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10,004,200 | A monoclonal antibody (CALed) against a human pulmonary squamous cell carcinoma line was cytotoxic to the line but did not react to an autologous B-lymphoblastoid line. Although the antibody was thought to be cancer specific, principally on the basis of this evidence, the antibody actually had the A1 Lewis d (Led) specificity. It reacted with approximately 2% of the random donor T-lymphocytes and with all six lymphocytes from donors who were A1 Led type without reacting to lymphocytes of any other type. The monoclonal antibody reactivity was also absorbed out by A1 Led red blood cells but not by red cells of other types. We conclude that the A1 Led antigen had been synthesized by the pulmonary carcinoma lines but not by the autologous lymphoblastoid line, resulting in disparity for this antigen. Since the combination A1 Led only occurs in 2% of the population, it is difficult to distinguish this type of antibody from tumor-specific antibodies. | [
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10,004,201 | Stimulation of DNA synthesis and cell proliferation in the liver of rats fed a choline-devoid diet and their suppression by phenobarbital. | [
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10,004,202 | Feeding of choline-devoid (CD) diet and dietary administration of phenobarbital (PHB) are efficient promoters of liver carcinogenesis in the rat. Furthermore, inclusion of PHB in a CD diet results in a synergistic effect, inasmuch as the promoting action of their combination is greater than the sum of those exerted by either agent alone. To investigate the mechanism(s) of action of the two promoters, liver DNA synthesis and liver cell proliferation were studied in rats fed a CD diet, a choline-supplemented diet, or the same diets to which 0.06% PHB was added. DNA synthesis was determined by [3H]thymidine incorporation into DNA and autoradiography, and cell proliferation was determined by mitosis counts. Feeding the CD diet caused an increase of both DBA synthesis and cell proliferation over those present in rats fed the choline-supplemented diet. Inclusion of PHB in the CD diet, on the other hand, inhibited DNA synthesis and cell proliferation. These results indicate that stimulation of cell proliferation per se may not be a sufficient condition for an agent to act as a promoter of liver carcinogenesis. | [
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10,004,203 | Association of impaired immune responsiveness of lymphocytes from animals bearing large tumors with a membrane-bound suppressive substance. | [
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10,004,204 | The immunoreactivity of lymphocytes from mice bearing large tumors was investigated. As compared to normal lymphocytes, lymphocytes from tumor bearers manifested a lessened proliferative response to T-cell mitogens and were less capable of destroying syngeneic tumor target cells. However, the impaired reactivity of these lymphocytes was improved significantly after washing repeatedly in tissue culture medium in vitro. The increase in cytolytic activity was tumor specific. A membrane-associated suppressive substance was detected in the washing medium which inhibited the cytotoxicity of washed lymphocytes. The effect of suppressive substance was tumor specific and sensitive to treatment with protein A and anti-immunoglobulin antibody, indicating that the suppressive substance contained immunoglobulin. The present findings suggest that a membrane-associated suppressive substance(s) may be in part responsible for the diminished immune responsiveness of lymphocytes from animals bearing large tumors. | [
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10,004,205 | Molecular basis for increased synthesis of albumin in rat liver after thioacetamide administration. | [
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10,004,206 | Administration of thioacetamide to rats for 4 days has been shown previously to increase the activity of liver messenger RNA (mRNA) and to disproportionately increase the activity of albumin mRNA in the wheat germ translation system. We have explored the possibility that administration of thioacetamide quantitatively alters the transcription of rat liver unique DNA. Nucleic acid hybridization between the radioactive rat liver unique DNA and RNA from untreated as well as 4-day thioacetamide-treated rat liver indicates that the normal extent of transcription is not altered by the drug treatment. We also investigated the possibility that thioacetamide treatment increases the level of mRNA in general or of albumin mRNA in particular. Albumin mRNA, which is th most abundantly represented population in rat liver cytoplasmic mRNA, was further enriched by sucrose gradient fractionation of the liver mRNA. Synthesis of complementary DNA (cDNA) and then use of the strategy of limited hybridization yielded the cDNA corresponding to albumin mRNA. Hybridization of the fractionated cDNA with mRNA from untreated livers as well as from livers with increasing days of treatment shows no change in the level of albumin mRNA. The results indicate that drug treatment induces the augmented synthesis of albumin by disproportionately increasing the translational activity of albumin mRNA. Quantitation of gene dosage by comparison of hybridization kinetics of fractionated cDNA and unique [3H]DNA with total rat cellular DNA indicates that there are not more than two copies of the albumin gene present in the rat genome. | [
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10,004,207 | Effect of the suspected tumor promoters saccharin, cyclamate, and phenol on nerve growth factor binding and response in cultured embryonic chick ganglia. | [
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10,004,208 | The suspected bladder tumor promoters saccharin and cyclamate reversibly inhibited nerve growth factor-induced neurite outgrowth in embryonic chick sensory ganglia, and active concentrations of these artificial sweeteners inhibited binding of 125I-labeled mouse submaxillary gland nerve growth factor as well. The skin tumor promoter phenol also reversibly inhibited neurite outgrowth, while comparable concentrations of the nonpromoting but structurally related compounds benzene and fluorobenzene did not. However, in contrast to findings with saccharin and cyclamate, phenol had little, if any, effect on binding of radioactive nerve growth factor. | [
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10,004,209 | Paradoxical effect of radiation on tumor incidence in the rat: implications for radiation therapy. | [
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10,004,210 | The high incidence of leukemia in the Fischer rat is reduced by radiation to an incidence below that seen spontaneously. Fractionating the radiation decreased this effect. In contrast, mammary tumors increased with dose until reaching a plateau at the highest doses. Fractionation had little effect. These results are consistent with a hypothesis suggesting that tumor incidence due to radiation is the result of competing processes of tumor induction and cell killing. | [
