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S Feinstein

Publications and source records attributed to S Feinstein.

36 records · Page 2Linked to original sources

Purification and properties of the alpha-interferon receptor of human lymphoblastoid (Namalva) cells.

The interferon receptor was solubilized from human lymphoblastoid (Namalva) cell membranes with Triton X-100. It was purified by chromatography on wheat-germ lectin-Sepharose and hydroxyapatite and by affinity chromatography on interferon-hexanoyl-Sepharose. The partially purified receptor was analyzed by gel filtration on Sepharose 6B and by sucrose gradient sedimentation in the presence of 0.1% Triton X-100. Gel filtration analysis yielded a Stokes radius of 74 A for the receptor-Triton X-100 complex. Sedimentation in sucrose gradients revealed an heterogeneous pattern of distribution with a plateau of activity between 4 and 10 S. Removal of suspected lipid material and Triton X-100 by extraction with isoamyl alcohol resulted in an accelerated rate of receptor sedimentation in a sodium dodecyl sulfate-containing sucrose gradient. Under these conditions it manifested an apparent sedimentation coefficient of 13.6 S. The dissociation constants Kd derived from Scatchard analysis of binding data with the purified receptor were in the range of 0.2-0.5 nM.

Cell Line↗

Hearing loss following Hemophilus influenzae meningitis in infancy. Diagnosis by evoked response audiometry.

Bacterial meningitis is a major cause of sensorineural hearing loss during childhood. This study compared the efficacy of auditory brain-stem evoked response (ABER) testing with conventional conditioned orienting response (COR) testing in the early diagnosis of postmeningitic deafness in 34 infants younger than 2 years of age, with a diagnosis of Hemophilus influenzae meningitis. In most of the children (62%), results of the two tests were in agreement. The use of ABER testing appeared to be more effective than COR audiometry for the testing of infants younger than 6 months of age, for older children with perceptual handicaps, and for the identification of small children with unilateral hearing loss.

Audiometry↗

Prospective evaluation of the risk of upper gastrointestinal bleeding after admission to a medical intensive care unit.

One hundred seventy-four patients (179 admissions) were prospectively evaluated for the subsequent occurrence of upper gastrointestinal ("stress") bleeding after admission to a medical/respiratory intensive care unit. Evidence for either overt or occult gastrointestinal bleeding developed in 25 (14 percent). The group of bleeders had a higher mortality (64 percent versus 9 percent), duration of intensive care unit stay (median 14.2 versus 4.2 days), number of patients requiring mechanical ventilatory support (84 percent versus 26 percent), and duration of such support for those who required it (median 9.5 versus 4.2 days) than the group who did not bleed. In three patients, death was related to bleeding. Upon patients' admission to the intensive care unit, diagnoses of an acute respiratory illness (but not specifically chronic obstructive pulmonary disease), a malignancy, or sepsis were more common among those who subsequently bled. Of factors tested, a coagulopathy and the need for mechanical ventilation were most strongly associated with the risk of bleeding. Other factors did not add to the risk once these two were taken into account. Among patients receiving mechanical ventilation, the risk of overt bleeding was particularly low for those who required such support for less than five days (only 3 percent). It is concluded that (1) significant upper gastrointestinal bleeding occurring after medical intensive care unit admission is an uncommon event, and (2) prolonged mechanical ventilation and/or the presence of a coagulopathy are the most potent risk factors. Medical patients with either of the latter conditions are most likely to benefit from prophylaxis regimens against "stress"-induced upper gastrointestinal bleeding.

Adult↗

Computer methods for myocardial contrast two-dimensional echocardiography.

