLN-uptake and SLNlocalisation we evaluated 108 lymph nodes out of 24 patients with tumour positive SLN. For calculating the effective dose according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1 software. Results: The average uptake of separate organs was: bladder content 24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied activity remained in the prostate. The residual activity was mainly accumulated in bone marrow and blood. Occasionally a weak activity enrichment in intestinal tract and kidneys could be recognized. The effective dose to the patient was estimated to 7.6 μSv/MBq. The radioactivity uptake of the SLN varied in several orders of magnitude between 0.006% and 0.6%. The probability of SLN-metastasis was found to be independent from tracer uptake in the lymph node. The radioactivity uptake of the SLNs in distinct lymph node regions showed no significant differences. Conclusion: The radiotracer is transferred out of the prostate via blood flow, by direct transfer via the urethra into the bladder and by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in lymph nodes as the only criterion to characterize SLNs.

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