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10,004,211 | Activity of a novel anthracenyl bishydrazone, 9,10-anthracenedicarboxyaldehyde Bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride, against experimental tumors in mice. | [
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10,004,212 | 9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride (CL 216942; bisantrene hydrochloride; NSC 337766), a member of a new chemical class of compounds with antineoplastic properties, has been evaluated for antitumor activity in experimental murine tumor systems. The compound produced significant increases in life span (LS) and long-term survivors among mice bearing transplantable leukemias and solid tumors. Optimal treatment regimens resulted in an ILS of greater than 173 and 151% in mice with P388 and L1210 leukemia, respectively, an ILS of greater than 85% in mice with Lieberman plasma cell tumor, and an ILS of greater than 200, 150, and 63%, respectively, in mice with B16 melanoma, colon tumor 26, and Ridgway osteogenic sarcoma. An adriamycin-resistant subline of P388 leukemia showed complete cross-resistance to CL of 216942. The compound was active when administered by the i.p., i.v., and s.c. routes, but p.o. activity was not observed. Significant schedule dependency was not observed when the drug was administered once daily for 9 days, once every 4 days, or as a single dose, but single doses typically produced the best effects. CL 216942 was a potent inhibitor of DNA and RNA synthesis in L5178Y lymphoma cells cultured in vitro, and preliminary studies indicated the drug was a DNA-intercalating agent. The drug was cytotoxic for rapidly proliferating and nonproliferating (G0) human colon carcinoma WiDR cells in vitro.U | [
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10,004,213 | Enhanced transformation of mouse 10T1/2 cells by 12-O-tetradecanoylphorbol-13-acetate following exposure to X-rays or to fission-spectrum neutrons. | [
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10,004,214 | Addition of the tumor promoter of 12-O-tetradecanoylphorbol-13-acetate (TPA) to C3H/10T1/2 cells after exposure to either X-rays or to fission-spectrum neutrons increases significantly the frequency of transformation without any effect on cell survival. However, treatment of unirradiated cells with 0.1 micrograms of TPA per ml alone results in a small increase in transformation frequency above background (i.e., from 1.1 x 10(-5) to 1.0 x 10(-4). Thus, besides being a promoter, TPA is also a weak initiator. Enhancement of radiation-induced transformation by TPA was relatively greater after low compared to high doses of either radiation. In addition, TPA causes the relative biological effectiveness of neutrons compared to X-rays to increase with increasing dose or with increasing frequency of transformation rather than to decrease, when TPA is not used. For X-ray doses from zero to approximately 120 rads, TPA raises transformation to frequencies approximately equal to those due to neutrons alone. Analysis of TPA enhancement in the context of the combined effect of two inducing agents, i.e., TPA plus a radiation, indicates that with either radiation TPA acts synergistically. Lastly, TPA was found to alter the dependence of transformation frequency on the density of viable cells. As opposed to a constant frequency of transformants per surviving (or viable) cell, which we observed after a fixed dose of X-rays or neutrons for a range of cell inocula, the addition of TPA increased the frequency of transformation for cell inocula (i.e., from approximately 20 to 6000 viable cells per 90-mm Petri dish). However, the frequency of transformation decreases with increasing size of the inoculum, a result that we interpret to indicate the combined effect of an interference with cell-to-cell communication by TPA plus the fading of initiation events due to the radiation. | [
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10,004,215 | Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators. | [
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10,004,216 | Liposomes containing encapsulated lymphokines or muramyl dipeptide (MDP), when injected i.v. into C57BL/6 mice, produced significant destruction of established lung and lymph node metastases from a s.c. highly metastatic B16-BL6 melanoma. We present evidence that eradication of the metastases is mediated by the activation of host macrophages to the tumoricidal state. Results from three separate types of experiments support this conclusion. (a) When macrophage-activating agents such as lymphokines of MDP were delivered in liposomes that were not efficiently retained in the lung, little or no activation of lung macrophages was observed, and growth of metastases was unaltered. (b) Eradication of metastases was not observed when tumor-bearing animals were treated with agents that impaired macrophage function (e.g., silica, carrageenan, hyperchlorinated drinking water) prior to systemic therapy with liposome-encapsulated lymphokines or liposome-encapsulated MDP. (c) Macrophages activated in vitro by liposome-encapsulated MDP and then injected i.v. into mice bearing experimental lung metastases also significantly inhibited lung metastases. These results suggest that the augmented host response against pulmonary and lymph node metastases generated by the systemic administration of liposome-encapsulated lymphokines or MDP is mediated via activated cytotoxic macrophages. | [
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10,004,217 | Fluoresceinated estrone binding by human and mouse breast cancer cells. | [
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10,004,218 | Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma. | [
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10,004,219 | Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver and 100 for "back-ground" tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 microgram CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the 10B(n, alpha)7Li reaction. | [
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10,004,220 | Induction of alkaline phosphatase activity in cultured human intracranial tumor cells. | [
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10,004,221 | Alkaline phosphatase activity in several cultured primary human intracranial tumor cells varied over a relatively wide range, and there was no correlation between specific activity and the type of tumor from which the cultures were derived. The enzyme was thermolabile, and its activity was strongly inhibited by l-bromotetramisole, levamisole, and L-homoarginine but not by L-phenylalanine and L-phenylalanyglycylglycine. These are the characteristics of the liver-bone-kidney form of alkaline phosphatase. Prednisolone induced increased levels of enzyme activity in most cultures, and sodium butyrate acted as an inducer in cultures of pituitary adenoma and hemangioblastoma cells. The increase was most pronounced when response cells were exposed to both stimuli simultaneously. The induced alkaline phosphatase had the same properties as the enzyme of cells grown in the absence of inducers. Increased alkaline phosphatase activity was not induced by osmolality changes of the culture medium; this feature appears to be characteristic of cells producing the liver-bone-kidney enzyme form. | [
