Does care exclude cure in palliative care?
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Adenocarcinoma, Mucinous↗
Biomedical subjects
J Epstein
Publications and source records attributed to J Epstein.
Prevention of graft-versus-host disease in allogeneic bone marrow transplantation by pretreatment with 2'-deoxycoformycin.
Germ-free mice were used as a model for acute graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation (BMT). C3H/He recipients of DBA/2 cells showed typical symptoms of acute GVHD and died within 8 days. Incubation of the cells with 10 microM 2'-deoxycoformycin (2dCF) + 100 microM deoxyadenosine (dAdo) for 1 h inhibited all T-cell functions as well as T-cell-dependent B-cell functions, but had no effect on B-cell functions that are T-cell independent, nor on the hemopoietic stem cells (CFU-S). Recipients of allogeneic cells that had been incubated with 2dCF + dAdo for 1 h prior to inoculation showed no signs, gross or histological, of acute or chronic GVHD up to 15 months after transplantation. The recovery patterns of the blood and bone marrow were not affected by the treatment, and were similar to those of recipients of treated and untreated syngeneic cells.
Animals↗
Chromosome 13 homozygosity in osteosarcoma without retinoblastoma.
We provide evidence that some human osteosarcomas arise subsequent to the development of homozygosity at loci on the long arm of chromosome 13. The resulting chromosome 13q homozygosity allows the phenotypic expression of any recessive allele on that chromosome. Clinical evidence suggests that it is the retinoblastoma locus within 13q14 that is involved in the formation of these bone tumors.
Alleles↗
Effects of busulfan on the DNA of HL-60 cells as a drug sensitivity assay.
We evaluated the formation of DNA-DNA cross links by busulfan as an assay for determining the sensitivity of cells to the drug. HL-60 cells were incubated with busulfan and the effects of the drug on cell growth were compared with the effects of the drug on the alkaline elution pattern of the DNA. While incubation with 100 micrograms/ml for 1 h inhibited cell growth by 50%, drug concentrations of up to 500 micrograms/ml had no effect on the elution pattern of the DNA.
Busulfan↗
Plasma adriamycin levels during remission induction therapy: RIA versus HPLC.
Plasma concentrations of adriamycin and adriamycinol were measured in patients with acute nonlymphocytic leukemia during remission induction therapy with araC adriamycin and cytosine arabinoside. Blood samples were analyzed at 10 min, 1, 3, 6 and 24 hrs after the end of the first, second and third daily injection of adriamycin, using high pressure liquid chromatography and a commercially available radioimmuno assay. Overall, 65 samples were compared, with the correlation coefficient r = 0.765-0.920 for the different time points. The combined correlation coefficient for 57 samples was 0.853. These correlations were significant at the p = 0.005 level.
Chromatography, High Pressure Liquid↗
Effects of salt loading during exercise in a hot dry climate.
Strenuous work or sports activities in a hot environment can cause significant fluid and salt losses due to excessive sweating. Fluid replacement is commonly accepted to be beneficial, but controversy surrounds the necessity of adding salt to the dietary intake in hot climates. Five healthy young men participated in a self-controlled experiment designed to investigate the effects of salt loading on acclimatized people exercising under controlled laboratory conditions. The additional salt ingestion was found to cause an increase in body weight, rectal temperature, heart rate, urinary sodium and potassium concentrations and in the total amounts of sodium and chloride excreted in urine during the exercise. Furthermore, it decreased plasma aldosterone level and sweat chloride excretion, but did not affect fluid intake, urine output, sweat rate, skin temperature, excretion of sodium and potassium in sweat or urinary potassium content and chloride concentration. Neither did the additional salt intake affect plasma electrolyte levels, renin activity or acid base balance. It is concluded that acclimatized people living in a hot dry climate need no supplementary salt to their daily dietary intake while engaging in physical exercise or sports activities up to two hours a day. Salt loading has no beneficial effects in these conditions and may even be hazardous.
Acclimatization↗
Characterization of human uveal melanoma cells by phosphorus 31 nuclear magnetic resonance spectroscopy.
We performed experiments to determine the potential usefulness of nuclear magnetic resonance spectra in the diagnosis and follow-up of ocular melanoma. High-resolution phosphorus 31 nuclear magnetic resonance spectra at 109.3 MHz were obtained for human uveal melanoma, Greene hamster melanoma, and normal human diploid fibroblast cells. Phosphate metabolites were identified and their concentrations were shown to vary among the different cell lines. Uveal melanoma cells contain unusually high concentrations of the phospholipid metabolite phosphorylcholine and the phosphodiesters glycerol 3-phosphoryl choline and glycerol 3-phosphoryl ethanolamine. Baseline data are thus provided for studies of the effect of various treatment modalities on uveal melanoma. These initial results suggest that the data provided by high-resolution phosphorus 31 nuclear magnetic resonance spectra can provide useful diagnostic and follow-up data with respect to ocular melanoma.
