Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rabbits were treated with cyclophosphamide and 5-fluorouracil, myelosuppressive cytostatic agents, applied with a single dose of 1/3 LD50 or daily doses of 1/30 LD50 given for 14 days. Functional tests for evaluation of granulopoiesis were regularly performed at standard intervals and were following: leukocytosis, bone marrow picture with mitotic index, 3H-thymidine incorporation in vitro followed by autoradiography of labeled promyelocytes and myelocytes, serum lysozyme activity, mobilization of granulocyte reserve pool by staphylococcal alpha-toxin, cytochemistry of granulocytes, phagocytosis ability and Nitro-BT reduction. It has been found that 6-10 days after application of cytostatics, a marked depression of proliferation of young granulocyte forms and lowered reserve pool, are regularly observed. This was followed by spontaneous regeneration of granulopoiesis. No changes were noted in functional tests of mature granulocytes in peripheral blood. It is suggested that for investigation of the impairment of granulopoiesis after application of cytostatic agents, most suitable is evaluation of mobilization of the bone marrow reserve pool, lysozyme activity in blood serum and labelling of promyelocytes and myelocytes with 3H-thymidine in vitro.
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PMID:Inhibition of normal granulopoiesis by cytostatic agents. 6 8

Pieces of human psoriatic skin and suspensions of mouse bone marrow cells as non-epidermal control tissue were cultured for four days in diffusion chambers implanted intraperitoneally in 40 mice. The mice were divided into three groups. On the second and third day of the culture partially purified epidermal extract containing epidermal chalone, granulocyte extract containing granulocyte chalone, and Hanks' solution were injected intraperitoneally into the mice of the three groups, respectively. On the fourth day, incorporation of 3H-TdR into the diffusion chamber cultures and various epithelia and several non-epidermal tissues of the host animal was studied autoradiographically and radiochemically. The results showed that the epidermal chalone induced a marked, statistically significant, depression in the labelling index of the cultured psoriatic epidermal cells and in the number of labelled cells in the host ear epidermis (31% and 62%, respectively); the other host epithelia were not significantly inhibited. A crude granulocyte extract used in most experiments was clearly toxic; the semipurified granulocyte chalone used in one experiment had no effect on the psoriatic and cultures, but affected weakly the cultured bone marrow cells. Neither the epidermal nor the granulocyte extract had any inhibitory effect on the non-epidermal tissues studied.
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PMID:Chalone-induced inhibition in DNA synthesis of human psoriatic epidermal cells cultured in diffusion chambers in mice. 13 22

In vitro studies have been done on haematopoietic cells from a patient with cyclic neutropenia characterized by severe depression of blood neutrophil levels every 21 days. Serial blood counts reveal periodic fluctuations in neutrophils, monocytes and reticulocytes. Agar culture of marrow cells shows normal concentration of colony forming cells. The percentage of colony forming cells in S phase is highly increased during profound neutropenia and normal during the recovery phase relating the granulocyte production to the peripheral neutrophil level. Studies of ingestion rate, bactericidal activity, lactate production and glucose oxidation during phagocytosis in isolated granulocytes show normal results. Also the ingestion rate in isolated monocytes is normal. Serial karyotype analyses of marrow cells during the neutrophil cycle display a normal pattern. Serum myeloperoxidase levels vary inversely with the peripheral neutrophil count indicating increased granulopoietic activity during profound neutropenia, which might be associated with non effective granulopoiesis during profound neutropenia, leading to a lack of granulocyte reserves in the marrow.
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PMID:Cell production and cell function in human cyclic neutropenia. 17 16

