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Biomedical subjects

M Steinberg

Publications and source records attributed to M Steinberg.

At least 109 records · Page 6Linked to original sources
PubMed1987

[Human recombinant leukocyte interferon alpha-2-A in 22 cases of metastatic malignant melanoma].

Twenty-two patients with metastatic malignant melanoma received either 36 X 10(6) U (15 patients) or 18 X 10(6) U (7 patients) of human recombinant interferon alpha-2-A daily for 3 months by the intramuscular route, with progressive increase of dosage. This was followed in responders by a maintenance treatment consisting of 3 intramuscular injections per week in the same doses as those received at the end of the induction treatment. Out of 18 patients assessable for effectiveness, 1 had complete remission (7 months +) and 3 had partial response (52,61 and 82 days respectively), an overall improvement rate of 22%. The main side-effects observed were: pseudoinfluenza syndrome (100%), fatigue (100%), somnolence (95%), anorexia (90%) and haematological disorders. Dosage reduction was necessary in 13 of the 15 patients receiving 36 MU. This study shows that human recombinant interferon alpha-2-A has antitumoral activity in metastatic malignant melanoma. Other studies, notably with therapeutic combinations, are needed to determine the optimal dosage regimen of the drug and to increase its effectiveness.

Adolescent↗
PubMed1987

Accessibility of tryptophan residues in Na,K-ATPase.

The accessibility of the tryptophans in dog kidney Na,K-ATPase was studied with the technique of quenching by acrylamide. By use of a modified Stern-Volmer equation, fa, the effective fraction of tryptophans most exposed to quencher, and Ka, the effective quenching constant, were calculated. The direct Stern-Volmer plots are nonlinear under nondenaturing conditions, indicating that the tryptophan residues are unequally accessible to quencher. Modified Stern-Volmer plots revealed marked differences in the exposure of tryptophans in the E1 and E2 states. In the presence of Na or ADP, ligands that stabilize E1, these plots curve downward, indicating that the in addition to buried (unquenched) tryptophans, there is a heterogeneous class of tryptophans. In the presence of K or ouabain, conditions that favor E2, the modified Stern-Volmer plots are linear, consistent with a homogeneous population of tryptophans. Treatment with chymotrypsin to block the E1 to E2 transition results in a new set of quenching parameters which are unchanged with Na or K. Even after detergent denaturation (1% sodium dodecyl sulfate for 30 min), Stern-Volmer plots are nonlinear, and a significant fraction of tryptophan residues remain inaccessible to quencher. Denaturation with urea or guanidine HCl plus dithiothreitol increases the fraction of quenchable fluorescence even more, but still a small fraction, about 7-13%, is buried. The observed changes in exposure of the tryptophan residues would seem to account for the differences in intrinsic fluorescence seen on adding K and Na to Na,K-ATPase. The present results provide new evidence that a significant rearrangement of amino acid residues results from the E1 to E2 transition. Furthermore, a region of the molecule is inaccessible even after denaturation; this may correspond to highly hydrophobic stretches that are normally buried in the membrane.

Acrylamide↗
PubMed1987

Comparison of rates of cation release and of conformational change in dog kidney Na, K-ATPase.

1. It is now widely believed that the main rate-limiting step in the sodium-potassium pump (Na, K-ATPase) cycle is a conformational change between two forms of the dephosphoenzyme (E2 and E1) and that this change releases to the cell interior potassium ions occluded within the E2 form. 2. If this hypothesis is correct, and if occluded ions cannot be released directly from dephosphoenzyme in the E2 conformation, we should expect that, under any given conditions, the rate of release of the occluded ions would be identical with the rate of the conformational change. 3. Using the potassium congeners 86Rb, 137Cs and 204Tl, the rates of release of the occluded ions can be measured by a rapid ion-exchange technique. Using the fluorescence probes fluorescein isothiocyanate (FITC), eosin or 5-iodoacetamido-fluorescein (5-IAF), the rates of the conformational change can be measured by stopped-flow fluorimetry. 4. A comparison of the two rates in the absence of ATP showed that the rate of release of the occluded ions was usually somewhat faster than the rate of the fluorescence change. The discrepancy was probably caused by a very slow direct release of occluded ions from enzyme in the E2 form, but we cannot exclude the possibility that it is the result of systematic errors. In the presence of 5 microM-ATP, both rates were increased and there was no significant difference between them. 5. The results are compatible with the hypothesis that the same conformational change alters the fluorescence of the fluorescent probes and releases the occluded potassium congener ions.

