Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.
 ...
PMID:Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems. 108 15

An antigen histochemically localized in the nuclei and cytoplasmic granules of normal and leukemic human myeloid cells has been identified as myeloperoxidase (MPO; EC 1.11.1.7). The localization and amount of the enzyme was determined by using a murine monoclonal antibody designated H-43-5 raised against nuclear proteins derived from human promyelocytic HL-60 leukemia cells. The highest amount of nuclear MPO (3.5 micrograms per 10(6) nuclei) was found in granulocytes; less than half of this amount was detected in nuclei from HL-60 cells. Still lower levels were found in nuclei from monocytes and a series of human monomyelocytic leukemia cells. MPO from HL-60 cells was purified by immunoaffinity chromatography and fractionated into three components (forms I, II, and III) by CM-cellulose chromatography. Chromatography of these MPO forms on DNA-Sepharose columns confirmed that all three forms of MPO were tightly bound to DNA with apparent relative affinities in the order of form III greater than form II greater than form I. The affinity of MPO form III for DNA was sufficient to enable the formation and elution of DNA-MPO complexes during size-exclusion chromatography at high ionic strength and neutral pH. This form of MPO was also able to shield DNA from strand scission induced by active oxygen species generated by xanthine oxidase acting aerobically on xanthine. These data suggest that intranuclear MPO may help to protect DNA against damage resulting from oxygen radicals produced during myeloid cell maturation and function.
 ...
PMID:Myeloperoxidase: a myeloid cell nuclear antigen with DNA-binding properties. 282 20

The value of intensified chemotherapy for improving event-free survival rates in childhood lymphoblastic leukemia (ALL) is now widely accepted among leukemia therapists. Still to be determined are (1) the optimal method of intensification, (2) the subset or subsets of patients for whom such treatment may be excessive, and (3) whether or not cure rates in ALL can be further improved by alternative approaches to intensification. St. Jude Total Therapy Study XI, based on predictions of the Goldie-Coldmand model of drug resistance, addresses some of these questions by use of rotational "non-cross-resistant" drug pairs throughout the course of therapy. A new method of risk classification has been developed to refine distinctions among prognostic subgroups, especially to identify patients with biologically unfavorable ALL. Unacceptable toxicity noted in the first 134 children enrolled in this study led to two protocol modifications. One hundred thirty-two patients have been treated subsequently without undue toxicity. The treatment is now being delivered safely. Our early experience with this regimen demonstrates some of the hazards of intensive multidrug combination treatment, but gains in leukemia control appear to justify this approach.
 ...
PMID:Intensified chemotherapy for childhood lymphoblastic leukemia: modifications and results of induction treatment in St. Jude Study XI. 321 44

The fate of the polycythaemic patient depends on the treatment employed which may determine the nature of the transformation commonly occurring late in the course of the disease. Treatment is, on the other hand, aimed at prevention of the most frequent complications, that is of thromboembolic processes. In the last 30 years the authors treated a total of 118 PV patients, of whom 60 have died. Initially 32P treatment was applied, which was modified later, because of acute leukaemia that had occurred in 9% of the treated cases, to a single 5 mC 32P+Myelobromol (DBM) treatment. Still later only DBM was administered in the form of stosstherapy (2500 mg per day over a period of 4 days). In the latter two groups, acute leukaemia occurred as few as two cases. The course of untreated polycythaemia vera is characterized by transformation into another myeloproliferative disease. This phenomenon occurs in 50% of the cases on drastic treatment and in patients treated with 32P. Of the patients who were alive when the report was finished 35% had been free of complications, while 5.2% were suffering from chronic granulocytic leukaemia (CGL), 34.5% from sclerotic osteo-myelofibrosis (OMF-SC) and 3.4% from chronic megakaryocytic granulocytiv leukaemia (CMGL). Of the 60 patients having died, 15% had suffered from other complications being predominantly of vascular nature. 11.8% of them died of AML, 10% of CGL, 26.7% of OMF-SC and 26.7% of CMGL. The terminal stage was characterized, in the majority of cases, by blastic crisis. Based on their own results and literary data authors recommend DBM treatment besides the indispensable phlebotomy.
 ...
PMID:Course and transformation of polycythaemia vera in relation to therapy. 341 64

