Comment on "Quantum mechanics, local realistic theories, and Lorentz-invariant realistic theories"
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Journal Article↗
Biomedical subjects
S Goldstein
Publications and source records attributed to S Goldstein.
Angiographic evidence of right coronary bridging.
Systolic constriction of the left anterior descending coronary artery is a well-recognized angiographic and autopsy finding. The etiology of this phenomenon is an intramural course of the coronary artery. Even though there has been autopsy evidence of an intramural course of the right coronary artery, this rare finding has not been associated with systolic constriction, "bridging" on coronary angiography. There is evidence that strenuous exercise can induce ischemia in an intramural left coronary artery. We therefore present a case report of angiographic evidence of systolic constriction of the right coronary artery.
Aged↗
Senescence and cell density of human diploid fibroblasts influence metabolism of insulin-like growth factor binding proteins.
In order to analyze changes in metabolism of insulin-like growth factor binding proteins (IGFBPs) related to cell senescence and cell density, we compared human diploid fibroblasts (HDF) in the proliferatively vigorous first half (young cells) and senescent HDF in the last 10% (old cells) of the replicative lifespan after seeding cells over an eightfold range and proliferation to high density. Increasing the seeding cell density of both young and old HDF led to elevated rates of IGFBP-3 secretion, an increasing ratio of the 42/38 kDa species of IGFBP-3, and degradation of all species of IGFBPs derived from both the fetal bovine serum component of the culture medium and from HDF. At a given seeding density old HDF produced more IGFBP-3 and degraded more IGFBPs than young HDF. IGFBP-4 was degraded by a protease that appeared to be different from the protease(s) involved in degradation of the other IGFBPs. Young HDF at all seeding densities contained a cell-associated 29 kDa IGFBP, whereas this protein could not be detected in old cells. Thus, although certain changes in IGFBP metabolism are similar in young HDF seeded at high densities and in old HDF, young and old phenotypes can be distinguished by characteristic qualitative and quantitative changes in IGFBPs derived from fetal bovine serum and from HDF.
Blotting, Western↗
Overexpression of plasminogen activator inhibitor type-1 in senescent fibroblasts from normal subjects and those with Werner syndrome.
We previously reported that plasminogen activator inhibitor type-1 (PAI-1) mRNA was present at higher steady-state levels in prematurely senescent fibroblasts derived from a subject with Werner syndrome (WS) compared to early passage (EP) fibroblasts from an age-matched normal subject (Murano et al., 1991, Mol. Cell. Biol. 11:3905-3914). To explore the generally of this phenomenon with respect to chronological age of donor (in vivo aging) and the late-passage (LP) or senescent phase of the fibroblast replicative lifespan, we assayed PAI-1 mRNA in cells and PAI-1 antigen in medium conditioned by 20 normal fibroblast strains at EP and LP and six WS strains during their curtailed replicative lifespans. The lowest accumulations of PAI-1 were found in medium conditioned by fetal and newborn cells with a shallow but progressive rise seen in postnatal cells from normal donors of increasing chronological age. With few exceptions, normal LP fibroblasts showed increased PAI-1 accumulations in medium compared to their EP counterparts. Conditioned medium from four of the six WS strains showed PAI-1 accumulations that were significantly higher than the media of any normal controls at EP and LP. PAI-1 mRNa levels were generally commensurate with the cumulative amount of PAI-1 in the medium but the frequent exceptions indicate that translational and post-translational mechanisms also regulate PAI-1 output. The augmentation in PAI-1 output of fibroblasts as a direct function of chronological age and during in vitro senescence suggests that PAI-1 may play an important role in the reduced capacity for wound healing and the increasing tendency to thrombogenesis and atherogenesis seen during biological aging and in particular in persons with Werner syndrome.
Adult↗
Altered regulation of fibronectin gene expression in Werner syndrome fibroblasts.
