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)

The number and distribution patterns of lymphocytes in the spleens and lymph nodes of Balb/c mice which express immunoglobulin surface receptors were studied in terms of the effects of a murine leukemia virus on the immune-response mechanism. Friend leukemia virus induces a prompt, marked depression of the immune response of mice to antigens such as sheep erythrocytes and E. coli LPS. A functioning T- and B-lymphocyte system is necessary for the response to the SRBC's whereas E. coli LPS, a T cell-independent antigen, stimulates B cells alone. Although the responses to both classes of antigen were markedly depressed in FLV-infected mice, the major defect appeared to be impairment of B-cell function, at least early in the course of infection. In order to examine in more detail the mechanism of interaction between FLV and lymphoid cells with Ig surface receptors, presumably B cells, immmunofluorescent analyses were performed with spleen, and lymph node cells from FLV-infected mice. Within a few days after infection there was a marked decrease in the percentage of spleen cells with Ig surface molecules, although the absolute number of these cells was either unchanged or increased due to marked splenomegaly caused by the virus. A marked decrease in the percentage of splenocytes with theta antigen, considered a marker for mature T cells, also was evident in infected mice. The number of spleen cells showing evidence of FLV infection (i.e., positive for FLV-associated antigens) increased rapidly during the first few days after infection, and within 2 to 2 1/2 weeks nearly all of the nucleated splenocytes were positive for the tumor antigen. In contrast to the results for spleen cells, there were increases rather than decreases in the percentages of Ig-positive and theta-positive cells in the lymph nodes after infection. The number of lymph-node cells that showed the presence of FLV antigen was much lower than in the spleen, and their appearance was also much slower as the leukemic process progressed. Despite these differences between spleen and lymph-node cells in terms of relative percentages of Ig- and theta-positive lymphocytes, relatively similar depressions were evident for the percentages of lymphoid cells that could redistribute their surface Ig receptors into polar caps when incubated with anti-Ig serum at 37 C. Marked impairment of the Ig-capping responses for both spleen and lymph-node cells paralleled the course of infection and development of immunosuppression. These observations indicate that murine leukemia virus infection can both alter the responsiveness of immunocompetent cells to T-dependent and independent antigens and depress the number and normal functional activity of these cells, as reflected by altered surface Ig receptors and antigens.
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PMID:Lymphocyte surface receptors and leukemia virus-induced immunosuppression. 109 86

Active human serum manifests a tumoricide effect against cells of the Ehrlich ascites tumor. Sera of patients with Ca ventriculi show a higher effect than those of patients with a chronic streptococcal disorder, in comparison with intact subjects. This tumorcide effect is depressed by Varidase, the degree of depression being greatest in the group of patients with streptococcal infection, smaller in healthy subjects and least in carcinoma patients. The investigated sera contained antibodies against Varidase, but not against streptokinase. The anti-Varidase antibodies are found also in sera of the new-born children. The decline of the tumoricide activity of Varidase-treated sera is related to the quantity of anti-Varidase antibodies determined by complement fixing reaction in non-treated sera.
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PMID:Lowering of the tumoricide activity of human serum with Varidase. II. Antibodies against Varidase in human serum measured by complement binding. 109 70

An initial clinical phase I trial of inosine dialdehyde has been carried out in 40 patients at dose levels of 30-4000 mg/m2 for 5 days given intravenously (iv) monthly. At 1.5 g/m2, noncumulative dose-related toxicity occurred in all patients which consisted of nausea and vomiting, local pain, alterations in coagulation mechanism, elevated partial thromboplastin time, and positive Coombs' test. No dose-limiting leukopenia, thrombocytopenia, anemia, or bleeding occurred; however, depression of the leukocyte and platelet counts, and decreased hemoglobin value were observed. The dose-limiting toxic effect was renal tubular damage with reversible acute renal failure in one of four patients who received 3000 mg/m2 iv for 5 days. Refractory hypercalcemia was controlled in three of three patients without tumor effect. Responses occurred in patients with seminoma, oat cell carcinoma, and melanoma. A starting dose of 2 g/m2 for 3 days monthly is recommended for phase II trials and a trial in lung carcinoma is now being conducted.
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PMID:Clinical phase I trial of inosine dialdehyde (NSC-118994). 110 41