There is considerable evidence to suggest that macrophages participate in host resistance to the development and spread of cancer. We have, therefore, studied monocytemacrophage function in humans and animals with neoplasms. Approximately 60% of patients with various types of cancer were found to have abnormal monocyte chemotactic responsiveness in vitro, and abnormal chemotaxis was an indicator of poor prognosis in patients with melanoma. By studying patients before and after surgery, it was found that abnormal chemotactic responses normalized within weeks after removal of malignant tumors, indicating that a neoplasm itself might affect the host's monocyte chemotactic responsiveness. Subsequent studies using transplantable neoplasms in mice substantiated this hypothesis in that macrophage accumulation in vivo as well as macrophage chemotactic responsiveness in vitro was depressed in animals during the early phases of tumor growth. This depression of macrophage function could be attributed to a low-molecular-weight factor contained in murine neoplasms, which when given to normal mice was extremely potent in depressing peritoneal macrophage accumulation and chemotaxis but, paradoxically, enhanced phagocytosis. The serum of tumor-bearing mice also contained potent inhibitory activity for macrophage accumulation. In contrast to the effects on macrophages, granulocyte accumulation in vivo and chemotaxis in vitro was not depressed by the presence of a neoplasm or the administration of the factor from neoplasms. By releasing factors which depress macrophage migratory function, neoplasms may protect themselves from immunologically mediated host destruction during the early phases of tumor growth.
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PMID:Macrophage migratory dysfunction in cancer. A mechanism for subversion of surveillance. 19 6

Patients receiving cytotoxic drugs are at an increased risk of bacterial infection. Drug-induced leukopenia may be responsible for depression of host defenses; however, there is little information concerning the qualitative effects, if any, of cytotoxic agents on granulocyte antibacterial activity. Since methotrexate is now being used in massive doses in vivo, we investigated the effects of this drug on antibacterial and metabolic functions of normal polymorphonuclear leukocytes in vitro. Phagocytosis, quantitative protein iodination, and staphylococcal killing of normal polymorphonuclear leukocytes were found to decrease with exposure to increasing concentrations of methotrexate. The effects of methotrexate on these cell functions were rapid in onset and readily reversed by washing the cells, suggesting a locus of action on the cell membrane rather than at the level of nucleic acid synthesis. Exposure of cells to similar concentrations of folic acid or folinic acid produced no impairment of bacterial phagocytosis, suggesting that the observed effects are specific for methotrexate. The concentrations of methotrexate that produced these impairments are readily achieved in vivo and may alter antibacterial defenses in patients receiving this therapy.
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PMID:Inhibition of human granulocyte function by methotrexate. 30 60

A single injection of endotoxin, 4 hours after administration of 150 mg/kg of 5-fluorouracil (5-FU), stimulated the recovery of bone marrow hemopoietic cells that form colonies in spleen (CFU-S) or in culture (GM-CFC), of erythropoiesis, and of platelet production. Corynebacterium parvum injections had similar effects. Endotoxin-free extracts of tissues (from pregnant mouse uterus, placenta, and embryo) which have a high content of the factor(s) capable of stimulating growth of GM-CFC in vitro also stimulated recovery of CFU-S and GM-CFC when given in single injections 4 hours after 5-FU. A striking effect of both endotoxin and tissue extracts was the acceleration of the regeneration of a particular subclass of granulocyte macrophage progenitors, those capable of forming large colonies (greater than 0.25 mm) in agar. The results indicate that recovery of hemopoiesis after depression by 5-FU can be stimulated not only by injection of bacterial products, but also by injection of endotoxin-free tissue extracts which contain high levels of hemopoietic regulators.
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PMID:Effects of endotoxin and extracts of pregnant mouse uterus on the recovery of hemopoiesis after 5-fluorouracil. 31 24

We have shown in in vivo experiments that hemoglobin interferes with the attraction of polymorphonuclear granulocytes into the peritoneal cavity of rats in response to a bacterial inoculum and thus permits bacterial growth. These findings are proportional to the intraperitoneal concentration of hemoglobin. In in vitro experiments the chemotactic response of human polymorphonuclear granulocytes to zymosan activated serum as well as E. coli bacterial factor is inhibited by hemoglobin. While hemoglobin added in a concentration of 4% to the chemotactic factor causes a significant depression of granulocyte chemotaxis concentrations of only 0.01% are sufficient to cause inhibition of chemotaxis when hemoglobin is added to the cell suspension. The spontaneous migration of the cells is not influenced in either experiment.
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PMID:Inhibition of granulocyte chemotaxis by hemoglobin in experimental peritonitis. 37 46

