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)

Antitumor activity and bone marrow toxicity of a new nitrosourea analog, 1-(beta-D-glucopyranosyl)-3-(2-chloroethyl)-3-nitrosourea (GANU), were compared with those of 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose (Chlorozotocin) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). GANU was found to be highly active against mouse leukemia L-1210 when administered intraperitoneally or intravenously, being the same degree as Chlorozotocin. Even by oral route, GANU exhibited significant activities, whereas Chlorozotocin failed to show any activities by this route. Studies on the bone marrow toxicity as measured by the depression of white blood cell counts and the marrow cellularity revealed that both GANU and Chlorozotocin were less toxic than BCNU. GANU, however, weemed to be rather more toxic than Chlorotocin.
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PMID:Comparative studies on the antitumor activity and the bone marrow toxicity of 1-(beta-D-glucopyranosyl)-3-(2-chloroethyl)-3-nitrosourea and 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose. 89 99

The average concentration of orotic acid in the milk of 412 Black and White bred cows from four Polish provinces was 0.618 +/- 0.233 mmol/l. There was no correlation between milk yield and concentration of orotic acid. A higher concentration of this pyrimidine in younger cows, and its increase during development of lactation was noted. The yearly pattern of orotic acid in milk and urine of four low-, and four high-orotate cows was examined. In spite of high average differences in milk orotate (0.397 and 0.813 mmol/l) no significant differences in urinary orotate (20.96 and 21.90 mumol/mmol creatinine) were observed. In both groups the lowest milk orotate level occurred in early lactation. The orotic acid content (mmol/l) in commercial milk products was as follows: skim milk--0.783; evaporated milk--0.538; cream 12% fat--0.367; buttermilk--0.449; yogurt--0.331; kefir--0.341; sour milk 2% fat--0.360; dried skim milk--1.042; Bebiko I (infant formula)--0.650. Leukemia led to the elevation (0.845 mmol/l), whereas mastitis to the depression (0.124 mmol/l) of milk orotic acid level.
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PMID:Variability of orotic acid concentration in cow's milk. 195 38

Central nervous system regulation of endocrine functions is mediated by neurotransmitters, via hypothalamic hypophysiotropic factors which in turn control anterior pituitary functions. The evidence of serotonergic-endocrine interrelations with regard to adrenal, thyroid, gonadal and prolactin functions is fast accumulating. Our study extends the importance of those interrelations to some functions of the immune system. Multiple administration of 5-hydroxytryptamine(serotonin) or its precursor, 5-hydroxy-L-tryptophan(5-HTPH), produces marked depression of T cell dependent, humoral, hemolytic, primary immune response in mice. L-tryptophan, a more distant serotonin precursor, produces slight but significant depression of this immune response. Multiple treatment of mice infected with Friend Leukemia Virus (FLV) with serotonin or 5-HTPH alone or in combination with cyclophosphamide (Cytoxan) results in significant delay of the clinical progression of the infection. L-tryptophan produces a modest but significant improvement. Administration of serotonin or 5-HTPH causes a marked reduction of the thymus weight. It is reasonable to postulate that the described effects result from the thymus involution which affects the T cell compartment of the immune system. This is the consequence of hormonal imbalance caused by the alteration of the serotonin biosynthetic pathway in the brain. The adrenal cortex is not implicated in the mediation of this effect. Since many clinically used drugs affect the serotonin metabolism, the clinical consequences of the resulting alteration of the immunological responsiveness should be considered.
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PMID:Serotonin and its precursors as modulators of the immunological responsiveness in mice. 696 31

Patients with hairy cell leukemia (HCL) are susceptible to opportunistic intracellular infections, suggesting defects in cellular immunity. Prior studies have indicated an association between failure of IFN-alpha generation by peripheral blood mononuclear cells (MNC) and susceptibility to such infections. We here present results on IFN-alpha generation in HCL patients pre- and post-therapy. Prior to treatment with 2-chloro-2'-deoxyadenosine (CdA), MNC from 24 HCL patients with active disease produced little or not IFN-alpha (geometric mean < 40 IU/ml) compared with controls (n = 140, geometric mean 1730 IU/ml, p < 0.0005). After treatment with CdA, IFN-alpha generation was studied in 16 patients, with a geometric mean value of 650 IU/ml (p < 0.0005 compared with pre-CdA levels). The severe depression of IFN-alpha generation improved progressively following CdA therapy-induced clinical remission. We propose that deficiency of IFN-alpha production may play a role in the susceptibility to intracellular infections of patients with active HCL.
Leukemia 1994 Sep
PMID:Impaired interferon alpha response in hairy cell leukemia is corrected by therapy with 2-chloro-2'-deoxyadenosine: implications for susceptibility to opportunistic infections. 791 89