Two computer-aided videodensitometric methods that may be used in conjunction with two-dimensional contrast echocardiography were examined to quantify the time course of echographic opacification in the myocardium after experimental injections of contrast agents (hand-agitated Renografin-saline and sonicated sorbitol 70% solutions) into the left main coronary artery. Echographic studies of myocardial cross sections were digitized with an image processing computer using a 128 X 128 resolution matrix. Both stop frame and continuous cycle modes of acquisition were performed. A set of computer programs was developed to extract and analyze time-intensity curves from the digitized images. These included cardiac outline delineation, segmental division, regional intensity computation and exponential curve analysis. The stop frame method was applied to experimental studies in 17 closed chest dogs during control states and after coronary occlusions. Significant differences were found in the decay half-lives of echo intensity between normal (24 +/- 8 seconds) and acutely ischemic (293 +/- 165 seconds; p less than 0.001) myocardium for the Renografin-saline solution. Interobserver reproducibility of the measured half-lives was r = 0.91 and standard error of the estimate = 5 seconds. The continuous cycle method of analysis was examined in five closed chest dogs (with up to six injections per dog), applying the sonicated sorbitol 70% solution in only the control state. The mean half-life was 4.2 +/- 1.1 seconds. These computer-based videodensitometric methods might be applied to a wide variety of experimental studies in two-dimensional contrast echocardiography that attempt to quantify myocardial perfusion and function.

Animals↗

Myocardial contrast two-dimensional echocardiography: experimental examination at different coronary flow levels.

Regional myocardial echo contrast appearance-disappearance after intracoronary contrast agent injection was examined with computerized two-dimensional contrast echocardiography in eight open chest dogs during successive variation of the coronary blood supply. A new sonication method applied to dextrose 50% produced an echo contrast agent with a microbubble size of 12 +/- 6 mu (mean +/- standard deviation), and 1 cc of this agent was injected into a coronary artery during the echocardiographic study of the left ventricle. Left anterior descending or circumflex coronary artery flow, measured by electromagnetic flowmeter, was successively reduced up to 90% with an extravascular hydraulic occluder, or else increased 40 to 60% through intravenous dipyridamole infusion (7 to 10 micrograms/kg per min). The corresponding myocardial echo time-intensity curves were analyzed for each of 12 segments of a midventricular short-axis cross section. Several potential indexes of myocardial perfusion were derived: peak echo contrast intensity, time from echo contrast appearance to peak intensity, half-life of echo contrast decay phase (T 1/2) and total duration of contrast appearance-disappearance. Except for peak intensity, all of these indexes provided significant (p less than 0.05) differentiation between control coronary flow (66 +/- 17 ml/min) and greater than 50% flow reductions (26 +/- 6 ml/min) or hyperemia (115 +/- 17 ml/min). Half-life values were 5.2 +/- 0.3 seconds for the control state, 9 +/- 2 seconds for the reduced coronary flow and 2 +/- 2 seconds for dipyridamole hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Physical factors influencing quantitation of two-dimensional contrast echo amplitudes.

Measurement errors that may interfere with quantitation by the new myocardial contrast two-dimensional echocardiographic technique were examined in a simplified in vitro model consisting of a 50 cc blood-filled balloon with supplemental controlled injection of 0.2 to 2.6 cc of sonicated dextrose 70%. The blood-contrast mixture in the balloon volume was imaged with two-dimensional echocardiography and discrete regions were studied for both magnitude and time course of echo intensities. Preliminary evidence indicates that a regional contrast echo intensity measurement is significantly modified by contrast-related ultrasound attenuation in intervening regions and by the amount and mode of contrast material injection. Thus, injection of 1.2 cc contrast material resulted in substantially higher peak echo intensity and a more rapid decay than injection of 0.8 or 0.6 cc. These measurements were also found to be influenced by the echographic system signal processing and time-gain compensation which contribute to nonlinear and unevenly compensated image distribution of echo amplitudes. Other factors are discussed, including transducer-related image resolution and image texture, contrast agent bubble size and persistence and computer methods for standardized selection of region of interest and analysis of the regional contrast intensity decay curve.

Blood↗

Two-dimensional contrast echocardiography. II. Transpulmonary studies.