Animals↗
PubMed1987

Difficulty in establishing diagnosis from lung biopsies and bronchial washing analysis in children with leukemia following bone marrow transplantation.

Three children developed severe respiratory distress at days +12, +11, and +11 following allogeneic bone marrow transplantation from donors. The first child was a 13-year-old Hispanic boy transplanted in relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). At day -14, a bronchial washing done for a streaky pulmonary infiltrate was negative for acid-fast bacilli. Miliary tuberculosis was discovered at postmortem examination. A second child, transplanted in remission of null-cell ALL, developed severe hypoxia and hypercarbia on day +11 but recovered fully following prolonged mechanical ventilation. An open-lung biopsy showed a pattern of nonspecific, diffuse alveolar damage compatible with respiratory distress syndrome. The third child was transplanted in remission of B-cell ALL and developed fatal fungal and cytomegalovirus pneumonia on day +12. In these latter two cases, it is likely that open-lung biopsy would have missed the diagnosis because of the uneven pulmonary involvement and multiple etiologies observed. All three children received cyclosporine, granulocyte transfusions, and multiple antimicrobials, including amphotericin B. Hyperfractioned total-body irradiation with lung shielding was used in the latter two patients.

Adolescent↗
PubMed1986

Leukemia of early infancy. Early B-cell lineage associated with t(4:11).

A case of infantile acute leukemia associated with translocation t(4:11)(q21:q23) is reported. This leukemia has a very poor prognosis, and this patient survived for only 9 months. The blast cell morphology was L1/L2 according to the FAB classification and showed a lymphoid appearance on transmission electron microscopy. The histochemical stains showed a pattern of periodic acid-Schiff positivity and variable alpha-naphtyl acetate staining. The cells were TdT-positive and surface-marker phenotyping was positive for Ia-like and B4 antigens but negative for CALLA, T-cell markers, myelocyte and monocyte markers. The leukemic cells represent a frozen state of a very early precursor, corresponding to the earliest recognizable stage of the B-cell lineage. This observation may contribute to the controversion regarding the cell origin of this unique leukemia associated with t(4:11), lymphatic versus null cell, early myeloid, or mixed, and points to the possibility of a very early B-cell lineage leukemia.

Antigens, Neoplasm↗
PubMed1986

Socio-environmental factors and lung function.

The literature was reviewed to assess whether the evidence implicating socio-environmental (SE) factors as determinants of adult lung function was sufficient to require that they be taken into account in epidemiological studies, together with other factors, such as age and smoking. In six studies involving 11,000 adults resident in the USA, France and Denmark forced expiratory volume in 1 second was related to social class and/or one of a number of other factors including education, area of residence and housing status. Trends in three other studies involving approximately 15,000 children resident in the UK and the USA were similar. The consistency of the findings makes it difficult to escape the conclusion that SE factors should be taken into account in comparisons of lung function between populations when the purpose is to assess the role of other environmental factors such as occupational exposure.

Adolescent↗
PubMed1986

Ligand binding to (Na,K)-ATPase labeled with 5-iodoacetamidofluorescein.

The equilibrium binding of sodium, potassium, and adenine nucleotides to dog kidney (Na,K)-ATPase was studied by measuring changes in the fluorescence of enzyme labeled with 5-iodoacetamidofluorescein (5-IAF). The intensity of the fluorescence emission at 520 nm of the bound fluorescein (excited at 490 nm) is increased by ATP, adenyl-5'-yl imidodiphosphate (AMP-PNP), ADP (but not AMP), and Na+, and decreased by K+, Rb+, NH+4, and LI+. Thus the fluorescence effects correlate with the ability of these groups of ligands to stabilize E1 and E2 conformations, respectively. The Na+-induced increase in fluorescence has two components: a slow, high-affinity increase of approximately 7% (K0.5 = 0.16 mM) with positive cooperativity; and a large (approximately 15%), rapid, low-affinity (K0.5 = 34 mM) increase that is not cooperative. The K0.5 for the high-affinity effect is decreased by oligomycin and increased by K+. ATP effects on the fluorescence follow Michaelis-Menten kinetics and are of high affinity (K0.5 = 0.12 microM); K+ increases the K0.5 for ATP, AMP-PNP, and ADP but does not induce cooperative behavior. K+ itself decreases the fluorescence signal by about 9%, with high affinity (K0.5 = 5 microM), showing Michaelis-menten behavior in the absence of other ligands, while with ATP, Na+, or Mg2+ present, K+ effects are cooperative and of lower affinity.