The Kveim reaction was studied in vivo in 50 patients with sarcoidosis. Commonwealth Serum Laboratories Kveim material and a new Danish Kveim material gave 14 and 8 positive reactions respectively, as well as 6 and 8 equivocal reactions. Forty-six of the patients were also tested in vitro for cell mediated immunity to the Danish Kveim material, using both the leucocyte migration agarose technique and the capillary technique. No significant migration inhibition or stimulation were found. A tuberculin skin test was performed in 49 of the patients, and in 45 a dinitrochlorobenzene sensitivity titer was determined. Both tests revealed a depression of the cell mediated immunity. The serum levels of immunoglobulins IgG, IgA, IgM, IgD, and IgE were determined. The serum of each patient was also examined to determine if organ-non-specific and granulocyte-specific antinuclear factors of IgG class, antibodies against native DNA, rheumatoid factor, mitochondrial antibodies, antibodies against thyroid cytoplasm, and parietal cell antibodies were present. IgG levels were above normal in 28 patients; IgE was above normal in 10 patients, 4 of whom were atopics or had an atopic disposition. Organ-non-specific antinuclear factors were present in 17 patients.
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PMID:Humoral and cellular immunity in sarcoidosis. 64 46

Studies were done of cell production by marrow in diffusion chambers implanted in the peritoneal cavity of rabbits subjected to various stimuli to hematopoiesis. In chambers in neutropenic hosts and in hosts injected with endotoxin, animals presumed to have an increased stimulus to granulopoiesis, there was increased production of granulocytes but there was also increased production of red cells. Although red cell production was decreased in chambers in polycythemic hosts, granulocyte production was not different from that in controls. Stimulation of erythropoiesis by erythropoietin injections or by exposure to hypoxia increased red cell production by marrow in the implanted diffusion chambers without diminishing granulopoiesis. Only in chambers in hosts made anemic by bleeding was there an increase in red cell production accompanied by a decrease in granulocyte production. In these anemic hosts induction of neutropenia led to an increase in granulopoiesis without any depression of erythropoiesis.
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PMID:Marrow culture in diffusion chambers in rabbits. II. Effect of competing demands for red cell and white cell production on cell growth. 64 17

Female rats were treated with several administration regimens of methylprednisolone, cobra venom anti-complementary factor, and cyclophosphamide in conjunction with polyvinyl sponge implantations. The effect of these drugs on host factors active against bacteria was evaluated with Staphylococcus aureus ATCC 25933, Escherichia coli K-12, and Pseudomonas aeruginosa CDC 7725. One of two implants in each animal was infected with 10(8) of one of the three bacteria, and bacterial and granulocyte content was determined in the infected and control sponges after 48 h. The single large dose of methylprednisolone decreased staphylococcal and E. coli clearance while promoting dissemination of P. aeruginosa. A low chronic dose of the steroid inhibited E. coli chemotaxis only. A higher dose of the steroid administered chronically interfered markedly with S. aureus and E. coli curtailment by the host while leading to enhanced dissemination of P. aeruginosa, accompanied by a precipitous decline in granulocytes. Results with cobra factor resembled the higher chronic dose of steroid enhancing, especially the dissemination of the pseudomonad and its anti-granulocytic propensity. Cyclophosphamide depression of granulocytes revealed the rat's ability to curtail the proliferation of particular S. aureus and E.coli strains even in the absence of leukocytes. This treatment resulted in the rapid spread of P. aeruginosa, leading to the death of some experimental animals. These experiments underline the versatility of this animal model in the study of host and microbial factors influential in infectious disease.
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PMID:Rat polyvinyl sponge model for the study of infections: host factors and microbial proliferation. 82 14


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