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10,004,222 | Expression of the tumor aldehyde dehydrogenase phenotype during 2-acetylaminofluorene-induced rat hepatocarcinogenesis. | [
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10,004,223 | In aromatic amine-induced rat hepatomas, the aldehyde dehydrogenase (AIDH) phenotype is qualitatively and quantitatively different from that of normal liver. To identify the mechanism(s) underlying the expression of the tumor-specific AIDHs, we have followed the time course of appearance of the new phenotype during hepatoma formation in Sprague-Dawley rats following brief dietary exposures to 2-acetylaminofluorene (0.02%; 32 days). Tumor promotion by phenobarbital (0.05% in the diet) was also used to compare the effects of a variety of tumor induction protocols on the AIDH phenotype. No change in the AIDH phenotype is detectable by total activity assay, gel electrophoresis, isoelectric focusing, or immunochemical methods during or following exposure to carcinogen or promoter until tumors are grossly observed in liver. Concomitant with tumor appearance, the tumor-specific AIDH phenotype appears. The phenotypic change is limited to the tumor; morphologically and histologically normal liver directly adjacent to the tumor and normal lobes of a tumor-bearing liver do not possess the tumor AIDH phenotype. No correlation exists between tumor size and the degree of deviation of the AIDH phenotype from normal. Nor is there any correlation between the degree of AIDH phenotype deviation and the histology of the various tumors observed. We conclude that the tumor-specific AIDH phenotype is not associated with altered liver metabolism due directly to carcinogen or promoter exposure. Rather, the mechanism of this phenotypic change requires that transformation-associated, stable genetic changes occur in the cells affected by carcinogen that are later expressed as the altered AIDH phenotype. | [
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10,004,224 | Comparative physiological disposition of N-(phosphonacetyl)-L-aspartate in several animal species after intravenous and oral administration. | [
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10,004,225 | The physiological disposition of N-(phosphonacetyl)-L-aspartate (NSC 224131; PALA), a potent inhibitor of aspartate transcarbamylase, has been studied in mouse, rat, dog, and monkey after administration of [14C]PALA at 120 mg/sq m i.v. or p.o. Concentrations of PALA equivalents in plasma, urine, and feces were determined radiochemically, and urine was analyzed chromatographically for PALA. The disposition of PALA equivalents in mouse tissues was determined radioautographically. After i.v. administration, PALA was rapidly (half-time, approximately 1 hr) and extensively (up to 80% of the dose) excreted in the urine of all species. Less than 5% was excreted in the feces. Only PALA was found in the urine of all four species, indicating that the metabolism of PALA, if it occurs at all, is insignificant. PALA equivalents were poorly taken up by mouse tumors and tissues, except kidney, bone, and to a lesser extent, skin and lung, and were rapidly and extensively cleared from all except bone. No differences were apparent in the uptake of PALA equivalents by Lewis lung carcinoma (sensitive to PALA treatment) and L1210 lymphocytic leukemia (insensitive). The pharmacokinetics of PALA in the plasma of rat, dog, and monkey, as well as mouse, were inconsistent with deposition of PALA in tissues and more consistent with the probable distribution of PALA into extracellular water. PALA equivalents were eliminate from all species at a rate (half-time, 1 to 1.5 hr) reflecting the rate of urinary excretion of the drug and at a secondary slower rate probably reflecting the rate of release of bound PALA from sites such as aspartate transcarbamylase. PALA was poorly absorbed into the systemic circulation when administered p.o., in that mouse, rat, and monkey excreted less than 5% of the dose in the urine after p.o. administration. These data on the physiological disposition of PALA explain why high doses of the drug have to be administered to achieve therapeutic and toxic effects, despite the inhibitory potency of the drug on aspartate transcarbamylase. They indicate that PALA will be ineffective administered p.o. and might be contraindicated in patients with impaired renal function and that the kinetics of aspartate transcarbamylase-bound drug is probably more important in determining dose scheduling than the kinetics of free PALA. | [
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10,004,226 | Purification and partial characterization of a 17 beta-estradiol-binding macromolecule in the human pancreas. | [
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10,004,227 | Studies have been performed in order to investigate the presence of estrogen-binding proteins in the human pancreas that may provide the biochemical basis for tissue-specific treatment of pancreatic carcinoma with estrogen-based cytotoxic drugs. Using in vitro techniques, an estrogen-binding macromolecule has been purified from pancreatic cytosol. With estradiol a ligand, Kd was calculated to be 1.7 X 10(-7) M, and this protein was found to constitute about 4% of the total protein content in the cytosol. No metabolism of estradiol was detected under the in vitro conditions used. Competition experiments indicated that, besides estradiol, the protein also had some affinity for estrone and estriol but not for testosterone, progesterone, or dexamethasone. The protein was purified to homogeneity using chromatography on concanavalin A and hydroxylapatite followed by preparative polyacrylamide gel electrophoresis. The purified protein, still able to bind, [3H]-estradiol, gave one single protein-staining band when analyzed using different electrophoretic systems. The steroid-protein and did not bind to phosphocellulose or DNA-cellulose and did not show any similarities to steroid receptor proteins. The complex has a Strokes' radius of 52 A and a sedimentation coefficient of 3S. The biological significance of the macromolecule is known, but the protein is probably synthesized in the pancreas since no similar protein could be detected in serum. Studies are now being carried out to investigate whether this novel protein in the human pancreas may interact with complexes between cytotoxic agents and estrogens and provide the basis for tissue-specific treatment of pancreatic carcinoma. | [
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10,004,228 | Protection of mice against lethal doses of 1 beta-D-arabinofuranosylcytosine by pluripotent stem cell inhibitors. | [