Pentobarbital depressed macromolecular synthesis in Ehrlich ascites cells in vitro, and this depression was proportional to a decrease in oxygen consumption. However, survival time of animals bearing Ehrlich ascites cells was unaffected by pentobarbital. The acute toxicity of the drug was greatly enhanced by the presence of the tumor. Sleeping time was prolonged in mice carrying the following tumors: Ehrlich ascites, Sarcoma 180 ascites, and Yancy plasma cell solid. Seven-day Ehrlich ascites tumor-bearing animals treated with pentobarbital slept about three times longer than normal mice, but both groups awoke at the same plasma levels of the unbound drug. The plasma half-life of unchanged pentobarbital was about four times as long in tumor-bearing mice as it was in controls. No qualitative difference in catabolism other than rate was detected. Renal excretion of unchanged pentobarbital in tumor-bearing animals was 50% of control animals during the first 4 hr. In tumor-bearing mice the sleeping time of the nonmetabo ble barbiturate, barbital, was identical with that in normal animals. These data suggest that the tumor affected mainly pentobarbital metabolism. Tumor-bearing mice still responded to the pharmacological challenge of phenobarbital with the apparent induction of drug metabolizing enzymes. The prolonged pentobarbital sleeping time in tumor-bearing mice required the development of some type of tumor-host relationship.
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PMID:Physiological disposition of pentobarbital in tumor-bearing mice. 112 Mar 16

An increase in prostaglandins (PGs) of the E series has been demonstrated in Moloney sarcoma virus (MSV)-induced leg tumors of 6-week-old BALB/c male mice. The level of the hormone has been shown to increase with the tumor diameter and decrease with tumor regression. At the peak of tumor size the tibial bones of the mice were considerably deformed, suggesting osteoclastic activity. The systemic calcium level was not elevated, indicating possible release of calcium into the local tumorous area. In mice treated with indomethacin the tumors failed to develop and PG levels were markedly lower. Tibial bones of treated mice were similar in appearance to those of control, non-tumorous mice. PG levels of DBA/1J mice bearing extensive Cloudaman S91 melanomas were not elevated and no bone deformation was seen. When contrasted with studies of immuno-depressed mice the results suggest that indomethacin acted in conjunction with and possibly to restore the PG-induced depression of the immune system in preventing tumor development. It is also hypothesized that indomethacin, by suppressing the PG-mediated calcium release from bone, could be operative in inhibiting tumor growth.
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PMID:Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in balb/c mice. 114 Aug 69

Events preceeding the cortisol inhibition of uridine utilization by corticoid-sensitive P1798 lymphocytes have been investigated. When tumor cells were incubated with 1 muM cortisol for 15 min and then washed free of steroid and reincubated in the absence of hormone, the expected decrease of uridine uptake failed to appear 1.5 hr later. In contrast, the removal of cortisol after 30 or 60 min did not prevent subsequent development of the steroid effect. Addition of actinomycin D with cortisol, or 15 min after hormone treatment was started, blocked steroid action. However, when actinomycin D was added 30 or 60 min after the initial exposure to cortisol, hormone-induced depression of uridine uptake was no longer prevented. To study the role of protein synthesis, cycloheximide was added to the tumor cell suspensions at various times after cortisol treatment was started. Cortisol suppression of uridine utilization was blocked when cycloheximide was added with the hormone or 30 min after the start of hormone treatment. Cycloheximide added together with cortisol and washed out with the steroid after 30 min did not prevent subsequent appearance of decreased nucleoside uptake. Hydroxyurea, an inhibitor of DNA synthesis, did not prevent cortisol action, even when present throughout a 2 hr exposure to the steroid. Hormone removal or actinomycin D addition after 1.5 to 2 hr (when uridine uptake was already inhibited about 25%) did not prevent intensification of the steroid effect during a subsequent 1.5- to 2-hr incubation period, while addition of cycloheximide at this time completely prevented its progression. These results suggest aht: (a) cortisol inhibition of uridine uptake by P1798 lymphocytes involves an early irreversible step and appears to require continuing RNA but not protein synthesis during the first 15 to 30 min of hormone action; (b) protein synthesis but not RNA synthesis is required between 30 and 60 min; and (c) continuing protein synthesis but not RNA synthesis or hormone presence is necessary for the preestablished cortisol effect to progress.
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PMID:Sequential irreversible, actinomycin D-sensitive, and cycloheximide-sensitive steps prior to cortisol inhibition of uridine utilization by P1798 tumor lymphocytes. 114 29

The effect of certain disease parameters on remission and survial time was evaluated in 482 patients with multiple myeloma treated with intermittent courses of melphalan-prednisone combinations. Increasing degrees of anemia, hypercalcemia, azotemia, and high serum myeloma protein levels were associated with progressive lifespan shortening. The short survival of patients with anemia and hypercalcemia was associated with short remissions in responding patients with these abnormalities. The extent of tumor mass was defined from specific laboratory parameters reported by Durie to be associated with large numbers of plasma cells. More advanced stages of myeloma were associated with higher frequencies and degrees of normal immunoglobulin depression. The response rate was not affected by the tumor mass grade, but increasing tumor mass was associated with a shorter lifespan. Greater degrees of tumor reduction were associated with longer remission and survival times. Patients in whom a marked tumor reduction was rapid had shorter survival and remission times than patients who responded more slowly.
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PMID:Prognostic factors in multiple myeloma. 117 23