In solid tumors, p53 antibodies are found in 30% of the patients with p53 mutations, and their analysis is an interesting method for the detection of p53 mutations. We looked for circulating p53 antibodies in 83 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), by an ELISA technique. Detection of p53 mutations was made by single stranded conformation polymorphism (SSCP) analysis of exons 4 to 10 of the P53 gene and confirmed by direct sequencing. Circulating antibodies to p53 were seen in three of the 83 (3.5%) patients analyzed, and a p53 point mutation was found in ten cases. Two of the three patients with p53 antibodies had a p53 mutation, but the remaining case had no detectable mutation. The other eight mutated cases had no detectable p53 antibodies. Our findings show that serological analysis of p53 antibodies is rarely positive in MDS and AML. This could be due to the relatively low incidence of p53 mutations seen in those disorders, but also to the immune depression to which they are often associated.
Leukemia 1994 Sep
PMID:Detection of serum anti p53 antibodies and their correlation with p53 mutations in myelodysplastic syndromes and acute myeloid leukemia. 809 36

Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans and dog; substantial sex-related differences in skeletal plutonium retention and bone sarcoma induction in mice but not in humans or dog; and induction of head sinus carcinomas by 226Ra in humans but not the beagle. Leukemia and other related neoplasms were not induced in radionuclide-injected lifespan dogs in excess of the occurrence in control animals. Much of our current understanding of skeletal biology and radionuclide behavior in mammals was derived from this and related projects. The primary goal of the Utah experiment of estimating toxicities of bone-seeking radionuclides relative to radium has been accomplished. For 226Ra = 1.0, comparative toxicities (ratios) of a single injection for bone tumor induction in beagles were about 16 +/- 5 for monomeric 239Pu (32 +/- 10 for chronic exposure), 6 +/- 0.8 for 241Am, 8.5 +/- 2.3 for 228Th, 6 +/- 3 for 249Cf, 4 +/- 2 for 252Cf, 6 +/- 2 for 224Ra (16 +/- 5 for 50 weekly injections), 2 +/- 0.5 for 228Ra, and between 0.01 +/- 0.01 and 1.0 +/- 0.5 for 90Sr, depending on the dose-rate, with the lowest dose-rates approaching a ratio of zero. Corresponding ratios in mice for 226Ra = 1.0 were 16 +/- 4 for monomeric 239Pu, 5.4 +/- 2.0 for 224Ra (16 for 50 weekly injections), 4.9 +/- 1.4 for 241Am, 5.0 +/- 1.4 for 249Cf, 2.6 +/- 0.8 for 252Cf, 4.4 +/- 1.8 for 243,244Cm and about 1.0 for 90Sr at high doses, decreasing to near zero for low doses.
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PMID:Comparison of internal emitter radiobiology in animals and humans. 897 34

