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Biomedical subjects

J Epstein

Publications and source records attributed to J Epstein.

At least 163 records · Page 9Linked to original sources

Prediction of response of acute nonlymphocytic leukaemia to therapy with 'high dose' cytosine arabinoside.

The Leukemia Intergroup Study has treated 110 patients with acute nonlymphocytic leukaemia with 'high dose' cytosine arabinoside remission induction therapy and studied the factors which were related to the outcome of therapy. With respect to death during remission induction therapy, only patient age was of prognostic significance. Treatment failure due to resistant leukaemia was associated with a high pretherapy leukaemic cell mass, the presence of few cells in S phase, and insensitivity of DNA synthesis to cytosine arabinoside. If, after 6 d of therapy, more than 40% of the marrow cells were leukaemic, the patient almost invariably failed to enter complete remission because of persistent leukaemia. Simultaneous consideration of the pretherapy labelling index and the per cent abnormal cells in the day 6 marrow permitted a distinction to be made between almost all patients who would enter remission or fail therapy because of persistent leukaemia.

Age Factors↗

Interaction of sulfur dioxide and dry cold air in causing bronchoconstriction in asthmatic subjects.

To determine whether sulfur dioxide and airway cooling and drying interact in causing bronchoconstriction in persons who have asthma, we measured specific airway resistance in seven asthmatic subjects before and after they performed voluntary eucapnic hyperpnea for 3 min breathing four different gas mixtures. The mixtures, which the subjects breathed through a mouthpiece in random order on 4 different days, were 1) humidified room-temperature air, 2) humidified room-temperature air containing 0.5 ppm SO2, 3) cold dry air, and 4) cold dry air containing 0.5 ppm SO2. Each subject breathed at a rate and depth known from preliminary studies to cause little or no bronchoconstriction when that subject inhaled 0.5 ppm SO2 in humidified room-temperature air or cold dry air. When given independently in the blinded study, 0.5 ppm SO2 or cold dry air again caused insignificant bronchoconstriction, but when given together the two stimuli caused significant bronchoconstriction, as indicated by an increase in specific airway resistance from 6.94 +/- 2.85 to 22.35 +/- 10.28 l X cmH2O X l-1 X s (mean +/- SD) (P less than 0.001). thus airway cooling and/or drying increases the bronchoconstriction induced by inhaled SO2 in persons who have asthma. This increase suggests that persons who have asthma may be more sensitive to the bronchoconstrictor effects of ambient SO2 in cold dry environments than in warm moist environments.

Adult↗

Protection of normal hematopoietic stem cells from the toxicity of purine base analogs: in vivo application.

Normal murine bone marrow cells were incubated with adenosine (100 microM) for 2 hrs followed by the addition of 6-thioguanine (6-TG) (0.3 and 1.0 microgram/ml) for 1, 24, and 48 hrs, and the survival of the committed stem cells (CFUc) and pluripotential stem cells (CFUs) was compared to the survival of CFUc and CFUs which were similarly incubated without adenosine. When 0.3 microgram/ml of 6-TG was used, preincubation with adenosine increased the survival of CFUc from 25% to 80% and from 14% to 36% for 24- and 48-hr incubations, respectively (P less than or equal to 0.005). For 1 microgram/ml of 6-TG, pretreatment with adenosine increased survival from from 11% to 69% and from 5% to 24%, respectively, for 24- and 48-hr incubations (P less than or equal to 0.0005). Adenosine had a similar effect on CFUs (P less than or equal to 0.03). This effect was not seen when equimolar concentrations of hypoxanthine, inosine, or adenine were substituted for adenosine. Inoculation of adenosine into mice (500 mg/kg of body weight) 1 hr prior to injection of lethal doses of 6-TG (50 mg/kg) increased the survival of the mice from 10% to 100% and from 20% to 80%, respectively, using two administration schedules. This effect of adenosine, which, as has been previously shown, is the result of the depletion of cellular phosphoribosyl pyrophosphate pools, is potentially useful for the selective protection of normal hematopoietic cells from the toxicity of purine analogs which require activation via a phosphoribosyl pyrophosphate-dependent reaction, while therapeutic effects are produced against malignant tissue.