The systematic chemical control of cancer requires a quantitative knowledge of the pharmacologic disposition of antitumor drugs in both healthy and malignant tissues in the body. Pharmacokinetic models can predict the drug concentration in both tumor sites and healthy organs and hence may provide a predictive capability regarding both antitumor action and concomitant toxicity. Adriamycin is an anthracycline antibiotic that has been demonstrated to possess a broad spectrum of antitticularly solid tumors. Its major toxicity is manifested by the depression of normal cell proliferation in the bone marrow and a delayed dose-dependent cardiac toxicity eventually resulting in congestive heart failure. This study is concerned with the development of a predictve analytic model for the pharmacokinetics of adriamycin. The analytic approach embodies a physiologic multicompartmental model as a framework. This model postulates that specific organs or tissue masses may be simulated by a compartment whose elements consist of physiologic properties such as tissue volume and blood flow and pharmacologic behavior such as tissue binding and metabolic activity. A mass balance is set up across each compartment and all compartments are linked by an independent blood compartment. The mass balance includes terms representing inflow and outflow of the drug as well as its metabolism, protein-binding, and other pharmacologic behavior. A model has been developed that has ten compartments which represent the plasma, heart, liver, kidney, lung, lean tissue, adipose tissue, gut, bone marrow, and spleen. Solutions of the system of equations yield the time course of the drug in each organ. Predictions of adriamycin concentration-time curves in the ten tissues after intravenous (iv) administration were generated using this model. With few exceptions, agreement between predicted and actual tissue data in rabbits was excellent. Human plasma levels of adriamycin were predicted and comparison with patient data demonstrated a reasonable first approximation.
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PMID:Preliminary pharmacokinetic model for adriamycin (NSC-123127). 117 72

The potent skin tumor promoter (12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates epidermal macromolecular synthesis as well as proliferation, but little is known of specific functional aberrations produced by TPA. This report presents results of a study on the effects of TPA on epidermal histidase (L-histidine ammonia lyase), an enzyme found in normal epidermis but not in dermis or in mouse squamous cell carcinomas. Histidase activity was assayed on postmitochondrial supernatants obtained from hairless mouse epidermis after removal by keratotome. Topical TPA treatment at doses active in tumor promotion (1.7 to 17.0 nmoles/application) produced dose-dependent decreases in epidermal histidase specific activity at 19 hr posttreatment. The onset of the decrease occurred at 12 hr with recovery to control level specific activity by 5 days, showing kinetics similar to those obtained for stimulation of DNA synthesis. This decrease in histidase could not be attributed to a general inhibition of soluble protein synthesis or to the appearance of an inhibitor of histidase activity. The strong promoter TPA produced a greater histidase decrease than did the moderate promoter and mitogen 12,13-didecanoyl phorbol at equimolar dose, while phorbol, a nonpromoter and nonmitogen, produced no effects on histidase. The relationship of this histidase depression to tumor promotion and not initiation is further indicated by the finding that (a) Tween 60, a structurally unrelated tumor promotor, also produced a decrease in histidase; and (b) the tumor initiator urethan and an initiating dose of 9,10-dimethybenz(a)anthracene showed no effects on histadase activity.
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PMID:Decrease of epidermal histidase activity by tumor-promoting phorbol esters. 118 5

Previous studies from this laboratory indicated that inorganic and organic anions inhibit the unidirectional influx and net transport of the folate analog methotrexate in mammalian cells. Studies were undertaken to establish whether anions retained in uremia might inhibit the membrane transport of folates. Methotrexate was utilized as a model folate compound and its transport was determined in the Ehrlich ascites tumor cell. Influx of methotrexate was inhibited when cells were suspended into sera or ultrafiltrates of sera (pH adjusted to 7.4 by regulation of PCO2) from uremic patients, an effect that was decreased after the patient underwent hemodialysis or peritoneal dialysis. The inhibitory effect of uremic sera correlated well with the level of retained anions as estimated from the "anion gap," but could not be related to changes in osmolality, blood urea nitrogen (BUN), sodium, potassium, calcium, or magnesium. While inhibiting the influx of methotrexate, inorganic anions did not displace methotrexate from albumin binding sites. Anionic inhibition of the membrane transport of 5-methyl [14C] tetrahydrofolate was also demonstrated and this was shown to be accompanied by a depression in the rate of incorporation of the labeled 14C moiety into nucleic acids and protein. The data suggested that transport of folates is impaired in uremia and raises the possibility that whatever the measured blood folate level in the uremic individual with retained anions, the rate of uptake of folates into folate-dependent tissues which this blood folate level will sustain may be reduced.
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PMID:Inhibition of the membrane transport of folates by anions retained in uremia. 118 41


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