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10,004,229 | The aim of this work was to study whether an inhibitor of pluripotent stem cell (CFU-S) recruitment, which we have shown previously to be able to increase the number of CFU-S after a fractionated treatment with 1-beta-D-arabinofuranosylcytosine, could increase the survival of mice given injections of lethal doses of the same drug. Two protocols of 1-beta-D-arabinofuranosylcytosine treatment were used in two different mouse strains, which both killed the mice within a week. An inhibitor of CFU-S was prepared by dialysis from fetal calf marrow, and a first step of purification was made by chromatography on Sephadex G-10. When given injections 2 hr before the drug, the number of surviving mice was increased significantly with the dialysate; fractions separated by chromatography appeared to be more effective to increase the animal survival. These preliminary results indicate that a factor of low molecular weight (below M.W. 3500) extracted from fetal calf marrow is able to protect animals during 1-beta-D-arabinofuranosylcytosine treatment. The inhibitor seems to be specific for CFU-S, without any inhibiting effect on tumor cell kinetics in vitro. If the absence of species specificity found for higher to lower species is confirmed for the lower to the higher species, then this inhibitor could be an effective tool during cancer chemotherapy. | [
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10,004,230 | Effect of estradiol on the ultrastructure of the MCF7 human breast cancer cells in culture. | [
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10,004,231 | We have analyzed the effect of estradiol and of two classes of antiestrogens on the morphology of the MCF7 human breast cancer cell line by scanning and transmission electron microscopy. Estradiol progressively increased the number and the length of microvilli at the cell surface. The density of the microvilli network increased between 2 and 11 days of estrogen treatment, while the cells became more granular and less tightly attached to the surface of the dish. Estradiol also progressively transformed cells into secretory cells containing, at Day 2, large, clear mitochondria and, at Day 4, rough endoplasmic reticulum and Golgi complex. At Day 6, secretory granules (diameter, 0.2 microM), which mainly contained glycoproteins, were first developed in the cytoplasm. By Day 8, they were concentrated at the cell membrane and being liberated into the medium. Larger granules (diameter, 0.8 microM), which probably contained lipids, were obtained later (Day 11). Cell cultures in 10% fetal calf serum not treated by charcoal contained secretory granules. The modifications were induced by physiological concentrations of estradiol but not 5 alpha-dihydrotestosterone. Progesterone (10 nM for 8 days) completely inhibited the effect of estradiol on the microvilli and secretory activity. Tamoxifen or hydroxy-tamoxifen did not induce secretory activity but did alter the cell morphology compared to control cells. The effects of estradiol were observed in other estrogen receptor-positive breast cancer cell lines (ZR 75-1, T 47 D) but not in an estrogen receptor-negative cell line (BT 20). This morphological evidence that estrogens modify the cell surface of breast cancer cells in culture and transform them into "secretory cells" complements evidence that a molecular weight of approximately 50,000 into the culture medium (Cell, 24: 352-362, 1980). (The molecular weight was found first to be 46,000. It seems to be closer to 52,000 in a 10% polyacrylamide gel and by using the NEN-labeled proteins as molecular weight markers. | [
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10,004,232 | Pediatric cancer and nutrition workshop. | [
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10,004,233 | Pediatric cancer and nutrition workshop: introductory comments. | [
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10,004,234 | Nutritional assessment of the child with cancer. | [
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10,004,235 | Children with cancer are in need of nutritional support to combat the catabolic effects of malignant tumors and debilitation from surgical or other treatment and complicating infections and to maintain their immune system and other host defenses to combat cancer and infection. Also, growth must be supported in the child. Nutritional assessment should be an integral part of the care of the hospitalized and the ambulatory child. The main components of nutritional assessment are described: medical history; psychocultural history; dietary assessment; clinical examination for signs of deficiency; anthropometry; and biochemical and hematological assessment. Parameters of cell-mediated immunity, often depressed by malnutrition, are also part of the assessment. Appropriate reference data for children are included. Assessment is the first step in nutritional support. | [
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10,004,236 | Pathophysiology of cancer cachexia: current understanding and areas for future research. | [
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10,004,237 | Weight loss and failure to gain weight normally in cancer patients are attributable to negative energy balance and altered metabolism. Energy balance is negative because of decreased intake, increased expenditure, or both. Changes in carbohydrate metabolism include glucose uptake and lactate production by tumor, relative hypoinsulinism, and relative insulin resistance. Alterations in protein metabolism include preferential uptake of amino acids by the tumor, decreased synthesis of some host tissue proteins such as muscle tissue, and increased synthesis of other host proteins. Lipid metabolism is seemingly less affected. These metabolic changes result in muscle wasting in adult cancer patients and growth failure in pediatric cancer patients. Host tissues are catabolized to meet the nutritional demands of tumor, and nutritional death may ensue. | [
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10,004,238 | Tumoricidal potential of nutritional manipulations. | [
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10,004,239 | Perturbations of specific nutrient availability is the basis of a large number of chemotherapeutic modalities used in cancer treatment. The creation of transient nutrient deprivation states by deficient diets (deficiency), nutrient destruction or displacement (depletion), the presence of antimetabolites or analogs (deficiency state), or combinations of the above has shown significant antitumor effect in several animal and human cancers. Pair-fed isocalonic diets deficient in micronutrients such as carbohydrates (with or without gluconeogenesis inhibition) or micronutrients such as zinc or pyridoxine have demonstrated antitumor potential. Amino acid depletion by enzymes such as L-asparaginase or L-glutaminase has become a popular modality for treatment of human leukemias. Purine and pyrimidine analogs or folate antimetabolites have been used successfully for several decades in the treatment of human tumors. Excess pyridoxine in tissue culture has demonstrated antineoplastic potential. Dietetic supplementation with naturally occurring sugars, sugar derivatives, or analogs has also demonstrated tumorotropic effects. | [
