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M L Patchen

Publications and source records attributed to M L Patchen.

At least 55 records · Page 3Linked to original sources
PubMed1988

Leukotriene-induced radioprotection of hematopoietic stem cells in mice.

Leukotrienes (LTs), known primarily for their pathological roles, may also be capable of exerting "cytoprotection" against toxic agents in a manner similar to that of prostaglandins. In this report, it is shown that treatment of mice with leukotrienes C4, D4, E4, or B4 prior to sublethal irradiation increased the number of endogenous hematopoietic stem cells (E-CFU), with LTC4 producing the greatest response (LTC4 much greater than B4 greater than E4 greater than D4). LTC4-induced hematopoietic radioprotection was examined in greater detail using the exogenous spleen colony (CFU-S) and granulocyte/macrophage progenitor cell (GM-CFC) assays. The dose reduction factors for these cells in LTC4-treated mice at radiation doses resulting in 37% cell survival were 1.65 and 2.01, respectively.

Animals↗
PubMed1988

Recovery of hematopoietic colony-forming cells in irradiated mice pretreated with interleukin 1 (IL-1).

Data in this report determined the effect of a single injection of recombinant interleukin 1 alpha (rIL-1) prior to irradiation of B6D2F1 mice on the recovery of colony-forming cells (CFC) at early and late times after sublethal and lethal doses of radiation. Injection of rIL-1 promoted an earlier recovery of mature cells in the blood and CFC in the bone marrow and spleen. For example, 8 days after 6.5 Gy irradiation, the number of CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units-erythroid), and GM-CFC (granulocyte-macrophage colony-forming cells) per femur was approximately 1.5-fold higher in rIL-1-injected mice than in saline-injected mice. Also, 5, 9, and 12 days after irradiation, the number of both day 8 and day 12 CFU-S (colony-forming units-spleen) was almost twofold greater in bone marrow from rIL-1-injected mice. The earlier recovery of CFU-S in rIL-1-injected mice was not associated with an increase in the number of CFU-S that survived immediately after irradiation. Also, 7 months after irradiation, the number of CFU-S per femur of both saline- and rIL-1-injected mice was still less than 50% of normal values. Data in this report demonstrate that a single injection of rIL-1 prior to irradiation accelerates early hematopoietic recovery in irradiated mice, but does not prevent expression of radiation-induced frontend damage or long-term damage to hematopoietic tissues.

Animals↗
PubMed1987

Glucan: mechanisms involved in its "radioprotective" effect.

It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested.

5'-Nucleotidase↗
PubMed1987

Enhanced hematopoietic recovery in irradiated mice pretreated with interleukin-1 (IL-1).

Data in this report compare the number of colony-forming cells (CFC) in bone marrow from irradiated and pre-irradiated C57Bl/6J mice injected with saline or recombinant interleukin-1-alpha (rIL-1). Eight to 12 days after sublethal or lethal irradiation, there were more CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units erythroid), GM-CFC (granulocyte-macrophage colony-forming cells), and day 8 CFU-S (colony-forming units-spleen) in bone marrow from rIL-1 injected mice than from saline injected mice. Prior to irradiation, there was no increase in number of CFC in bone marrow from rIL-1 injected mice. However, as determined by sensitivity to hydroxyurea, rIL-1 injection stimulated GM-CFC into cell cycle. These results demonstrate that rIL-1 injection increases the number of CFC that survive in irradiated mice and may be a consequence of the stimulation of CFC into cell cycle prior to irradiation.

Animals↗
PubMed1986

A comparative evaluation of particulate and soluble glucan in an endotoxin model.