To evaluate the potential teratogenicity and mutagenicity of modern cancer treatment, the authors enumerated from a cooperative clinical trial group 133 pregnancies in 66 women with malignant neoplasms (53% with Hodgkin's disease, 26% with other lymphomas and leukemia, and 21% with solid tumors). The gestations were divided into the following groups: Group 1, 43 pregnancies ending before therapy; Group 2, therapy given at conception or during 32 pregnancies; and Group 3, 58 pregnancies after therapy. Although the total frequencies of abnormalities were similar in Groups 1 and 2 (23% of 35 pregnancies not electively aborted and 28% of 25, respectively), there were slightly more elective abortions and birth defects related to radiation exposure at a susceptible time of gestation in Group 2. Still, there were eight normal infants among the ten fetuses who were liveborn and had first trimester exposure to chemotherapy alone; so, drug therapy early in pregnancy is not inevitably teratogenic. The apparent and surprising excess of abnormal outcomes in Group 3, 40% of 50 pregnancies, was due to low birth weight and premature terminations of pregnancy, rather than an excess of congenital anomalies. The type of unfavorable outcomes in Group 3 and their concentration in the first year posttherapy suggested they could represent defects in factors (e.g., uterine or hormonal) that normally maintain gestations, and not genetic damage to oocytes. Limitations of the data, collected by mail from physicians and their patients, included biases of self-reporting and low statistical power. Prospective study, probably through interinstitutional collaboration, seems necessary, if accurate estimates are to be made of the frequency of certain outcomes, such as spontaneous abortion and minor anomalies.
 ...
PMID:Pregnancy outcome in cancer patients. Experience in a large cooperative group. 360 30

The Balb/Mo mouse strain carries a single copy of the germ line integrated Moloney leukemia virus (M-MuL V) and shows a high leukemia frequency. According to the clinical manifestations lymphomas can be divided into two major categories. In one type the thymus appears to be the primary site for lymphoma development. The second type is dominated by the generalized enlargement of spleen and lymph nodes. Individual lymphomas differ in the cell surface expression of Thy 1.2, MCSA (designated operationally as the M-MuL V-determined cell surface antigen) and viral p30 antigens. In addition, spleen and thymus of the same leukemic animal often differ antigenically. The karyotype of cells from enlarged organs is diploid or shows trisomy of chromosome 15. Lymphomas developing in Balb/Mo mice are thus heterogeneous with regard to clinical manifestations, cell surface antigens and karyotype and, in this respect, do not differ from lymphomas arising after the inoculation of exogenous M-MuL V. Amplification of the M-MuL V genome in young Balb/Mo mice is not accompanied by the appearance of MCSA on thymus cells. Still, 32% of lymphomas are MCSA positive. The results suggest that MCSA is related to a virus activated in a minority of Balb/Mo mice during the late phase of leukemogenesis.
 ...
PMID:Antigenic and chromosomal changes in thymus and spleen of Balb/Mo mice during leukemogenesis. 712 Oct 53

Accompanying hematology laboratory automation, the frequency of morphological observation of blood cells tends to decrease. Although 5-part differentials are performed by automated systems, counting of abnormal cells such as immature cells or leukemia cells still must be performed manually using smears. In the automated hematology laboratories, technicians more frequently find abnormal cells than before. Therefore, poor microscopic observation of blood cells markedly affects the diagnosis. Continuous training of the technologist is mandatory. Also, preparation of smear samples is important, i.e, well prepared slides must be stained properly with an appropriate dye. Technicians must be familiar with staining technology together with the knowledge of the characteristics of several staining methods. On the other hand, the technician's ability to differentiate white blood cells depends on the instructor's knowledge. This makes quality control and the standardization of differentials difficult. Still the problems must be solved under the cooperation of the various societies concerned.
 ...
PMID:[Morphologic analysis of blood cells]. 747 55

