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Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 163 records · Page 9Linked to original sources
PubMed1988

Late reversibility of tomographic myocardial thallium-201 defects: an accurate marker of myocardial viability.

Twenty-one patients were studied who underwent thallium-201 stress-redistribution single photon emission computed tomography (SPECT) both before and after coronary artery bypass grafting (n = 15) or transluminal coronary angioplasty (n = 6). All patients underwent thallium imaging 15 min, 4 h and late (18 to 72 h) after stress as part of the preintervention thallium-201 scintigram. In a total of 201 tomographic myocardial segments with definite post-stress thallium-201 perfusion defects in which the relevant coronary arteries were subsequently successfully reperfused, the 4 h redistribution images did not predict the postintervention scintigraphic improvement: 67 (85%) of the 79 4 h reversible as well as 88 (72%) of the 122 4 h nonreversible segments improved (p = NS). The 18 to 72 h late redistribution images effectively subcategorized the 4 h nonreversible segments with respect to postintervention scintigraphic improvement: 70 (95%) of the 74 late reversible segments improved after intervention, whereas only 18 (37%) of the 48 late nonreversible segments improved (p less than 0.0001). The frequency of late reversible defects and the frequency of postrevascularization improvement of late nonreversible defects are probably overestimated by this study because of referral biases. The cardiac counts and target to background ratios from late redistribution studies resulted in satisfactory cardiac images for visual interpretation. For optimal assessment of the extent of viable myocardium by thallium-201 scintigraphic studies, late redistribution imaging should be performed when nonreversible defects are observed on 4 h redistribution images.

Aged↗
PubMed1988

Activation of cAMP-dependent protein kinase is required for heterologous desensitization of adenylyl cyclase in S49 wild-type lymphoma cells.

We report here that, contrary to previously reported findings, treatment of S49 wild-type (WT) lymphoma cells with 0-50 nM epinephrine resulted in a heterologous desensitization of adenylyl cyclase (EC 4.6.1.1)--that is, epinephrine and prostaglandin E1 (PGE1) stimulations of adenylyl cyclase were reduced. Observation of this heterologous desensitization required the assay of adenylyl cyclase with submillimolar concentrations of Mg2+ and low concentrations of epinephrine. Also, whereas previously there had been no evidence for any role of cAMP-dependent protein kinase in the desensitization of the WT beta-adrenergic receptor, our data comparing the characteristics of the desensitization in WT, kin-, and cyc- lymphoma cells [where kin- and cyc- refer to variants of S49 WT cells lacking cAMP-dependent protein kinase activity (kin-) and the alpha subunit of the stimulatory guanine nucleotide-binding regulatory protein (cyc-)] now suggest that cAMP-dependent protein kinase mediates the heterologous desensitization of adenylyl cyclase. Specifically, we found that only the WT cells exhibited epinephrine-induced heterologous desensitization. The kin- and cyc- cells exhibited only homologous desensitization, and much higher concentrations of epinephrine were required to elicit the homologous desensitization in the variants relative to the heterologous desensitization of the WT. Treatment of WT and cyc- cells with dibutyryl cAMP or treatment of WT with forskolin or PGE1 caused the heterologous desensitization of adenylyl cyclase, indicating that neither receptor occupancy nor activation of adenylyl cyclase was necessary for the heterologous desensitization.

Adenylyl Cyclases↗
PubMed1988

Patient motion in thallium-201 myocardial SPECT imaging. An easily identified frequent source of artifactual defect.

Because Tl-201 SPECT requires that patients remain in an awkward position for a prolonged time, patient motion is a potentially serious source of artifactual defects on tomographic reconstructions. Thus, a simple method was developed for detection and correction of motion from SPECT images using a Co-57 point source placed on the lower anterior chest, an area remaining in the camera's field of view throughout imaging. In the absence of motion, this point source inscribes a straight line on planar summation of the 32 projections over 180 degrees. Movement is detected by deviation from this line. The number of pixels of motion is used to shift images so that the resultant images of the point source are linear. The method of motion detection and correction was tested in 48 consecutive patients undergoing Tl-201 SPECT. The corrected and uncorrected images were reconstructed and long and short axis tomographic cuts were quantitatively analyzed using circumferential profiles of maximal counts with comparison to the lower limits of normal. Motion was detected in eight of 48 patients (17%). The amount of motion was 2 pixels in three patients and 1 pixel in five patients. Quantitative defect extent was less after correction in seven of eight patients, with a mean decrease of 71% in patients with 2 pixel motion and 44% in patients with 1 pixel motion. This corresponded with a definite reduction in the size of the tomographic defect by visual analysis, and closer resemblance to quantitatively analyzed planar images performed either before or after tomography in the same patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Modulation of carcinoembryonic antigen release by HT-29 colon carcinoma line in the presence of different agents.