Particulate glucan (P) but not soluble glucan (F) has been shown to sensitize rats to endotoxins. This phenomenon is believed to be mediated by the reticuloendothelial system (RES). The effect of glucan-P and -F on the RES, and the response of glucan-treated rats to nonlethal doses of endotoxin were investigated. Rats were injected for 5 days with 10 mg/kg of glucan-P, -F or saline. Three days later rats were either (1) injected with colloidal carbon for clearance studies, (2) sacrificed for organ histology and determination of serum glucose, plasma thromboxane (Tx) B2, and plasma 6-keto-prostaglandin (PG) F1 alpha concentrations, or (3) challenged with a nonlethal dose of endotoxin. The latter were further subdivided into groups for either 30-day survival or for sacrifice at 30 min or 4 h post-endotoxin infusion to obtain blood samples for glucose, TxB2, and 6-keto-PGE1 alpha determinations. Glucan-P induced hepatosplenomegaly and granulomatous changes within the liver and spleen. The carbon clearance halftime was markedly decreased in these animals. In glucan-P-treated rats challenged with endotoxin, elevated concentrations of both plasma prostanoids were observed as well as alterations in serum glucose levels. These changes were less pronounced in glucan-F- or saline- treated rats. Following endotoxin challenge, only 40% of glucan-P-treated rats survived 30 days whereas 100% of both the glucan-F and saline-treated rats survived. We conclude that glucan-P, in contrast to glucan-F, significantly heightens RES function and that this effect likely accounts for the endotoxin sensitivity.

Animals↗
PubMed1986

The rhesus monkey: a primate model for hemopoietic stem cell studies.

Two heterogeneous cell populations (CP 1-7 and CP 8-10) were separated from rhesus monkey bone marrow using counterflow centrifugation-elutriation (CCE). These two cell populations were distinct with respect to morphological composition, expression of cell surface antigens, hemopoietic progenitor cell activity, and concentration of hemopoietic stem cells (HSC). The hemopoietic progenitor cell activity and HSC were concentrated in CP 8-10. In autologous transplantation studies, CP 8-10 reconstituted the lymphohemopoietic system of lethally irradiated monkeys in a manner similar to that of monkeys transplanted with unfractionated bone marrow cells. CP 1-7 was lymphocyte rich and depleted of progenitor cell activity. Transplantation of CP 1-7 led to eventual lymphohemopoietic reconstitution of irradiated monkeys; however, complete engraftment was delayed by as much as 14 days compared to either the transplantation of CP 8-10 or to unfractionated bone marrow. Thus, a presence of the HSC in the lymphocyte-rich progenitor-cell-depleted population can be detected in the rhesus model.

Animals↗
PubMed1986

Radioprotective properties of detoxified lipid A from Salmonella minnesota R595.

In the past, the toxicity of bacterial lipopolysaccharide (LPS) or its principal bioactive component, lipid A, has detracted from their potential use as radioprotectants. Recently, a relatively nontoxic monophosphoryl Lipid A (LAM) that retains many of the immunobiologic properties of LPS has been isolated from a polysaccharide deficient Re mutant strain of Salmonella minnesota (R595). The ability of the native endotoxic glycolipid (GL) from S. minnesota (R595) as well as diphosphoryl lipid A (LAD) and nontoxic monophosphoryl lipid A (LAM) derived from GL to protect LPS responsive (CD2F1 or C3H/HeN) and nonresponsive (C3H/HeJ) mice from 60Co gamma irradiation has been studied. Administration of GL, LAD, or LAM to CD2F1 or C3H/HeN mice (400 micrograms/kg) 24 h prior to exposure provided significant radioprotection. No protection was afforded to C3H/HeJ mice. Experiments were also conducted to determine the relative abilities of GL, LAD, and LAM to stimulate hematopoiesis as reflected by the endogenous spleen colony (E-CFU) assay. Protection was not correlated with the ability of these substances to increase E-CFUs or to induce colony-stimulating activity (CSA).

Animals↗
PubMed1986

Glucan-induced hemopoietic and immune stimulation: therapeutic effects in sublethally and lethally irradiated mice.