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10,004,240 | Phase II trial of combination therapy with continuous-infusion PALA and bolus-injection 5-FU. | [
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10,004,241 | Fifty-seven patients were treated with continuous infusion of PALA at a dose of 850 mg/m2/day x 5 and iv bolus injection of 5-FU at a dose of 300 mg/m2/day x 5, which was given at the end of each 24-hour PALA infusion; the treatment interval was 28 days. The overall response rate among 43 evaluable patients was 14%. Two of 21 patients (10%) with colorectal carcinoma, two of eight patients with pancreatic carcinoma, and two of four patients with breast carcinoma achieved partial responses lasting 2-12 months. One of the responding patients with colon cancer and two with breast cancer had failed to respond to prior therapy with 5-FU; one of the responding patients with breast cancer had previously received an inadequate trial of a similar regimen. Toxic effects were mild to moderate and were confined to oral mucositis in most patients. It is concluded that this regimen offers little enhancement of the antitumor activity of 5-FU in patients with colorectal cancer previously treated with 5-FU. Investigation of other infusion techniques for the PALA and 5-FU combination is recommended, with particular attention to the treatment of colorectal, pancreatic, and breast carcinomas. | [
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10,004,242 | Vindesine in the treatment of squamous cell carcinoma, adenocarcinoma, and large cell carcinoma of the lung. | [
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10,004,243 | The antineoplastic activity of vindesine was evaluated in a phase II trial in patients with squamous cell carcinoma, adenocarcinoma, and large cell carcinoma of the lung. Sixty-three patients participated in the trial: 22 with squamous cell carcinoma, 25 with adenocarcinoma, and 16 with large cell carcinoma. Most of the patients had not received prior treatment; six had received single-agent chemotherapy. The dose of vindesine was 4 mg/m2 every 2 weeks, reduced or increased according to hematologic and neurologic side effects. Fifty-four patients were evaluable. Objective response was observed in two of 19 patients with squamous cell carcinoma (11%), in six of 22 patients with adenocarcinoma (27%), and in one of 13 patients with large cell carcinoma (8%). In patients with adenocarcinoma the median duration of response was 196 days (range, 71-450+). Twenty-five percent of the evaluable patients received greater than or equal to 100% of the scheduled dose. In 39% of the patients, dose reductions were necessary because of leukopenia, and in 63%, dose modifications were necessary because of neurotoxic effects. It is concluded that vindesine as a single-agent chemotherapy is active against adenocarcinoma of the lung. Activity in squamous cell carcinoma and large cell carcinoma appears to be less, but not totally absent. | [
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10,004,244 | Isolation and properties of Chinese hamster lung cells resistant to ellipticine derivatives. | [
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10,004,245 | Chinese hamster lung cells resistant to 9-OH-ellipticine (9-OH-E) were selected in vitro by adding stepwise increasing drug concentrations to the cell growth medium. This selection procedure resulted in the isolation of two sublines, about tenfold and 12-fold resistant to 9-OH-E. This level of resistance did not increase even after about 30 months of drug exposure. Cytogenetic studies revealed that the resistant cells carry several discrete karyotype modifications, the most striking being the absence of one No. 5 chromosome and the presence of a marker chromosome characterized by peculiar G-banding. Development of 9-OH-E resistance was also associated with some changes in cell properties such as modifications of morphology and growth parameters, lower oncogenic potential, and cross-resistance to a variety of antitumor agents. Although these results suggest that the resistance is associated with a modification of cell membrane properties, drug uptake studies did not show any significant difference between the parental sensitive cells and the resistant sublines. | [
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10,004,246 | Biochemical and pharmacologic properties of a new folate analog, 10-deaza-aminopterin, in mice. | [
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10,004,247 | Phase II study of a high-dose regimen of cyclophosphamide and prednisolone in advanced non-Hodgkin's lymphoma of favorable histologic type. | [
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10,004,248 | Fifty-seven courses of cyclophosphamide (2.5-5.0 g/m2) and prednisolone (1.0 g/m2 x 5) were given to 22 patients with advanced stage IV non-Hodgkin's lymphoma of favorable histology. Six patients (27%) had a complete response (CR) (median duration, 10.1 months), and six (27%) had a partial response (median duration, 3.0 months). All patients in whom CR was achieved had a previous disease pattern of remission and relapse, and no patient refractory to previous therapy had a CR. This association of CR to disease pattern was statistically significant (P less than 0.0001). There was no difference in the survival of complete and partial responders. There was a trend to a higher response rate and statistically significant survival advantage (P less than 0.05) for patients with the nodular histologic types. The transient nature of response and the toxicity of the regimen, with four therapy-related deaths, render it unsuitable as routine therapy. | [
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10,004,249 | Phase II study of anguidine in gastrointestinal malignancies: a Southwest Oncology Group study. | [
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10,004,250 | The Southwest Oncology Group conducted a phase II study of anguidine in 134 patients with gastrointestinal malignancies. Anguidine was administered as a 4-hour infusion at doses of 3.0 and 4.5 mg/m2 daily x 5. Response rates for patients with colon carcinoma were 22% (four of 18 patients without previous chemotherapy) and 6% (four of 63 patients with previous chemotherapy). There were no responses in patients with pancreatic cancer (four patients) or gastric cancer (six). Toxic effects included thrombocytopenia (19.8%), leukopenia (18.8%), nausea and vomiting (49%), hypotension (37%), and confusion (12%). Antitumor activity of anguidine in patients with colon cancer may be similar to that of 5-FU, but nonhematologic toxicity is substantial. | [
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10,004,251 | Chemoimmunotherapy for autochthonous acute rat leukemias. | [