Fibronectin (FN) production was quantified in the extracellular medium and in extracts of human diploid fibroblasts (HDF) by enzyme-linked immunosorbent assay and by immunoprecipitation of [35S]methionine biosynthetically labeled proteins. FN output was increased in normal late passage (old) HDF and in prematurely senescent Werner syndrome (WS) fibroblasts, compared to normal early passage (young) HDF. Output was maximal when cells were preconfluent, exceeding the level found at confluence and postconfluence. For all cell types the highest proportion of newly synthesized FN was found in the extracellular compartment. Both young and old HDF exposed to regular growth medium containing 15% fetal bovine serum (FBS) secreted twice as much FN as when exposed to serum-free medium, and cognate mRNA levels were commensurate with protein output. WS fibroblasts secreted 1.6-fold more FN than old HDF when both cell types were exposed to medium containing 15% FBS. Immunofluorescent analysis revealed greater association of FN with WS and old HDF than with young HDF. Furthermore, WS cells exposed to 15% FBS contained 3.4-fold more FN mRNA and produced seven times more FN protein compared to WS cells exposed to serum-free medium. Thus, WS fibroblasts secrete more FN than old normal and young normal HDF in the presence of 15% FBS due to augmentation of FN mRNA levels and enhanced efficiency of FN mRNA translation and/or post-translational processing.
Animals↗
Divergent effects of intravenous dobutamine and nitroprusside on left atrial contribution to ventricular filling in dogs with chronic heart failure.
The left atrial (LA) contribution to left ventricular (LV) filling is often attenuated in patients with heart failure. It remains uncertain, however, whether therapy with positive inotropic agents or vasodilators improves or further impairs this maladaptation. In the present study, the effects of intravenous dobutamine and nitroprusside on the LA contribution to LV filling was examined in seven dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. Pulsed Doppler echocardiography was used to measure mitral inflow velocity before and after an intravenous infusion of dobutamine (4 micrograms/kg/min) and an intravenous infusion of nitroprusside (3 micrograms/kg/min). The percent LA contribution to LV filling was calculated as the ratio of the time-velocity integral of the LA component of mitral inflow velocity (Ai) to the time-velocity integral of total diastolic inflow velocity (Ti) times 100. Dobutamine increased LV filling pressure, LV end-diastolic wall stress, LV end-diastolic stiffness, and Ei, but had no effect on Ai or the percent LA contribution to filling (14% +/- 3% vs 12% +/- 2%) (p < 0.34). In contrast, nitroprusside decreased LV filling pressure, LV end-diastolic wall stress, and end-diastolic stiffness, and increased Ei, Ai, and the percent LA contribution to LV filling (12% +/- 2% vs 17% +/- 2%) (p < 0.01). The results indicate that dobutamine and nitroprusside have divergent effects on the LA contribution to LV filling. In dogs with chronic heart failure, dobutamine appears to impair LA contribution to the LV filling by augmenting LA workload, whereas nitroprusside appears to elicit greater LA contribution to LV filling by reducing the LA workload.
Animals↗
Escherichia coli heat-stable toxin receptors in human colonic tumors.
BACKGROUND/AIMS: Escherichia coli heat-stable enterotoxins (ST) are small peptides of 18 or 19 amino acids that bind to specific cell surface receptors located on the intestinal brush border and activate guanylate cyclase, resulting in an increase in the intracellular cyclic guanosine 3',5'-monophosphate content of the cell. The present study examined whether receptors for ST are expressed by primary and metastatic human colonic tumors in vivo. METHODS: Plasma membranes prepared from surgical tissue samples from normal colon, liver and lung, primary colonic adenocarcinomas, and colon carcinomas metastatic to lung and liver were analyzed for the structural and functional characteristics of constituent ST receptors. RESULTS: All primary and metastatic colonic tumors examined bound ST, showing receptors of high (pmol/L) and low (nmol/L) affinity with densities that were similar to those in normal colon. Also, affinity cross-linking of labeled ST to membranes showed similar binding proteins in primary and metastatic tumors and normal colon. ST binding and affinity-labeled proteins were not detected in normal extraintestinal tissues. Guanylate cyclase was activated by ST in membranes from all colonic tumors studied, with efficacies and potencies that were similar to those in normal colon. ST did not activate this enzyme in normal extraintestinal tissues. CONCLUSIONS: Receptors for ST are expressed by primary and metastatic human colonic tumors in vivo, with structural and functional characteristics that are similar to those in normal human colon.