A method using contrast two-dimensional echocardiography for left ventricular chamber and myocardial opacification from a right-sided pulmonary capillary wedge position is described. A total of 152 studies were carried out in nine mongrel dogs. Four different catheters with different catheter tip cross-sectional areas (varying from 0.75 to 2.3 mm2) were used. In addition, catheter position (six different positions in the pulmonary circulation), pressure of injection and type of echo contrast agent (hand-agitated and sonicated) were studied. In all 152 studies, two independent observers agreed that echo contrast was seen in the left ventricular chamber after a pulmonary capillary wedge injection of 8 cc of echo contrast agent followed by a flush injection of 8 cc saline solution. In 71% of the studies, the two independent observers agreed about the degree of opacification on a qualitative scale of 0 to 3+. Time from injection from the catheter tip to the appearance of echo contrast in the left atrium was 6.2 +/- 4.8 seconds for sonicated Renografin-76 and 2.8 +/- 0.6 seconds for sonicated sorbitol 70% (p less than 0.05). Correlation for the disappearance rate of echo contrast as determined for the region in the mid left ventricular chamber and thermodilution cardiac output was fair (r = -0.78; n = 14). In 24 studies, it was not possible to demonstrate the appearance of echo contrast in the myocardium. Peak videointensity of 10 duplicate injections showed a mean percent error of 10.4 +/- 2.1% for sonicated Renografin-76 and 1.4 +/- 0.8% for sonicated sorbitol 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Submitral atheromatous lesions in monkey and man.

Posterior submitral recess (PSMR) calcification is a common autopsy finding in elderly people, but its pathogenesis is undetermined. In this communication we show that, in part at least, the PSMR changes at autopsy are atheroma-like with lipid around the sclerosis and calcific deposits. These changes in the PSMR showed a statistically significant correlation with the presence of hypertension and with an autopsy finding of severe coronary atherosclerosis. We showed, for the first time, that similar fibrosis and lipid deposition in the PSMR can be produced in high-fat, high-cholesterol fed macaque monkeys (Macaca arctoides) with or without concomitant experimentally produced hypertension. It is concluded that changes in the PSMR in monkeys and man are strongly related to atherosclerosis and hypertension.

Adult↗

Pulmonary and hemodynamic function in dogs during exercise: effects of lung autotransplantation.

An airtight facemask/mouthpiece assembly has been devised to facilitate the performance of a wide range of pulmonary function tests during treadmill exercise in dogs. Using this appliance, data were obtained from 6 normal dogs and 3 of the same dogs after left lung autotransplantation. All measurements were made during awake, resting conditions and again after 5-7 minutes of moderate exercise. Resting values for pulmonary function tests, hemodynamic parameters, blood gases and pH from both pulmonary and systemic arterial blood samples did not differ significantly between normal dogs and those studied after left lung autotransplantation. During treadmill exercise, cardiac output doubled and pulmonary vascular resistance decreased comparably in both groups of dogs. Heart rates in both groups rose to approximately 22 b/min and blood gases and pH remained normal. These results indicate the facemask/mouthpiece assembly permits normal ventilation during treadmill exercise. In addition, these data support the view that pulmonary autotransplantation per se need not impose obligatory defects in ventilatory and hemodynamic function despite the increased demands of treadmill exercise.

Animals↗

Human lymphoblastoid interferon for clinical trials: large scale purification and safety tests.

Human lymphoblastoid cell lines are one of the best sources for the production of large amounts of human interferon for clinical trials. The potential risk of using transformed cell lines for production of a substance for human use can be overcome by an extensive purification of the interferon to a high degree, and by carefully testing the final product for DNA content and toxic materials. In previous reports we described a method for large scale production of interferon by a human lymphoblastoid cell line (Namalva). In this report a system for large scale purification of Namalva interferon and safety tests is presented. The procedure consists of three main steps: 1. Concentration of crude interferon by ultrafiltration. II. Gel filtration on Sephadex G-75 or Ultrogel AcA 54 columns. III. Affinity chromatography on anti-interferon antibody column. All steps were adapted for the processing of batches of hundreds of litres and can be easily further scaled-up. The final highly purified product undergoes a series of quality control tests such as purity, sterility, toxicity, pyrogenicity and DNA content. After passing all tests the IFN is released for clinical trials.