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10,004,252 | Eighty autochthonous acute rat leukemias that had been induced by ethylnitrosourea were used to compare the effect of single-drug therapy with vincristine, doxorubicin, or cytarabine with the effect of combination therapy using these three drugs with or without BCG-Pasteur F. The combination chemotherapy was clearly superior to the single-drug therapy. The best results (survival time; duration of remission) were achieved by vincristine, doxorubicin, and cytarabine plus BCG, although compared to the combinations without BCG, these results were not significant. | [
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10,004,253 | Comparative cardiac and renal toxicity of daunorubicin in the rat and rabbit. | [
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10,004,254 | A direct comparison of the cardiac and extracardiac effects of repeated daunorubicin administration in the rat and rabbit demonstrated a basic similarity in the cardiac myocyte response. The rat, however, appears to develop a more severe drug-related nephropathy, resulting in widespread soft tissue mineralization that includes vessels and the myocardium. These findings suggest that the severity and development of acute and chronic anthracycline-induced cardiac lesions may, in the rat, be related or dependent, in part, on concomitant nephrotoxicity. | [
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0.1418779641... |
10,004,255 | Phase II evaluation of VM-26 in patients with metastatic transitional cell carcinoma of the urinary tract: an Eastern Cooperative Oncology Group study. | [
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10,004,256 | Synthesis of L-idaro-1,4-lactone, an inhibitor of alpha-L-idosiduronase. | [
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10,004,257 | L-idaro-1,4-lactone was synthesized by two different, published methods: (1) epimerization of monopotassium D-glucarate by refluxing in aqueous barium hydroxide, and (2) oxidation of L-iditol by heating in dilute nitric acid. The lactone, formed by heat dehydration from aqueous solution at low pH, was purified by paper chromatography, and quantitated by gas-liquid chromatography using inositol as the internal standard. The monolactone inhibited human, seminal-fluid alpha-L-idosiduronase activity, with either phenyl or 4-methylumbelliferyl alpha-L-idosiduronic acid as the substrate, to the same degree as D-glucaro-1,4-lactone inhibits alpha-D-glucosiduronase. | [
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10,004,258 | Methyl derivatives of 2-acetamido-2-deoxy-3-O-(beta-D-glucopyranosyluronic acid)-D-glucose (hyalobiouronic acid) from methylated hyaluronic acid. | [
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10,004,259 | Methanolysis of methylated hyaluronic acid, followed by acetylation, gave, in 70% yield, crystalline methyl 2-acetamido-2-deoxy-4,6-di-O-methyl-3-O-(methyl 4-O-acetyl-2,3-di-O-methyl-beta-D-glucopyranosyluronate) -alpha-D-glucopyranoside. Removal of the O-acetyl and methyl ester groups gave compounds that are useful in the investigation, by 1H-n.m.r. spectroscopy, of interaction within chains of hyaluronic acid in solution. | [
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10,004,260 | [Health policy and tasks for medical science after the 16th Congress of the Czechoslovak Communist Party]. | [
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0.02... |
10,004,261 | [Renal osteopathy in patients receiving regular haemodialysis (author's transl)]. | [
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0.0878719761967659,
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-0.055... |
10,004,262 | [Physical perfection, physical fitness and exercise]. | [
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0.05462558940052986,
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-0.08813... |
10,004,263 | [Electrocapacitance vulvoplethysmography (author's transl)]. | [
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0.0925... |
10,004,264 | [Intensive physical training and its effect on the urine excretion of catecholamines and 17-OH corticoids during aerobic exercise on an ergometer (author's transl)]. | [
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0.... |
10,004,265 | [The effect of environment and physical exercise on red blood count in elite female swimmers (author's transl)]. | [
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0.0... |
10,004,266 | [Pedagogical training of medical school teachers in the USSR (author's transl)]. | [
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0.0517... |
10,004,267 | [Medical students' attitudes to examinations (author's transl)]. | [
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0.00707220... |
10,004,268 | Penetration of the peritrophic membrane of the tick by Babesia microti. | [
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10,004,269 | A peritrophic membrane (PM) has been demonstrated in the gut of feeding larvae, nymphs, and adults of the tick Ixodes dammini. This is the first report of a PM in ticks. This temporary structure divides the lumen of the gut into two compartments, an endoperitrophic space, the lumen proper, and an ectoperitrophic space located between the PM and the epithelial cells of the gut wall. The PM is a mechanical barrier and even such small particles as ribosomes derived from ingested reticulocytes are retained in the lumen proper; they are never found in the ectoperitrophic compartment. In Ixodes dammini fed on hamsters infected with Babesia microti some of the parasites are found in the ectoperitrophic space. This passage is accomplished by a highly specialized organelle, the arrowhead, which develops in some Babesia during their metamorphosis in the gut of the vector. The arrowhead, while passing through the PM, changes its fine structure and loses its internal organization as if releasing some of its contents. Its disintegration continues and it disappears shortly after the Babesia have entered the epithelial cells. Only Babesia equipped with the arrowhead structure are able to cross the PM. This is the first documented case of a parasite traversing a solidified PM. | [
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0.04... |
10,004,270 | Glucagon and glicentin immunoreactive cells in human colon. | [
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10,004,271 | An immunohistochemical study of glucagon and glicentin immunoreactive endocrine cells in the human colon epithelium was performed. Serial sections and qualitative analysis show a cell population containing both immunoreactivities. However, there is another cell population exhibiting only an immunoreactivity with glicentin. The exact distribution of these immunoreactive endocrine cells within the colon crypt segments is also analysed. The significance of these findings concerning the synthesis of glucagon and glicentin and their function is discussed. | [
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10,004,272 | Marked reduction in intramembranous particle clusters in the terminal portion of inner medullary collecting ducts of antidiuretic rats. | [