Adenocarcinoma↗
Task Force 4: The relationship between cardiovascular specialists and generalists.
1. An imbalance between generalists and cardiovascular subspecialists exists that will require decades to correct. We question the validity of the 50:50 generalist/specialist ratio in view of current practice patterns for cardiology. 2. There has been a large increase in the number of cardiovascular specialists in the past 30 years that will continue if training programs remain at their current size. 3. Cardiovascular specialists provide a substantial amount of inpatient care, care to older patients and care to those with cardiovascular symptoms, although generalists actually provide the majority of office-based cardiovascular care. 4. A significant portion of cardiovascular specialist care can be classified as comprehensive care to patients with and without cardiovascular disease. 5. Most generalists and cardiovascular specialists do not perceive a need for additional cardiovascular specialists. 6. Many providers perform cardiovascular procedures at levels below the recommended threshold for maintenance of clinical competence. 7. Managed care may result in a reduced demand for cardiovascular specialists. 8. If cardiovascular specialists provide general care, it may not be assumed that previous training prepares them for generalist practice. 9. The appropriate boundaries of cardiovascular care between generalists and cardiovascular specialists are indistinct. They are defined somewhat by the training programs from which the generalists graduate. 10. Many generalists have deficiencies in basic skills in clinical cardiology. 11. Desirable interactions between generalists and cardiovascular specialists involve referral of patients in both directions to the provider who can give care to a given patient, at a given time, with the best outcome and lowest cost.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiology↗
Free radicals induced peptide damage in the presence of transition metal ions: a plausible pathway for biological deleterious processes.
When aqueous N2O-saturated solutions containing glycine-N-tert-butylamide (L) and Cr2+ (aq) or Cu+ (aq) are irradiated, transients with metal-carbon sigma-bonds are formed with rate constants of (4.4 +/- 0.5) x 10(7) and (5.2 +/- 0.3) x 10(9) M-1 s-1, respectively. In the chromium(II) system, after a fast process (k = 43 +/- 4 s-1), possibly chelation, the transient decomposes very slowly (k = 0.003 +/- 0.001 h-1) via a beta-elimination process to yield 2-methylpropene and glycinamide, i.e., a cleavage of the peptide bond takes place. However, in the copper(I) system the heterolytic cleavage of the sigma-bond and the reaction of the transient complex with L-Cu2+ compete efficiently with the beta-elimination process. The latter reaction leads to some modification of the amide. We suggest that the formation and decomposition of transients with metal-carbon sigma-bonds may describe an additional pathway for peptide damage induced by aliphatic free radical precursors (e.g., OH., H2O2) in the presence of transition metal ions.
Chromium↗
Prolonged clinical latency and survival of macaques given a whole inactivated simian immunodeficiency virus vaccine.
Simian immunodeficiency virus (SIV) infection of macaques is a useful and relevant model for evaluating candidate human immunodeficiency virus (HIV) vaccines. One important feature of this model is that SIV vaccines can be evaluated for their ability to prevent infection as well as to prevent or delay the onset of AIDS. In the present study, a group of macaques was vaccinated with whole inactivated SIV and challenged with peripheral blood mononuclear cells from an SIV-infected macaque. This challenge represented a rigorous and realistic test of the immunization protocol. All macaques became infected after challenge; however, immunized animals survived significantly longer (P < .03) than naive controls. These data suggest that similar vaccines administered to humans at risk for HIV-1 infection might delay or prevent AIDS even if the vaccine failed to prevent infection.
AIDS Vaccines↗
Brain imaging.
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Attention Deficit Disorder with Hyperactivity↗
Spontaneous substitutions in the vicinity of the V3 analog affect cell tropism and pathogenicity of simian immunodeficiency virus.