Adenosine↗

Genital herpes infection in pregnant women near term.

A study of 215 middle income, predominantly white, suburban women for herpes simplex virus infection revealed that ten (4.6%) had positive herpes cultures near term and thus were at risk for transmission of herpes simplex virus to their newborn. Eight of these women had a previous history of herpes simplex virus infection, and seven of the eight had lesions suggestive of herpes simplex virus at the time of study. Only one patient had lesions at delivery. On the basis of past history of genital herpes or partners with herpes, 25 of the 215 women were at high risk for genital herpes near term. Thus, careful questioning identified a high-risk group of 25 patients in which eight (32%) were shedding virus near term, and this group included the majority (eight of ten) of the herpes simplex virus-infected women in the study population. There were no cases of neonatal herpes in the children born from the 215 pregnancies.

Adolescent↗

Establishment of cell lines of uveal melanoma. Methodology and characteristics.

Six continuous cell lines have been established from choroidal and ciliary body melanomas. These lines have been maintained in culture for at least 100 in vitro population doublings for periods over 1 year. They were established initially using a human diploid fibroblast strain MRC-5 as a feeder layer. Cells were grown in Ham's F-12 medium containing fetal bovine and horse sera and supplemented with glucose, cholera toxin, and epidermal growth factor. Culture doubling times ranged from 72-96 hr; cloning efficiencies ranged from 1-5% in the absence of a feeder layer. Six cell lines were studied in detail by electron microscopy, and all were found to have evidence of melanosomes and/or premelanosomes. The morphology of the cells was characteristic of melanomas as defined by the Callender classification, with cell types ranging from spindle A to epithelioid. Karyotypic studies revealed the presence of only human chromosomes with modal numbers ranging from 48-54 in the different lines.

Adult↗

Tolerance to sulfur dioxide-induced bronchoconstriction in subjects with asthma.

A study to determine whether the bronchoconstriction induced by low concentration of sulfur dioxide in subjects with asthma decreases with repeated exposure was undertaken. Eight subjects with asthma performed 3 min of voluntary eucapnic hyperpnea with 0.5 ppm of SO2 in humidified filtered air three times at 30-min intervals and we measured specific airway resistance (SRaw) before and after each period of hyperpnea. Specific airway resistance increased significantly more after the first exposure to SO2 [(from 7.6 +/- 1.7 to 15.5 +/- 2.0 L x cm H2O/liter/sec (mean +/- SEM)] than after the second (from 8.1 +/- 1.3 to 10.8 +/- 1.6) or third (from 7.6 +/- 1.6 to 10.1 +/- 1.9) exposures (P less than 0.025). When seven subjects repeated hyperpnea with SO2 24 hr and 7 days later, SRaw increased as much as it had after the first exposure (from 8.2 +/- 2.5 to 15.5 +/- 4.5 at 24 hr and from 6.6 +/- 1.4 to 15.4 +/- 2.1 at 7 days). In four subjects repeated exposure to SO2 caused short-term inhibition of the bronchomotor response to SO2 but did not inhibit the bronchomotor response to histamine aerosol. It was concluded that repeated exposures to a low concentration of SO2 over a short period (on 1 day) can induce tolerance to the bronchomotor effects of SO2 in subjects with asthma. Tolerance to the bronchomotor effects of SO2 is not caused by decreased responsiveness of airway smooth muscle or a generalized decrease in the responsiveness of vagal reflex pathways since the bronchomotor response to histamine is preserved.

Adult↗

A non-clonogenic assay for the determination of the sensitivity of leukemic cells to chemotherapeutic agents.

A new method for measuring the effects of chemotherapeutic agents on leukemic cells has been developed. In this method tritiated thymidine [( 3H]-TdR) is used to determine the surviving proportion of leukemic cells which are stimulated to proliferate by colony-stimulating factor (CSF). The effects of four antileukemia drugs on bone marrow cells from 20 AML patients were studied using this method and the results correlated well with the effects of the drugs on the CFUc, which were studied simultaneously. Using the liquid culture method drug effects were measured on five bone marrow specimens which failed to clone in the CFUc assay as well as on three specimens which produced too few colonies/clusters to allow estimation of drug effects.