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10,004,273 | Antidiuretic hormone (ADH) induces an aggregation of intramembranous particles (IMP) into discrete clusters in the luminal plasma membrane of rat renal papillary collecting duct cells (Harmanci et al. 1978). The correlation between an elevated dose of ADH, increased urine osmolality, and greater IMP cluster frequency has led to speculation that the water permeability of the luminal plasma membrane is reflected by the IMP cluster density (Harmanci et al. 1980). The present study indirectly evaluated this water permeability by quantitating collecting duct IMP cluster frequency from freeze-fracture replicas in two regions of the renal papilla, at its base and at its tip, in antidiuretic and in water diuretic rats. During antidiuresis there was a high frequency of IMP clusters (189/100 micron2 of luminal plasma membrane) in cells from the papilla base but not at the papilla tip (9.0/100 micron2). During water diuresis there were few IMP clusters in either cells from the papilla base (5.9/100 micron2) or at the papilla tip (1.4/100 micron2). Most significantly these results suggest that the water permeability of the terminal portion of the inner medullary collecting duct of antidiuretic rats is significantly lower than that of the collecting duct epithelium higher in the papilla. | [
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10,004,274 | Fine structural examination of the single heart tube in the fifteen day ferret embryo. | [
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10,004,275 | The different segments of the embryonic heart tube of the ferret were examined with light and transmission electron microscopy. The cells of bulbus cordis, bulboventricular junction, primitive ventricle, atrioventricular junction, and primitive atria were in the process of differentiating into myocardial cells. The ventricular muscle cells were the most developed cells; the least mature muscle cells were those located at the arterial and venous ends of the heart tube. The cells between the ventricle and the two ends of the heart tube showed a spectrum of developmental stages, especially with respect to the morphological development of the myofibrils. Other organelles as well as surface specializations did not permit a distinction between cells of the different regions of the heart tube. There was no striking difference in the size and shape of the developing muscle cells of the atrioventricular and bulboventricular junctions compared to the developing ventricular muscle cells. Morphologically there was no evidence to suggest that the tissue of the atrioventricular and bulboventricular rings was specialized or different from any of the other segments of the single heart tube of the embryonic ferret. | [
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10,004,276 | VIP (vasoactive intestinal polypeptide)--immunoreactive innervation of the portal vein. | [
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0.03795... |
10,004,277 | Nerve fibres displaying immunoreactivity for vasoactive intestinal polypeptide (VIP) were found in the wall of the portal vein in cats, guinea pigs, rats and mice. In whole-mount preparations a sparse network of VIP fibres was seen in the vessel wall. Electrical field stimulation of the rat portal vein in vitro caused a significant release of VIP. The results suggest that VIP ergic nerve fibres play a role in the regulation of portal blood flow. | [
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10,004,278 | Comparison between temperature-induced changes and effects caused by dark/light adaptation in the eyes of two species of Antarctic crustaceans. | [
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10,004,279 | The amphipod, Orchomene plebs, and the isopod, Glyptonotus antarcticus, both adapted to live in seawater of a temperature of -2 degree to 0 degree C, were kept for 7h at the unphysiologically high temperature of +10 degree C. Temperature elevation appeared to mimic light adaptation with regard to the position of the screening pigment granules within the visual cells, but not with respect to ultrastructural changes in the microvillar array of the rhabdom, i.e. the visual membranes. Cellular metabolism, membranous fatty acid composition, and ion fluxes, all known to be readily affected by an increase in temperature, are thought to be responsible for the observed effects. Pigment granules could possibly cause an elevation of intracellular temperatures due to the fact that they are dark and dissipate absorbed energy as heat. | [
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10,004,280 | Ultrastructural study of the epithelial mucous cells in lizards (Lacertilia). | [
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10,004,281 | An ultrastructural study of the mucous cells of the intestinal epithelium of four lacertilian species (Lacerta lepida, Lacerta hispanica, Psammodromus algirus and Acanthodactylus erythrurus) is here reported. Two types of mucous cells have been found in these species: common mucous cells and granular mucous cells. Immature and mature forms of both types have been observed. The common mucous cells or typical goblet cells have the same characteristics in all four species. The granules of the granular mucous cells of the two species of lacerta are similar but differ from those of the other two species. | [
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10,004,282 | Transmission and scanning electron-microscopic observations on tanycytes in the mediobasal hypothalamus and the median eminence of adrenalectomized rats. | [
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0.02831515... |
10,004,283 | Tanycytes in the median eminence (ME) of the rat exhibit morphological features suggesting their possible participation in transport phenomena. After adrenalectomy, which modifies the hypothalamo-hypophyseal axis, they undergo morphological changes characterized by an accumulation of lipid droplets, an increased number of bleb-like protrusions at their apex, as well as an increased pinocytosis of intraventricularly injected horseradish peroxidase (HRP). In addition, after adrenalectomy an increased number of vacuoles appears at the level of the tubero-infundibular sulci. Their intracellular location in the tanycytes is demonstrated by an intraventricular injection of HRP. The significance of these vacuoles is discussed in relation to the hydroelectrolytic modifications associated with the state of adrenalectomy. | [
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0.0355... |
10,004,284 | Phagocytosis of erythrocytes in the subarachnoid space at spinal nerve exits. | [
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0.046611... |