Adenosine Triphosphate↗
Expression of an ouabain resistance gene in transfected cells. Ouabain treatment induces a K+-transport system.
We have investigated the expression of a cloned mouse gene which confers ouabain resistance to African green monkey kidney (CV1) cells. CV1 cells carrying the transfected ouabain resistance (ouaR) gene express an ouabain-inducible K+-transport system. This K+-transport system is not a normal (Na,K)-ATPase since plasma membranes prepared from the transfected cells have significantly reduced Na+-stimulated ATPase activity. RNA sequences homologous to the transfected gene are observed in abundance only following exposure of transfectants to ouabain. The small size of the message induced (1.2 kilobases) also argues that the gene does not code for the alpha-subunit of the (Na,K)-ATPase. Ouabain-treated transfected cells maintain an internal [K+] of 113 mM; a level close to the 139 mM of control cells. However, ouabain-treated transfectants exhibit an internal [Na+] of 61 mM, which is 3-6 times the level in untreated cells (11-21 mM). These results suggest: ouabain resistance can be conferred by a gene which codes for an ouabain-inducible K+-transport system; induction of this transport system by ouabain is due to increased levels of mRNA coded for by the ouabain resistance gene; and the ouabain resistance gene does not encode for the alpha-subunit of the (Na,K)-ATPase.
Animals↗
Preparation of individual human diploid fibroblasts and study of ion transport.
A method for analyzing individual mammalian cells with electron probe microanalysis has been developed using human diploid fibroblasts. Cells were grown on the same support that is used for experimental manipulations and analysis. Steady-state cation and anion concentrations and kinetic processes during experimental perturbations could be measured on populations of less than 1,000 cells. Human diploid fibroblasts in normal tissue culture medium had the following intracellular concentrations (in mM): K, 168; Na, 25.0; Cl, 51.2; P, 84.1; S, 16.5; Ca, 6.04; and Mg, 10.0. The ratios of K to Na were equivalent when measured in the nuclear or cytoplasmic area of the cells. Serum in the incubation medium was found to increase the cellular effective permeability to Na by a factor of 2.5, while leaving the effective permeability to K unchanged. When returned to control medium after 7 h of incubation in K-free medium, the cells recovered normal K/Na in less than 1 h. In some experiments the coupling ratio of the ouabain-inhibitable cellular transport of Na to K was 3:2 and the ratio of Cl to K was 1:2. The sum of intracellular content (Na + K) (an estimate of cellular volume) did not change when the cells were placed in K-free medium and increased by less than 30% after ouabain treatment. After 5-7 h of ouabain treatment or of incubation in K-free medium, long after the intracellular K had been replaced by Na, the cellular chloride content had not changed significantly.
Biological Transport↗
Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection.
Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. However, 20 patients had abnormal serologic profiles specific for Epstein-Barr virus shown by significantly elevated titers of antibodies to the viral capsid antigen or early antigen, or by a deficiency of late-appearing antibodies. In 11 of 15 patients tested, circulating immune complexes were found. Circulating interferon was not found in 18 patients tested, but the activity of 2-5 oligoadenylate synthetase, an interferon-induced enzyme, was increased in 5 patients studied. Of 19 patients, 18 had persisting suppressor T-cell activity typically found in patients recovering from acute infectious mononucleosis. We believe that the Epstein-Barr virus may be associated with chronic illness in adults.
Adolescent↗
Inhibition of adenosine deaminase and purine nucleoside phosphorylase and T-cell function in germfree mice and human peripheral blood.
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Adenosine Deaminase↗
Histological and immunological evaluation of gnotobiotic C3H/He mice following i.v. administration of 8-aminoguanosine and 2'deoxyguanosine.
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Animals↗
Inositol 1,4,5-trisphosphate stimulates phosphorylation of a 62,000-dalton protein in monkey fibroblast and bovine brain cell lysates.