Simian immunodeficiency virus (SIV) exists within tissues of infected macaques as a mixture of diverse genotypes. The goal of this study was to investigate the biologic significance of this variation in terms of cellular tropism and pathogenicity. PCR was used to amplify and clone 3'-half genomes from the spleen of an immunodeficiency SIV-infected pig-tailed macaque (Macaca nemestrina). Eight infectious clones were generated by ligation of respective 3' clones into a related SIVsm 5' clone, and virus stocks were generated by transient transfection. Four of these viruses were infectious for macaque peripheral blood mononuclear cells (PBMC) or monocyte-derived macrophages (MDM). Three viruses with distinct tropism for macaque PBMC or MDM were tested for in vivo infectivity and pathogenicity. The ability of these three viruses to infect PBMC and macrophages correlated with differences in infectivity and pathogenicity. Thus, a virus that was infectious for both PBMC and MDM was highly infectious for macaques and induced AIDS in half of the inoculated animals. In contrast, virus that was less infectious for PBMC and not infectious for MDM induced only transient viremia. Finally, a virus that was not infectious for either primary cell type did not infect macaques. Chimeric clones exchanging portions of the envelope gene of the 62A and smH4 molecular clones and a series of point mutants were used to map the determinant of tropism to a 60-amino-acid region of gp120 encompassing the V3 analog of SIV. Naturally occurring mutations within this region were critical for determining tropism and, as a result, pathogenicity of these SIVsm clones.
Amino Acid Sequence↗
Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction.
BACKGROUND: Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). METHODS AND RESULTS: LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly. CONCLUSIONS: In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.
Animals↗
A vascular protective concept in hypertension and heart failure.
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Angiotensin-Converting Enzyme Inhibitors↗
Ventricular remodeling and angiotensin-converting enzyme inhibitors.
The left ventricle can change its size and shape as a result of external load and/or loss of viable myocytes. This process, defined as remodeling, can be adaptive, as in compensatory hypertrophy and dilation secondary to myocardial infarction, or maladaptive in response to long-standing systemic hypertension. In addition to ventricular enlargement and cellular hypertrophy, extensive interstitial collagen deposition also occurs during this remodeling process. The increased fibrous tissue and hypertrophied myocytes can also lead to inappropriate energy production and utilization. Angiotensin-converting enzyme (ACE) inhibitors have the ability to modulate both cellular hypertrophy and collagen deposition. These effects represent, in part, the mechanism by which ACE inhibitors modify ventricular remodeling, the subsequent development and clinical expression of heart failure, and finally, the improvement in the mortality of patients with heart failure.
Angiotensin-Converting Enzyme Inhibitors↗
Two-stage tuberculin skin testing in an HIV-infected population: a preliminary report.
To identify differences in purified protein derivative (PPD) tuberculin positivity rates and to assess the utility of sequential PPD testing among persons with HIV infection, we performed two sequential administrations of 5 tuberculin units of PPD in a group of persons with HIV infection. Eligible patients were skin-tested with the tuberculin using the Mantoux method. Patients who tested < 5 mm of induration were skin-tested seven days later along with Candida and mumps antigens. Of 37 tested patients, only 18 (49%) returned to have the first test read. Using a > or = 5 mm cutoff, 5 (28%) tested positive. Positivity varied markedly between patients with CD4+ cell counts under and at or over 400 cells/mm3 (0% vs. 56%). Among patients who had a reaction to the first test, the reaction was smaller in patients with CD4+ cell counts under 400 than in those with counts at or over 400 cells/mm3 (mean induration: 2.8 vs. 30.4 mm). Positivity was also less frequent in intravenous drug users than in nonusers (9% vs. 57%); these two groups did not differ with respect to CD4+ cell counts. Of the 13 patients who tested < 5 mm, only 8 (62%) kept their appointments to have the second test placed and read. Only 1 of these, a drug user with a CD4+ count of 6 cells/mm3, had a positive reaction with boosting from 4 mm on the first test to 10 mm on the second. These data indicate that PPD testing may be unreliable in screening for tuberculosis infection in persons with CD4+ counts < 400 cell/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
On the mechanism of functional mitral regurgitation.
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Animals↗