Adenosine Triphosphate↗
PubMed1986

5-Iodoacetamidofluorescein-labeled (Na,K)-ATPase. Steady-state fluorescence during turnover.

The fluorescence of (Na,K)-ATPase labeled with 5-iodoacetamidofluorescein was studied under turnover conditions. At 4 degrees C the hydrolysis of ATP is slowed sufficiently to permit study of the effects of Na+, K+, and ATP on the steady-state intermediates. With Na+ and Mg2+ (Na-ATPase conditions), addition of ATP produces a 7% drop in signal that reverts back to the initial, high fluorescence after a steady state of several minutes. K-sensitive phosphoenzyme is formed under these conditions, indicating that the fluorescence signal during the steady state is associated with E2P. Under (Na,K)-ATPase conditions (Na+, K+, Mg2+), micromolar ATP produces a steady-state signal that is 25% lower than the initial fluorescence, with no detectable phosphoenzyme formed. This low-fluorescence intermediate, which is also formed by adding K+ to enzyme in the Na-ATPase steady state described above, resembles the state produced by adding K+ directly to enzyme under equilibrium conditions, i.e. E2K. The K0.5(K+) for the fluorescence decrease and for keeping the enzyme dephosphorylated are nearly identical, indicating that the fluorescence change accompanies K+-dependent dephosphorylation. High ATP increases the steady-state fluorescence during the (Na,K)-ATPase reaction; while oligomycin produces still another steady-state fluorescent intermediate. These last two intermediates may be associated with the formation of E2P and E1P, respectively.

Adenosine Triphosphate↗
PubMed1986

Magnetic resonance imaging of avascular necrosis of the femoral head.

This study investigates the role of magnetic resonance imaging (MR) in identifying avascular necrosis (AVN) of the femoral head and in monitoring its therapy. The detection of AVN, particularly in its early stages, is imperative to give therapeutic intervention the best opportunity for successful management. The results of magnetic resonance imaging are compared with those of the standard diagnostic modalities in evaluation of patients with the lesion. Examinations were performed at 0.12T with a repetition time (TR) of 143 ms and times to echo (TE's) of 10 or 20 ms. This study represents a retrospective review of 90 hips which were examined in 45 consecutive patients. Of these, 52 hips were biopsied as part of treatment. MR was shown to be sensitive in the detection of AVN. Comparison of MR with radionuclide imaging showed comparable sensitivity and specificity. MR was also noted to be sensitive in the detection of early AVN. Preliminary results suggest that MR can monitor treatment of the affected hip, and may even be able to predict patient response to therapy. Although further work is necessary to determine the role of MR in the evaluation of the patient presenting with hip pain, MR is a sensitive method in detecting AVN and in monitoring its course in patients suspected of having the disease.

Adult↗
PubMed1986

Fluoride and beryllium interact with the (Na + K)-dependent ATPase as analogs of phosphate.

Fluoride irreversibly inhibits the (Na + K)-ATPase, and this inactivation requires divalent cations (Mg2+, Mn2+, or Ca2+), is augmented by K+, but is diminished by Na+ and by ATP. Prior incubation with the aluminum chelator deferoxamine markedly slows inactivation, whereas adding 1 microM AlCl3 speeds it, consistent with AlF-4 being the active species. Prior incubation of the enzyme with vanadate also blocks inactivation by fluoride added subsequently. Fluoride stimulates ouabain binding to the enzyme, and thus the analogy between AlF-4 and both orthophosphate and orthovanadate is reflected not only in the similar dependence on specific ligands for their enzyme interactions and their apparent competition for the same sites, but also in their common ability to promote ouabain binding. Beryllium also irreversibly inhibits the enzyme, and this inactivation again requires divalent cations, is augmented by K+, but is diminished by Na+ and by ATP. Similarly, prior incubation of the enzyme with vanadate blocks inactivation by beryllium added subsequently. Inactivation by beryllium, however, does not require a halide, and, unlike inactivation by fluoride, increases at basic pHs. These observations suggest that beryllium, as beryllium hydroxide complexes, acts as a phosphate analog, similar to AlF-4 and vanadate.