Toxiusol, a natural product isolated from the Red Sea sponge Toxiclona toxius, has been shown to be a potent inhibitor of various viral reverse transcriptases (RT) [i.e., of human immunodeficiency virus (HIV-1), equine infectious anemia virus, and murine leukemia virus] and cellular DNA polymerases (i.e., of DNA polymerases alpha and beta and Escherichia coli DNA polymerase I). A thorough investigation of the mode of inhibition was conducted with HIV-1 RT-associated DNA polymerase activity. The inhibition is unaffected by the nature of template-primer used. The inhibitory active site of toxiusol is attributable to the polar moieties at the benzene ring. The presence of either sulfate groups in the natural lead compound or hydroxyl groups in the corresponding hydroquinone is critical, because both compounds are equally effective at low micromolar concentrations. Conversely, the presence of acetyl groups in the same position in the derivative toxiusol diacetate lowers significantly or abolishes the inhibitory activity. Toxiusol binds the HIV-1 RT irreversibly and in a noncompetitive way with high affinity (Ki = 1.2 microM), probably through polar groups. The replacement with acetyl moieties in the analog toxiusol diacetate hampers the binding of the inhibitor to the enzyme (Ki increases to about 26 microM). Still, the compound binds irreversibly, probably through its hydrophobic structure skeleton. Toxiusol diacetate loses its ability to inhibit the first step in the DNA polymerization process (that is, the formation of the DNA-enzyme complex as measured by a gel retardation assay), which contributes to its poor inhibitory capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mechanism of inhibition of HIV reverse transcriptase by toxiusol, a novel general inhibitor of retroviral and cellular DNA polymerases. 753 6

Exposure to radon and its decay products in mines is a well recognized risk of lung cancer in miners. A large number of epidemiologic studies from various countries are quite consistent in this respect even it the magnitude of the risk differs according to exposure levels. Indoor radon became a concern in the 1970s and about a dozen studies have been conducted since 1979, mainly of the case-control design. From first being of a simple pilot character, the designs have become increasingly sophisticated, especially with regard to exposure assessment. Crude exposure estimates based on type of house, building material and geological features have been supplemented or replaced by quite extensive measurements. Still, exposure assessment remains a difficult and uncertain issue in these studies, most of which indicate a lung cancer risk from indoor radon. Also a recent large scale study has confirmed a lung cancer risk from indoor radon. More recently there are also some studies, mainly of the correlation type, suggesting other cancers also to be related to indoor radon, especially leukemia, kidney cancer, and malignant melanoma, and some other cancers as well. The data are less consistent and much more uncertain than for indoor radon and lung cancer, however; and there is no clear support from studies of miners in this respect.
 ...
PMID:Cancer risks from exposure to radon in homes. 761 45

Trends in age-specific and age-standardized mortality from 10 major cancer sites and total cancer mortality in the USSR were analyzed for the period 1965-1990, on the basis of the World Health Organization mortality database. Gastric cancer mortality declined substantially. Still, these rates were among the highest registered in the world, and in 1990 stomach cancer accounted for over 85,000 deaths, being the second cause of cancer death (and the first one until 1980); further, there was some indication of a levelling of the declines in gastric-cancer rates for both sexes over most recent calendar years. Likewise, uterine-cancer mortality declined between 1965 and 1985, but there was no further decline over the last 5 years. Upward trends were registered for cancers of the intestine, of the breast and of the prostate. Mortality from these neoplasms, however, was still comparatively low by worldwide standards. Leukaemia rates were stable in both sexes. Substantial rises were observed for cancers of the oral cavity and pharynx, larynx and, chiefly, lung. Even more unfavourable was lung-cancer mortality in young and middle-aged males, since the truncated rate of 121/100,000 in 1990 was higher than the values reached by countries like England and Wales or Finland even at the top of their epidemic in the 1960s, and trends in the USSR were still upwards. Thus, total cancer mortality was 176/100,000 males in 1965, declined to 170 in 1970, but increased thereafter, particularly over the last decade, to reach 203/100,000, i.e., one of the highest rates on a worldwide scale. Among females, the overall cancer mortality rate declined between 1965 and 1975, but rose thereafter to a value intermediate on a worldwide scale. These recent unfavourable trends of cancer mortality in the USSR indicate that, in the absence of adequate intervention, particularly on the tobacco-related cancer epidemic, overall cancer mortality will continue to rise in the foreseeable future.
 ...
PMID:Trends in cancer mortality in the USSR, 1965-1990. 826 75


1 2 3 4 5 Next >>