Cell Line↗

Isolation of two species of human lymphoblastoid (Namalva) cell-derived interferon that differ in rates of clearance, size, and cell specificity.

Chromatography of human lymphoblastoid (Namalva) interferon on blue dextran Sepharose has separated the interferon activity into two species which differ in affinity to the dye Cibacron Blue F3GA. The separated species differ also in rates of clearance from the circulation of mice, size, and specificity toward human and bovine cells. The species retained by the dye manifests a slower clearance rate, is about 20,000 mol. wt., and is equally active on both human fibroblasts FS-11A and bovine cell line MDBK. The unretained species disappears from the circulation at a faster rate, is 16,000 mol. wt., is active on bovine cells, but almost inactive on human cells. It is suggested that a comparative study of the two species may aid in the elucidation of the causes responsible for the rapid clearance or bioinactivation of interferon.

Animals↗

Factors affecting the large scale production of human lymphoblastoid interferon.

Large scale production of human lymphoblastoid (Namalva) interferon (IFN) is carried out in pilot-plant-scale fermentors having up to 250 liter culture volume. Cells are grown in a semi-continuous culture. For IFN production, which is an IFN-alpha (Ly), harvested cells were induced by Sendai virus. Variations in IFN yields of up to ten-fold were observed during long-term cell cultivation. Several factors such as cell concentration, virus concentration, "age" of induced cells and serum substitutions, were investigated for their effect on the fluctuation in the IFN yields. Optimization of the above factors were found to be of great importance in controlling the IFN production and maintaining a stable and high IFN yield.

Cell Division↗

Usher's syndrome type III.

We describe a rare example of Usher's syndrome type III in a 9-year-old boy. This type is characterized by retinitis pigmentosa and progressive sensorineural deafness.

Audiometry↗

Coacervate microspheres as carriers of recombinant adenoviruses.

The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by difficulties in directing the viruses to specific sites and by the requirement for bolus administration, both of which limit the efficiency of target tissue infection. As a first step toward overcoming these limitations, rAds were encapsulated in coacervate microspheres comprised of gelatin and alginate followed by stabilization with calcium ions. Ultrastructural evaluation showed that the microspheres formed in this manner were 0.8-10 microM in diameter, with viruses evenly distributed. The microspheres achieved a sustained release of adenovirus with a nominal loss of bioactivity. The pattern of release and the total amount of virus released was modified by changes in microsphere formulation. Administration of the adenovirus-containing microspheres to human tumor nodules engrafted in mice showed that the viral transgene was transferred to the tumor cells. It is concluded that coacervate microspheres can be used to encapsulate bioactive rAd and release it in a time-dependent manner.

Adenoviridae↗

Mutagenicity studies with 5-thio-D-glucose. Cytogenetic investigation in mice, and the sex-linked recessive lethal gene test in Drosophila.

Cytogenetic studies in bone marrow cells and dividing spermatocytes I in male mice and the sex-linked recessive lethal gene test in Drosophila melanogaster were initiated to evaluate the mutagenic potential of 5-thio-D-glucose, a reversible male contraceptive in some mammals. The compound was administered by oral intubation to mice at 40 or 60 mg/kg for various time periods. Oregon-R D. melanogaster males were fed medium containing 600 or 1200 ppm of the substance for 72 hours and mated with virgin Muller-5 females to test for gene mutation. The compound did not enhance structural and numerical chromosomal aberrations or elevate sex-linked recessive lethals in D. melanogaster. It is concluded that under the conditions of the present study 5-thio is a nonmutagenic male antifertility agent.

Animals↗