10,004,285 | After intracisternal injection of heparinised autologous blood in cats, spinal nerve exits (SNE) of the subarachnoid space (SAS) were examined by scanning and transmission electron microscopy. Phagocytes, erythrocytes and erythrophages (= macrophages which had phagocytosed red blood cells) were found at SNE. Some lining cells of the SAS had retracted from the adjacent cells and had rounded up. Cells which formed an integral part of the subarachnoid lining cells also had phagocytosed erythrocytes. Debris of an exhausted erythrophage was phagocytosed by other macrophages. Finally the observation has been made that erythrophages are capable of leaving the SAS actively by migrating through the layer of lining cells, thus getting into the leptomeningeal connective tissue space. | [
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0.06353... |
10,004,286 | The effect of ploidy and colcemid on the frequency of spontaneous transformation of cultured cells. | [
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10,004,287 | Variations in chromosome numbers and their possible relationship to the development of 8-azaguanine resistance in V79 Chinese hamster cells. | [
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10,004,288 | Further purification of an inhibitory factor for DNA synthesis in regenerating rat liver. | [
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10,004,289 | Stimulation of nucleologenesis by adenosine. | [
0.011570615693926811,
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10,004,290 | Surface activity and human blood platelet aggregation-inhibitory potency. | [
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0.03220962733030319,
0.016205046325922012,
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0.032... |
10,004,291 | Surface and interfacial activity is correlated with molecular constitution and inhibitory potency of mono- and bis(carbamoylpiperidino)alkanes and aralkanes, and of some corresponding quaternary pyridinium congeners, in ADP-induced human blood platelet aggregation. The measurements of surface and interfacial tension were carried out at concentrations and pH-values approximating those employed in the hemodynamic study. The effect of changes in chemical structure, ranging from relatively minor variations in a specific functional group to the alteration of major components in molecular constitution, was examined and interpreted in terms of contemporary theoretical chemistry. | [
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10,004,292 | Molecular interaction of acrylonitrile and potassium cyanide with rat blood. | [
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10,004,293 | The interaction of acrylonitrile (VCN) with rat blood has been investigated at the molecular level in an attempt to understand the possible mechanism of its toxicity. The results obtained were compared to those with potassium cyanide (KCN), a compound known to liberate cyanide (CN-) in biologic conditions. The radioactivity derived from K14CN was eliminated faster than that from [1-14C]VCN. Up to a maximum of 94% of 14C from VCN in erythrocytes was detected covalently bound to cytoplasmic and membrane proteins, whereas 90% of the radioactivity from KCN in erythrocytes was found in the heme fraction of hemoglobin. Determination of specific activity showed that binding occurred more in vivo than in vitro which indicated that the VCN molecule was bioactivated inside erythrocytes. These results indicate that KCN interacts mainly through CN- liberation and binding to heme, whereas VCN, which binds to cytoplasmic and membrane proteins, may cause damage to red cells by mechanisms other than release of CN-. | [
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0.09... |
10,004,294 | Fungal oxidation of 3-methylcholanthrene: formation of proximate carcinogenic metabolites of 3-methylcholanthrene. | [
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10,004,295 | The filamentous fungus, Cunninghamella elegans, was found to metabolize the potent carcinogen, 3-methylcholanthrene (3-MC) to 1-hydroxy-3-MC, 2-hydroxy-3-MC, 1-keto-3-MC, 2-keto-3-MC and trans-9,10-dihydrodiols of 1-hydroxy-3-MC. In addition several unidentified derivatives of 3-MC were found. The metabolites formed were separated by high pressure liquid chromatography (HPLC) and identified by comparison of retention times, absorbance, fluorescence and mass spectra with those of synthetic standards. Incubation of (+/-)-1-hydroxy-3-MC and (+/-)-2-hydroxy-3-MC with cells of C. elegans indicated that 1-hydroxy-3-MC is metabolized to form diasteromerically related trans-9,10-dihydrodiols of 1-hydroxy-3-MC. Experiments with 3-[14C]MC showed that over a 48-h period, 8.7% of the hydrocarbon was oxidized to organic solvent-soluble metabolic products. Most of the metabolites were polar products, some of which co-chromatographed with trans-9,10-dihydrodiols of 1-hydroxy-3-MC. The results show that C. elegans has the ability to oxidize 3-MC to metabolites that have been implicated as proximate carcinogenic forms of 3-MC in higher organisms. | [
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10,004,296 | Chromatographic resolution of amino acid adducts of aliphatic halides. | [
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0.013244511559605598,
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10,004,297 | Numerous xenobiotics are known to be bioactivated and to covalently and to proteins, but the resulting amino acid adducts (AAAs) are unknown. In this study the AAAs of twelve 14C-labeled aliphatic halides were examined after formation in an in vitro microsomal system. After exhaustive solvent extraction of the precipitated microsomal protein, the AAAs were isolated by Pronase digestion, followed by filtration through a 500 mol. wt. exclusion membrane. The liberated AAAs were applied to a constant flow DC-4A cation exchange column, resolved by stepwise buffer elution, collected and counted for radioactivity. Column recovery for applied radioactivity was 100 +/- 4%. Generally, 1-4 different AAAs (defined by eluting radioactivity) were resolved, with each organohalogen displaying a characteristic elution profile. Methyl iodide, trichloroethylene and 1,2-dichloroethylene had a single major AAA while bromotrichloromethane, 1,2-dibromoethane, 1,1,1-trichloroethane, 1,2-dichloroethane, 1,1,2-trichloroethane, 2-bromo-2-chloro-1,1,1-trifluoroethane, chloroform and carbon tetrachloride had up to 4 AAAs or more, indicating combinations of binding site(s) and reactive intermediate(s). The single AAA formed following incubation of methyl iodide with the microsomes was identified as S-methylcysteine. Thus, this method appears capable of resolving binding sites and is the initial isolation step for identifying specific adducts to proteins. | [
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0.0990482... |
10,004,298 | Stereoselective metabolism of the optical isomers of trans-1,2-dihydroxy-1,2-dihydrophenanthrene to bay-region diol epoxides by rat liver microsomes. | [
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0.0110... |
10,004,299 | Potential identification of chemical carcinogens in a viral transformation system. | [
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0.021034978330135345,
0.0707598328590393,
0.0150245... |
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