Aluminum↗
PubMed1986

The relationships among alcohol availability, alcohol consumption and alcohol-related damage in the Province of Ontario and the State of Michigan 1955-1982.

This study examines the relationships among the relative price of alcohol, per capita alcohol consumption and liver cirrhosis mortality rates over a 28 year period in Ontario and Michigan. A high, positive association between per capita consumption and liver cirrhosis mortality was observed for both jurisdictions. In both areas, changes in the relative price of alcohol were inversely related to changes in consumption and cirrhosis mortality. Although causal inferences from these data must be made with caution, the results are strong enough to suggest that policy initiatives concerning the economic availability of alcohol should consider public health consequences.

Alcohol Drinking↗
PubMed1986

Identification and classification of carcinogens: procedures of the Chemical Substances Threshold Limit Value Committee, ACGIH. American Conference of Governmental Industrial Hygienists.

The Chemical Substances Threshold Limit Value Committee of the American Conference of Governmental Industrial Hygienists has refined its procedures for evaluating carcinogens. Types of epidemiologic and toxicologic evidence used are reviewed and a discussion is presented on how the Committee evaluates data on carcinogenicity. Although it has not been conclusively determined whether biological thresholds exist for all types of carcinogens, the Committee will continue to develop guidelines for permissible exposures to carcinogens. The Committee will continue to use the safety factor approach to setting Threshold Limit Values for carcinogens, despite its shortcomings. A compilation has been developed for lists of substances considered to be carcinogenic by several scientific groups. The Committee will use this information to help to identify and classify carcinogens for its evaluation.

Carcinogens↗
PubMed1986

MRI of joint fluid in the normal and ischemic hip.

MR images in 36 hips with documented avascular necrosis and 80 hips without evidence of joint disease were studied to determine the amount and appearance of fluid in the joint. All MRI examinations were done on a 1.5-T machine and included coronal images made with relative T2 weighting (repetition times = 2000-2500 msec, echo delays = 60-100 msec). The amount of joint fluid, which had an intense signal higher than fat, was graded from 0 to 3 and analyzed with respect to the patient's age and radiographic stage of avascular necrosis. Joint fluid was seen in 84% of presumed normal hips. Only four (5%) of 80 had enough fluid to surround the femoral neck (grade 2), and none had sufficient fluid to distend the joint capsule (grade 3). In comparison, 21 (58%) of 36 hips with avascular necrosis had grade-2 or grade-3 effusions (p less than 0.005), and some fluid was seen in all. Grade-3 effusions were seen in seven (50%) of 14 hips with flattening of the femoral head, compared with only one (5%) of 20 in which the femoral contour was normal. It is concluded that small amounts of fluid are present in both normal hips and those with avascular necrosis. In avascular necrosis, increased joint fluid may be present before radiographic abnormalities occur, but it is greatest after there is flattening of the femoral head. MRI is a highly sensitive method for detecting fluid in the hip joint.

Adolescent↗
PubMed1984

Evidence that glycocalicin circulates in normal plasma.

By using a combination of a heterologous antiserum to GPIb/glycocalicin and a radiolabeled monoclonal antibody to GPIb/glycocalicin, we were able to develop a sensitive and specific radioimmunoelectrophoretic assay that can distinguish small amounts of glycocalicin from GPIb. Normal plasmas were found to contain glycocalicin, even in samples treated with protease inhibitors and centrifuged extensively to remove platelets and platelet fragments. Confirmation that the plasma antigen had a relative molecular weight similar or identical to glycocalicin was obtained from studies employing gel chromatography and affinity chromatography. An immunoradiometric assay was developed to quantify plasma glycocalicin, and normal plasma was found to contain approximately 1-3 micrograms/ml. The plasma of a patient with severe thrombocytopenia due to aplastic anemia had less than 12.5% of the normal level of glycocalicin, whereas two patients with thrombocytopenia due to diseases of increased platelet destruction (idiopathic thrombocytopenic purpura and hemolytic-uremic syndrome) had normal levels. Thus, there appears to be ongoing catabolism of platelet GPIb in vivo, and we postulate that the plasma level of glycocalicin reflects a complex function of factors, including platelet count, platelet turnover, and the site of platelet destruction.

Blood Specimen Collection↗