In this study we followed the effects of various differentiating agents on the expression of carcinoembryonic antigen (CEA) released into the medium by a colon carcinoma cell line HT-29. Butyric acid 1 mM markedly increased the level of CEA (12-fold in comparison to control levels). 12-O-tetradecanoyl-phorbol-13-acetate (TPA) 50 ng/ml and 5-azacytidine 4 x 10(-6) M increased the amount of CEA, 2- and 1.5-fold respectively. On the other hand retinoic acid 10(-5) M, N methyl-formamide 1% and N,N hexamethylene bisacetamide 2.5 mM decreased CEA 2-, 4- and 3-fold respectively. Our results emphasize that various differentiating agents affect CEA levels differently. Thus changes in CEA levels appear not to be reliable as a marker of a more differentiated phenotype.

Acetamides↗
PubMed1987

Efficacy of recainam, a new antiarrhythmic drug, for control of ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral recainam hydrochloride, a newly synthesized compound, were assessed during a 2-part study of 12 patients with frequent (at least 30/hour) ventricular premature complexes (VPCs). During the initial dose-ranging phase, 11 patients with qualifying arrhythmias (median VPC frequency 575/hour, range 37 to 1,494) received incremental oral doses of 100, 300 and 500 mg of recainam given every 8 hours, each for 3 days. Efficacy was assessed on the last day of each dose. The 300-mg/day dose of recainam was generally ineffective; the 900-mg/day dose was partially effective (58% median VPC reduction, p = 0.03); and the 1,500-mg/day dose was very effective (79% reduction, p less than 0.003). Median reductions in repetitive beats (beats in couplets and runs) for the 3 doses were 18% (difference not significant), 94% (p less than 0.01), and 98% (p less than 0.004), respectively. Recainam provided individual efficacy (at least 70% VPCs or at least 90% repetitive beat suppression, or both) in 7 (64%) of the patients taking 900 mg/day and in 8 (73%) taking 1,500 mg/day. Minimum steady-state plasma concentrations were higher in responders (1.8 +/- 0.5 microgram/ml) than in nonresponders (1.0 +/- 0.5 microgram/ml) (p less than 0.05). The electrocardiographic response to recainam (1,500 mg/day) included increases in PR (by 22%, p less than 0.003) and QRS (by 14%, p less than 0.002) intervals and a small decrease in JTc duration (by 9%, p less than 0.04). Radionuclide ejection fraction did not change. Noncardiac adverse reactions were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Kinetic, structural, and spectroscopic identification of geminate states of myoglobin: a ligand binding site on the reaction pathway.

Elementary steps or geminate states in the reaction of gaseous ligands with transport proteins delineate the trajectory of the ligand and its rebinding to the heme. By use of kinetic studies of the 765-nm optical "conformation" band, three geminate states were identified for temperatures less than approximately 100 K. MbCO, which is accumulated by photolysis between 1.2 and approximately 10 K, was characterized by our previous optical and X-ray absorption studies [Chance, B., Fischetti, R., & Powers, L. (1983) Biochemistry 22, 3820-3829]. Between 10 and approximately 100 K, geminate states that are also identified that have recombination rates of approximately 10(3) s-1 and approximately 10(-5) s-1 (40 K). Thus, it is possible to maintain a steady-state nearly homogeneous population of the slowest recombining geminate state, Mb, by regulated continuous illumination (optical pumping). Both X-ray absorption and resonance Raman studies under similar conditions of optical pumping show that the heme structure around the iron in Mb is similar to that of MbCO. In both geminate states, the iron-proximal histidine distance remains unchanged (+/- 0.02 A) from that of MbCO while the iron to pyrrole nitrogen average distance has not fully relaxed to that of the deoxy state. In MbCO the CO remains close to iron but not bound, and the Fe...CO angle, which is bent in MbCO (127 +/- 4 degrees C), is decreased by approximately 15 degrees [Powers, L., Sessler, J. L., Woolery, G. L., & Chance, B. (1984) Biochemistry 23, 5519-5523]. The CO molecule in Mb, however, has moved approximately 0.7 A further from iron. Computer graphics modeling of the crystal structure of MbCO places the CO in a crevice in the heme pocket that is just large enough for the CO molecule end-on. Above approximately 100 K resonance Raman studies show that this structure relaxes to the deoxy state.