Inositol 1,4,5-trisphosphate (IP3) is produced in cells as a breakdown product of the diphosphorylated form of phosphatidylinositol, phosphatidylinositol 4,5-bisphosphate. Stimulated breakdown of phosphoinositides has been correlated with a wide variety of hormonal stimuli which mobilize intracellular calcium, and IP3 has recently been found to cause calcium release from intracellular stores, thus implicating it as a second messenger in hormonal stimulation. In this paper we have examined the effect of IP3 on protein phosphorylation, and have found that IP3 stimulates phosphorylation of a 62-kDa protein in cell lysates made from cultured monkey fibroblasts and from bovine brain. Fifty per cent maximal stimulation of phosphorylation of this protein occurred at 2.5 X 10(-7) M IP3. Other inositol phosphates (inositol 1,4-bisphosphate, inositol 1-phosphate, inositol hexaphosphate, and myo-inositol) had no effect on protein phosphorylation at 10(-6)M, although inositol 1,4-bisphosphate at higher concentrations enhanced phosphorylation of the 62-kDa protein in brain lysates. The IP3-stimulated phosphorylation was calcium-independent and did not appear to result from inhibition of an endogenous protein phosphatase. We suggest that IP3, like other second messengers, acts as a protein kinase regulator.
Animals↗
Herpesvirus infections in the acquired immune deficiency syndrome.
Herpesvirus infections were studied in persons with or at risk for the acquired immune deficiency syndrome (AIDS). The infections diagnosed were as follows: patients with AIDS, cytomegalovirus (CMV) in 34 of 34, Epstein-Barr virus (EBV) in 33 of 34, herpes simplex viruses (HSV) in eight of 34, and varicella zoster virus in four of 34; patients with chronic lymphadenopathy syndrome, CMV in eight of nine and EBV in nine of nine; in healthy homosexual men, CMV in five of 13 and EBV in seven of eight. Cytomegalovirus infections were frequently related to disease and death. Herpesvirus infections are frequent causes of serious diseases in AIDS. The prevalence of EBV and CMV infections in AIDS and the chronic lymphadenopathy syndrome may be the result of an important interaction between these viruses and the cause of AIDS.
Acquired Immunodeficiency Syndrome↗
Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia.
Plasma adriamycin and adriamycinol levels were measured in 45 patients with acute nonlymphocytic leukemia 3 h after the drug was administered. A wide range of levels as found. Plasma levels increased after the administration of each of the three daily doses of the drug. High plasma levels were associated with both death during remission induction therapy and, for patients who entered remission, long remissions.
Acute Disease↗
Lack of bronchomotor response to up to 3 ppm formaldehyde in subjects with asthma.
A study was undertaken to determine whether exposure to concentrations of formaldehyde occasionally encountered in polluted indoor air would cause bronchoconstriction in subjects with mild asthma. In seven subjects the increase in specific airways resistance (SRaw) caused by inhalation of 1 ppm formaldehyde for 10 min was compared with the response caused by inhalation of formaldehyde-free air. Also, the increase in SRaw caused by inhalation of 1 and 3 ppm formaldehyde during moderate exercise for 10 min was compared with the response caused by inhalation of formaldehyde-free air during exercise for 10 min. Inhalation of formaldehyde at rest and during exercise did not cause a significant increase in SRaw in the subjects. It is concluded that brief exposure to these concentrations of formaldehyde, even in association with moderate exercise, is unlikely by itself to cause significant bronchoconstriction in most subjects with mild asthma.
Adolescent↗
Variable inhibition of histamine-induced bronchoconstriction by atropine in subjects with asthma.
To determine whether treatment with atropine causes dose-dependent inhibition of histamine-induced bronchoconstriction, we constructed dose-response curves to inhaled histamine after inhalation of placebo and 0.26 and 2.08 mg of atropine in eight subjects with mild asthma. Both doses of atropine significantly inhibited histamine-induced bronchoconstriction, and 2.08 mg caused significantly greater inhibition than 0.26 mg. Baseline specific airway resistance was significantly reduced by both doses of atropine but was no different after 2.08 mg than after 0.26 mg. There were considerable differences in the efficacy of atropine among individuals. We conclude that atropine causes dose-dependent inhibition of histamine-induced bronchoconstriction and that this effect is not merely a function of the atropine-induced in baseline airway caliber. The large magnitude of the atropine effect in some subjects and the small magnitude of the effect in others suggest that there is variability in the degree of involvement of muscarinic mechanisms in the exaggerated bronchomotor response to histamine in asthmatic subjects.
Adult↗
Inhibition of DNA synthesis by cytosine arabinoside: relation to response of acute non-lymphocytic leukemia to remission induction therapy and to stage of the disease.
The sensitivity of leukemic marrow cell DNA synthesis to cytosine arabinoside (araC) exposure in vitro was studied in specimens obtained from patients with acute non-lymphocytic leukemia. Cells from patients who had been treated with araC in the past were more likely to be resistant to the effect of araC on DNA synthesis than cells obtained from patients who had not been so-treated previously. Resistance to the effects of araC on DNA synthesis was associated with the failure of high-dose araC therapy to induce remissions in relapsed patients, whereas remission induction failure in previously untreated patients was not associated with araC resistance.
Acute Disease↗