Thalidomide, an antiemetic administered in 60th of the 20th century to pregnant women, has become notorious for a range of adverse effects which led to its taking off market. In recent years, its antimyeloma effect was discovered. The aim of the work was to evaluate the incidence of adverse reactions to thalidomide. Its therapeutic effect has not been assessed because of a short period of monitoring and diversity of a sample. The assessed sample consisted of 17 patients with diagnosis of multiple myeloma (10 men and 7 women). An average age of patients was 62.9 +/- 9.4. An average time elapsed from making the diagnosis to starting the treatment with thalidomide was 51.0 +/- 23.7 months. An average length of therapy was 20.1 +/- 9.6 weeks. An average daily maximum therapeutic dose was 138.3 +/- 83.2 mg. Data were collected from outpatient physicians reports, regular laboratory tests, and direct interviews with patients. To classify severity of adverse drug effects (grades 0-4) we used WHO criteria, Cancer and Leukemia Group B criteria, and in cases where certain adverse effects were not included in the above mentioned criteria, we defined our own criteria. The most frequent adverse effects included: leucopenia or neutropenia in 12 (70.6%) patients, altered state of consciousness in 11 (64.7%) patients, obstipation in 10 (58.8%) patients, skin alterations in 9 (52.9%) patients, dizziness in 8 (47.1%) patients, peripheral neuropathy in 7 (41.2%) patients, spasms and spasmodic convulsions in 7 (41.2%) patients, and altered liver tests in 6 (35.3%) patients. From the perspective of necessity to interrupt treatment or reduce the dose the most severe disorders included: peripheral neuropathy in 2 patients (inability to control lower extremities), altered consciousness in 1 patient (protracted somnolence during a day), skin alteration in 1 patient (generalized toxoalergic reaction), leucopenia or neutropenia in 1 patient (1.0 resp < 0.5 x 10(9)/l), altered vision in 1 patient (blurred vision), hypothyroidism in 1 patient, and altered mood in 1 patient (subjective feeling of depression). This work proved thalidomide to be beneficial for the patients with multiple myeloma but it also shoved necessity to intensively monitor its adverse effects and to adjust its doses.
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PMID:[Desirable and undesirable effects of thalidomide in patients with multiple myeloma]. 1468 82

We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.
Leukemia 2005 Sep
PMID:A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors. 1599 Aug 68

Extracts of the plant St John's wort, Hyperforin perforatum L., have been used for centuries in traditional medicine, notably for the treatment of depression. One of their main lipophilic components, a natural prenylated phloroglucinol termed hyperforin (HF), has been identified as the major molecule responsible for the antidepressant effects of this plant. Within the last few years, a number of studies have demonstrated that HF displays, in addition, several other biological properties of potential pharmacological interest. They include an antibacterial capacity and inhibitory effects on inflammatory mediators. It is worth noting that HF also promotes apoptosis of various cancer cells from solid tumors and hematological malignancies, including B-cell chronic lymphocytic leukemia. In addition, HF inhibits the capacity of migration and invasion of different tumor cells, as well as exhibiting antiangiogenic effects. Altogether, these properties qualify HF as a lead structure for the development of new therapeutic molecules in the treatment of various diseases, including some malignant tumors.
Leukemia 2006 Sep
PMID:Hyperforin, a new lead compound against the progression of cancer and leukemia? 1679 Dec 62

Multidrug resistance of neoplastic tissue is often associated with the overexpression and increased drug transport activity of plasma membrane transporters like P-glycoprotein (P-gp), multidrug resistance associated proteins (MRPs) or breast cancer resistance protein, as well as with the elevation of the glutathione detoxification pathway. We have already described the overexpression of P-gp under the selection pressure of vincristine in L1210 mouse leukemia cells. In the present study, mechanisms of multidrug resistance induced in L1210 cells cultivated in the presence of doxorubicin were analyzed. The selection pressure of both vincristine (yielding a resistant subline of L1210 cells, R(V)) and doxorubicin (yielding a resistant subline of L1210 cells, R(D)) induced a dramatic depression of cell sensitivity to both drugs. Both R(V) and R(D) cells demonstrated a lack of ability to accumulate calcein/AM and fluo-3/AM as fluorescent substrates of P-gp and MRP. The retention of dyes could be reached in both cell sublines by the application of inhibitors of P-gp (like verapamil) but not by probenecid - an inhibitor of anion transporters, including MRPs. Massive protein bands, at a M(r) range of 130-180 kDa that interact with c219 antibody against P-gp, were detected in the crude membrane fraction isolated from both R(V) and R(D) (but not from L1210) cells by Western blot. The cytosolic activity of glutathione S-transferase was found to be similar in R(V) and R(D) cells and did not differ significantly from the activity ascertained in parental L1210 cells. Neither the R(V) nor R(D) cell sublines differed considerably, as measured by cell ultrastructure. In conclusion, based on P-gp overexpression, both doxorubicin and vincristine induce a common multidrug resistance phenotype in L1210 cells.
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PMID:L1210 cells cultivated under the selection pressure of doxorubicin or vincristine express common mechanisms of multidrug resistance based on the overexpression of P-glycoprotein. 1696 37


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