The hemopoietic effects of glucan, a beta 1,3 polyglycan biological response modifier, were assayed in normal and irradiated mice. In normal mice, glucan administration increased the content of bone marrow and splenic transplantable pluripotent hemopoietic stem cells (CFU-s), committed granulocyte-macrophage progenitor cells (GM-CFC), and pure macrophage progenitor cells (M-CFC). In mice partially hemopoietic depleted by exposure to 6.5 Gy of 60Co irradiation glucan increased the number of endogenous pluripotent hemopoietic stem cells (E-CFU). The most pronounced effects were observed when glucan was administered 1 day before irradiation. In addition, the administration of glucan 1 day before lethal (9.0 Gy) irradiation-enhanced survival. The enhanced survival in glucan-treated mice in part appeared to be mediated by an enhanced resistance to the surgence of enteric opportunistic pathogens that occurs following radiation-induced hemopoietic and immune depression.

Adjuvants, Immunologic↗
PubMed1986

Hemopoietic effects of intravenous soluble glucan administration.

A soluble form of the reticuloendothelial- and immune modulating agent glucan (glucan-F) has been evaluated for its effects on hemopoiesis. A single 5.0 mg intravenous injection of glucan-F into C3H/HeN mice increased peripheral white blood cellularity, bone marrow and splenic cellularity, bone marrow and splenic granulocyte-macrophage progenitor cell numbers (GM-CFC), and splenic pluripotent stem cell (CFU-s) and erythroid progenitor cell (CFU-e) numbers. Serum levels of granulocyte-macrophage colony stimulating activity (CSA) were also elevated following glucan-F administration. These hemopoietic responses correlate well with those previously shown to be induced by intravenous administration of particulate glucan (glucan-P). In contrast to glucan-P, however, intravenous glucan-F administration has been shown not to induce granuloma formation and severe hepatosplenomegaly, thus the potential clinical use of glucan-F as a hemopoietic stimulant is more likely than that of glucan-P.

Animals↗
PubMed1986

Comparative effects of soluble and particulate glucans on survival in irradiated mice.

The survival-enhancing capabilities of particulate (P) and soluble (F) glucan, a B-1,3 polyglycan biological response modifier, were assayed in 60Co irradiated mice. Although glucan-P was slightly more effective than glucan-F, both glucans significantly enhanced survival in otherwise lethally irradiated (9.0-11.0 Gy) C3H/HeN mice. Following 9.0 Gy, 60% of the glucan-P treated and 53% of the glucan-F treated mice exhibited long-term survival as opposed to 0% of the radiation control mice. The survival-enhancing effects of glucan-P and glucan-F decreased as the radiation dose increased to 11.0 Gy. At higher radiation doses (e.g., 12.0 Gy) neither glucan preparation was capable of enhancing survival. Both glucan-P and glucan-F enhanced the recovery of peripheral blood white cell numbers, platelet numbers, and hematocrit values. In addition, both agents increased endogenous pluripotent hemopoietic stem cell numbers in sublethally irradiated mice. Taken together, these results demonstrate that both glucan-P and glucan-F can significantly enhance survival in lethally irradiated mice. However, these agents appear to function specifically by enhancing hemopoietic recovery and are not effective at radiation does also known to induce gastrointestinal damage.

Animals↗
PubMed1985

Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice.

Hemopoietic effects of the reticuloendothelial agent glucan were assayed in normal mice and in mice hemopoietically depleted by exposure to 60Co radiation. In normal mice, glucan administration increased the content of bone marrow and splenic transplantable pluripotent hemopoietic stem cells (CFU-s), committed granulocyte-macrophage progenitor cells (GM-CFC), and pure macrophage progenitor cells (M-CFC). Erythroid progenitor cells (CFU-e) were increased only in the spleen. In sublethally irradiated mice (650 rads), glucan increased the number of endogenous pluripotent hemopoietic stem cells (E-CFU) when administered either before or after irradiation. The most pronounced effects were observed when glucan was administered 1 day before, 1 h before, or 1 h after irradiation. In addition, the administration of glucan before lethal irradiation (900 rads) enhanced survival. The most significant results were seen when glucan was administered 1 day prior to irradiation. The possibility of using agents such as glucan to enhance hemopoietic reconstitution and prevent septicemia following chemotherapy and/or radiotherapy is discussed.