Binding Sites↗
PubMed1987

An analysis of 248 initial mobilization tests performed on an ambulatory basis.

Data are presented on 248 initial mobilization tests performed in an ambulatory setting over an 11-year period. Results demonstrate that there is no single, consistent predictor of body burden of lead, although the higher the blood lead level, the greater the amount of excretable (mobilizable) lead. It is recommended that an appropriate ratio of lead excreted in response to chelant is equal to or greater than 0.5 based on this series of tests. A recommendation is also made to realign the Centers for Disease Control (Atlanta) guidelines for classification of risk. This realignment would coincide with a recommendation that mobilization tests be reserved for children whose blood lead levels ranged from 1.93 to 2.57 mumol/L (40 to 60 micrograms/dL). Those with higher levels would undergo chelation without prior mobilization studies.

Ambulatory Care↗
PubMed1987

The detection of brain antigens within the circulating immune complexes of patients with multiple sclerosis.

Immune complexes isolated from sera of patients with multiple sclerosis (MS) were analyzed for their antigenic content. Immune complexes precipitated with polyethylene glycol were inoculated into rabbits. The antisera raised were shown to react to MS and normal brain antigens by crossed immunoelectrophoresis, ELISA and nitrocellulose transfer. Additionally, these antisera reacted by co-precipitation with the measles nucleocapsid antigen. As persistent viral infection has not been shown to occur in MS, these studies support the possibility that brain antigens within the immune complex share antigenic determinants with a specific viral antigen seen earlier in life by the host.

Animals↗
PubMed1987

Beta-adrenergic receptor desensitization of wild-type but not cyc lymphoma cells unmasked by submillimolar Mg2+.

Treatment with low physiological concentrations of epinephrine (5-50 nM) rapidly desensitizes beta-adrenergic stimulation of cAMP formation in S49 wild-type (WT) lymphoma cells. Previous attempts to detect this early phase of desensitization in cell-free assays of adenylate cyclase (EC 4.6.1.1) after intact cell treatment were unsuccessful. We have now found that reducing the Mg2+ concentrations in the adenylate cyclase assays to less than 1.0 mM unmasked this rapid phase of desensitization of the WT cells, and that high Mg2+ concentrations (5-10 mM) largely obscured the desensitization. Submillimolar Mg2+ conditions also revealed a two- to threefold decrease in the affinity of epinephrine binding to the beta-adrenergic receptor after desensitization with 20 nM epinephrine. Detection of 4 beta-phorbol 12-myristate 13-acetate (PMA) desensitization of the WT beta-adrenergic receptor was also dependent on low Mg2+ as measured either by the decrease in epinephrine stimulation of adenylate cyclase or by the reduction in the affinity of epinephrine binding. Unexpectedly, when cyc- cells were pretreated with 50 nM epinephrine, the beta-adrenergic stimulation of reconstituted adenylate cyclase was not desensitized. The characteristics of the Mg2+ effect on epinephrine- and PMA-induced desensitizations suggest a similar mechanism of action with the most likely events being phosphorylations of the beta-adrenergic receptors. Our data indicate that cAMP-dependent protein kinase (EC 2.7.1.37) may play a role in the desensitization caused by low epinephrine concentrations inasmuch as this phase of desensitization did not occur in the cyc-. For the PMA-induced desensitization, the phosphorylation may be mediated by protein kinase C (EC 2.7.1.37).

Adenylyl Cyclases↗
PubMed1987

Basic fibroblast growth factor: production and growth stimulation in cultured adrenal cortex cells.