Aclarubicin↗

Effect of route of atropine delivery on bronchospasm from cold air and methacholine.

We undertook a study to determine whether the apparent disparity between the dose of inhaled atropine required to inhibit the bronchoconstriction induced by inhaled methacholine and the dose required to inhibit the bronchoconstriction induced by eucapnic hyperpnea with cold air is a function of the route of administration of atropine. In six subjects with asthma, we constructed dose-response curves to inhaled methacholine and to eucapnic hyperpnea with cold air after treatment with inhaled atropine (0.5 mg delivered) and intravenous placebo, with inhaled placebo and intravenous atropine (0.5 mg injected), and with inhaled and intravenous placebos. Atropine by either route shifted the dose-response curves to both cold air and to methacholine to the right. In every subject, however, inhaled atropine caused a markedly greater rightward shift of the inhaled methacholine dose-response curve than did intravenous atropine, whereas inhaled and intravenous atropine had similar effects on the cold air dose-response curve. These findings suggest that the apparent disparity between the doses of atropine required to inhibit methacholine- and cold air-induced bronchoconstriction may be a function of the route of administration of atropine and thus does not imply a nonmuscarinic action of atropine. The findings support the view that cold air causes bronchoconstriction via muscarinic pathways.

Adult↗

Effect of exercise rate and route of inhalation on sulfur-dioxide-induced bronchoconstriction in asthmatic subjects.

Nine asthmatic subjects exercised at low, moderate, and high work rates on a cycle ergometer while breathing filtered, humidified air with or without 0.5 ppm of sulfur dioxide (SO2) in a double-blind study. Subjects first performed these experiments breathing through a mouthpiece while wearing a noseclip (oral breathing) and then repeated the experiments breathing through a facemask that separated and permitted independent measurement of oral and nasal air flow (oronasal breathing). We determined specific airway resistance before and after exercise by body plethysmography. Inhaled by mouthpiece, 0.5 ppm So2 caused bronchoconstriction at moderate and high but not at low work rates. There was a dose-response relationship between the work rate performed and the degree of bronchoconstriction induced. Inhaled oronasally, 0.5 ppm SO2 caused bronchoconstriction only at the high work rate. These findings demonstrate that So2-induced bronchoconstriction is dependent on the work rate of exercise during exposure, that oronasal breathing is only partially effective in preventing the bronchoconstriction observed with oral breathing, and that oronasal breathing is less effective in preventing bronchoconstriction with high than with moderate exercise at this concentration of SO2.

Adult↗

Sulfur dioxide-induced bronchoconstriction in freely breathing, exercising, asthmatic subjects.

The purpose of this study was to determine whether 0.50 ppm sulfur dioxide (SO2) in filtered air causes bronchoconstriction in freely breathing asthmatic subjects exercising at a moderately heavy work rate. Ten volunteers who had mild asthma breathed air containing no SO2 or containing 0.50 ppm SO2 In an exposure chamber as they exercised for 5 min on a cycle ergometer at a work rate of 750 kilopond meters/min (about 125 watts). We determined their specific airway resistance by body plethysmography before and after exercise. Specific airway resistance increased by 13.55 +/- 9.18 cm H2O X s (mean +/- SD) when subjects exercised and breathed 0.50 ppm SO2 but only by 2.24 +/- 2.34 when they exercised and breathed air without SO2 (p less than 0.005). Thus, 0.50 ppm SO2 causes significant bronchoconstriction in freely breathing asthmatics during moderately heavy exercise.

Adult↗

The effect of prostaglandins on the multiplication and cell-to-cell spread of herpes simplex virus type 2 in vitro.

Herpes simplex virus type 2 (HSV-2) after infecting an individual has the ability to remain latent in nervous tissues. The factors that control herpesvirus infection, latency, and reactivation are poorly understood. Fever, menstruation, emotional stress, exposure to sunlight, and surgical resection have been associated with activation of latent herpes. The situations which activate latent herpes are associated with a local or systemic rise in prostaglandins. The data presented show that prostaglandin F2 alpha (PGF2 alpha) and E2 (PGE2) enhanced cell-to-cell spread of HSV-2 in an in vitro model. Ibuprofen, a prostaglandin inhibitor, suppressed HSV-2 multiplication as well as cell-to-cell spread. Prostaglandins may play an important role in herpesvirus infections and latency.