Adjuvants, Immunologic↗
PubMed1984

Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells.

Glucan, a beta-1,3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistently exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage, and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.

Animals↗
PubMed1984

Soluble polyglycans enhance recovery from cobalt-60--induced hemopoietic injury.

Six soluble polyglycans (glucan-C, glucan-F, glucan-S, krestin, lentinan, and schizophyllan), two soluble polymannans (mannan-A and mannan-R), and one soluble polyfructan (levan) were assayed for their ability to enhance hemopoietic recovery in C3H/HeN mice when administered either 1 h before or 1 h after a 6.5-Gy dose of cobalt-60 radiation. Hemopoietic recovery was measured by the endogenous spleen colony assay and was compared with recovery in both radiation control mice and irradiated mice treated with glucan-P (a particulate polyglycan previously shown to enhance recovery from radiation-induced hemopoietic injury). Compared with radiation controls, when administered before irradiation, mannan-A, glucan-F, and glucan-S enhanced endogenous colony formation 4.2-5.1-fold (equivalent to glucan-P), and levan and schizophyllan approximately 2.7-fold. Lentinan, krestin, mannan-R, and glucan-C did not enhance hemopoietic recovery above radiation controls under these conditions. When polyglycan administration was delayed until after irradiation, endogenous colony formation was enhanced 3.0-3.9-fold by mannan-A, schizophyllan, glucan-S, krestin, and glucan-F (at least comparable with glucan-P) but not at all by mannan-R, levan, lentinan, or glucan-C.

Animals↗
PubMed1983

Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of the immunomodulating agent glucan.

The hemopoietic effects produced by six different doses of a commercially available glucan preparation were investigated. C3H/HeN mice were intravenously injected with either 0.1, 0.4, 0.8, 1.2, 1.6, or 2.0 mg of glucan. Five days later, total nucleated cellularity, pluripotent stem cells (CFU-s), granulocyte-macrophage colony-forming cells (GM-CFC), macrophage colony-forming cells (M-CFC), and erythroid burst- and colony-forming cells (BFU-e and CFU-e) were assayed in the bone marrow and spleen. Neither femoral cellularity nor GM-CFC content was altered by any of the glucan doses tested. By contrast, bone marrow CFU-s content increased and CFU-e and BFU-e contents decreased with increasing glucan doses. In the spleen, all aspects of hemopoiesis (i.e., cellularity, CFU-s, GM-CFC, M-CFC, and CFU-e) increased after glucan administration. The degree of splenic enhancement was directly correlated with the dose of glucan administered.

Adjuvants, Immunologic↗
PubMed1983

Temporal response of murine pluripotent stem cells and myeloid and erythroid progenitor cells to low-dose glucan treatment.

B6D2F1 female mice were intravenously administered 0.4 mg of glucan. 1, 5, 11, and 17 days later, the total nucleated cellularity (TNC) and the numbers of pluripotent hemopoietic stem cells (CFU-s), granulocyte-macrophage progenitor cells (GM-CFC), and erythroid colony-forming (CFU-e) and burst-forming (BFU-e) cells were assayed in the bone marrow and spleen. Bone marrow TNC was not altered, but splenic TNC increased approximately twofold on day 5 and remained increased on days 11 and 17 after glucan treatment. The concentrations of bone marrow and splenic CFU-s and GM-CFC both significantly increased (p less than 0.01) by 5 days after glucan administration; however, they returned to control levels by day 17. Splenic CFU-e concentration increased on days 5, 11, and 17, whereas splenic BFU-e concentration increased only on day 11 after treatment. By contrast, bone marrow CFU-e and BFU-e concentrations were either unaffected or slightly decreased by glucan treatment. When peripheral blood was assayed for CFU-s and GM-CFC, no detectable increase in the concentrations of these progenitors was noted at any time after glucan treatment. The relevance of these effects of low-dose (0.4 mg) glucan treatment is discussed with respect to previously reported effects of higher-dose (e.g., 4.0 mg) glucan treatment.

Animals↗