Cultured bovine adrenal cortex cells express the basic fibroblast growth factor (bFGF) gene and contain, but under normal conditions apparently do not release, bFGF. However, once released, bFGF can stimulate proliferation of the cells, indicating that it could act as a self-stimulating growth factor for adrenal cortex cells. It is conceivable that the intracellular bFGF is released upon injury of the adrenal cortex and that it may be involved in the subsequent tissue repair mechanisms by stimulating the proliferation of adrenal cortical and vascular endothelial cells.

Adrenal Cortex↗
PubMed1986

Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor.

Basic and acidic fibroblast growth factors (FGF's) are potent mitogens for capillary endothelial cells in vitro, stimulate angiogenesis in vivo, and may participate in tissue repair. An oligonucleotide probe for bovine basic FGF was designed from the nucleotide sequence of the amino-terminal exon of bovine acidic FGF, taking into account the 55 percent amino acid sequence homology between the two factors. With this oligonucleotide probe, a full length complementary DNA for basic FGF was isolated from bovine pituitary. Basic FGF in bovine hypothalamus was shown to be encoded by a single 5.0-kilobase messenger RNA; in a human hepatoma cell line, both 4.6- and 2.2-kilobase basic FGF messenger RNA's were present. Both growth factors seem to be synthesized with short amino-terminal extensions that are not found on the isolated forms for which the amino acid sequences have been determined. Neither basic nor acidic FGF has a classic signal peptide.

Angiogenesis Inducing Agents↗
PubMed1986

Homologous desensitization of beta-adrenergic receptors in lymphoma cells is not altered by the inactivation of Ni (Gi), the inhibitory guanine nucleotide regulatory protein.

We had previously demonstrated that the cyc- mutant of S49 wild-type lymphoma cells both desensitizes and undergoes a sequestration-internalization of the beta-receptor in response to short-term treatment with adrenaline. The cyc- mutant of S49 wild-type lymphoma cells lacks the alpha s subunit of the stimulatory coupling protein Ns, but has fully functional Ni, the inhibitory component of the regulatory complex. This suggested that functional Ns was not required for desensitization. To examine the role of Ni in desensitization, both S49 wild-type and cyc- cells were treated with islet-activating protein under conditions that led to over 85% attenuation of Ni function in S49 wild-type cells and approx. 50% attenuation of Ni function in cyc- cells. This treatment had no effect on the adrenaline-induced desensitization of adenylate cyclase or the sequestration event measured by the apparent movement of beta-adrenergic receptors to a light-vesicle fraction. Further, the desensitization event, which occurs before the sequestration event, observable only in intact cells, was also not altered by islet-activating-protein pretreatment of S49 wild-type cells. The data suggest that a functional Ni is not required for desensitization in the S49 lymphoma cells.

Adenosine Diphosphate↗
PubMed1986

Human basic fibroblast growth factor: nucleotide sequence and genomic organization.

Clones encoding the angiogenic endothelial cell mitogen, basic fibroblast growth factor (FGF), have been isolated from human cDNA libraries made from kidney, fetal heart, fetal liver, term placenta, and a breast carcinoma. Basic FGF cDNA clones are present in these libraries at very low levels when compared to the quantity of the growth factor in the tissues. This observation, combined with the fact that several of the clones represent unspliced transcripts, suggests that cytoplasmic basic FGF mRNA is unstable and that the protein is stored in tissues. The amino acid sequence of human basic FGF, deduced from the sequence of these cDNAs and from genomic clones, is 99% homologous to that of bovine basic FGF, implying a strong selection pressure for maintenance of function and structure. As with the bovine factor, human basic FGF does not appear to have a signal peptide sequence. Southern blot analysis of human genomic DNA and mapping of the cloned gene shows that there is only one basic FGF gene. All of the basic, heparin-binding endothelial cell mitogens of similar amino acid composition that have been described must therefore be products of this single gene.

Amino Acid Sequence↗
PubMed1986

Different inducibility and possible significance of several concomitant "fragile sites" in two brothers.

Concomitance of four fragile sites (at 16p13, 16q22, 16q23, Yq12) in the lymphocyte cultures of two brothers is reported. The expression of each of these fragile sites was enhanced (or induced) by different culture conditions. Some of the inducing conditions are already known and others are reported here for the first time. The meaning of the fragile sites is discussed and a possible viral etiology suggested. Concomitance of some of them may be a potential causal factor for deletions, translocations, or inversions.

Chromosome Fragile Sites↗