Dinoprost↗

SV40-transformed human cells fail to grow in zinc concentrations which permit normal human fibroblast proliferation.

Zinc is a metal known to be required for normal growth of both cells, and organisms. When normal and SV40-transformed human tumor cells are plated and grown in medium containing zinc sulfate, a significant fraction of the transformed cells fail to grow at zinc concentrations which are relatively nontoxic to the normal fibroblasts. Although cultured cells respond to certain metallic ions by increasing their metallothionein content, no difference in the ability of normal and transformed cells to produce metallothionein in response to zinc exposure could be detected, thus ruling out this mechanism as a basis for the differing abilities of the cells to grow in zinc in vitro. These results suggest that zinc may be capable of differentially regulating the growth of normal and SV40-transformed human fibroblasts.

Cell Division↗

Dose-dependent inhibition of cold air-induced bronchoconstriction by atropine.

We undertook a study to demonstrate whether inhalation of atropine could inhibit cold air-induced bronchoconstriction in a dose-dependent fashion. In seven subjects with asthma we assessed the effects of placebo and of various doses of inhaled atropine (0.13-2.08 mg) on a base-line specific airway resistance (sRaw) and on the increase in sRaw produced by 5 min of voluntary eucapnic hyperventilation with subfreezing air at -17 degrees C. We also assessed the effect of the lowest doses of atropine on the increase in sRaw produced by five breaths of 1.0% metacholine. Atropine in doses of 0.13 or 0.26 mg caused a maximal reduction in base-line sRaw and completely inhibited the effect of 1.0% methacholine on sRaw, but it did not inhibit the bronchomotor response to cold air. Higher doses of atropine did inhibit the effect of cold air on sRaw in a dose-dependent fashion. The dose of atropine required to inhibit this effect of cold air varied with the increase in sRaw produced by cold air after placebo. These results suggest that cold air causes bronchoconstriction through vagal pathways and that higher doses of antimuscarinic agents are required to inhibit vagally mediated bronchoconstriction than those required to reduce base-line airway tone or to inhibit the effects of a large dose of an inhaled muscarinic agonist.

Adult↗

Chronic lateral ankle instability: results when treated with the modified Evans procedure.

A brief discussion of etiology and diagnosis of chronic ankle instability precedes results of a follow-up study of a modified Evans procedure. Between 1974 and 1980, 29 patients with chronic ankle instability were operated on at Harrison Community Hospital. Of the patients who replied to the follow-up study, 75% reported good functional stability. Assessment of surgical results was 62.5% excellent, 25% good, 6.25% satisfactory, and 6.25% poor.

Adolescent↗

Electrostatic control of enzyme reactions: effect of ionic strength on the pKa of an essential acidic group on glucose oxidase.

The dissociation constant of an essential acidic group on the reduced form of glucose oxidase from Aspergillus niger (K4) has been found to be extremely sensitive to ionic strength. Increasing the ionic strength from 0.025 to 0.225 causes a decrease in pK4,obsd of 0.9 pH unit, from 8.2 to 7.3. Analysis of the ionic strength dependence of pK4,obsd, making the assumption that the enzyme is a homogeneously charged impenetrable sphere [Edsall, J. T., & Wyman, J. (1958) Biophysical Chemistry, Vol. 1, pp 282-289, 512-514, Academic Press, New York], predicts that the intrinsic pKa of the acidic group is 6.7 and that the charge on the protein is -78. The enzyme was titrated from its isoelectric point (pH 4.05) to pH 7.7, the pH at which the ionic strength dependence was determined. It was found to have an actual charge at that pH of -77, in remarkable agreement with the theoretical prediction. Thus, glucose oxidase exerts electrostatic control on pK4,obsd as though it were a uniformly charged sphere. The group responsible for pK4,obsd has not been identified. However, its measured delta H degrees obsd of 8.0 kcal mol-1 and delta S degrees obsd of -6.1 cal mol-1 K-1, together with its pKa of 6.7, are consistent with the group being a histidine residue.

Aspergillus niger↗