Search PubMed⌕ Search

Biomedical subjects

M Sobel

Publications and source records attributed to M Sobel.

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

Biochemical mechanisms of tumor invasion and metastasis.

Cancer invasion and metastases is a complex multi-step process. In order for a tumor cell to successfully traverse all the steps of this process and initiate a metastatic colony, it must express the right combination of gene products. Such gene products may include proteins which regulate cell interaction with the basement membrane and cell motility. Tumor cells attach to the basement membrane glycoprotein laminin via the cell surface laminin receptor. The human laminin receptor was purified and molecularly cloned. The level of laminin receptor mRNA in a variety of human carcinoma cells correlated with the number of laminin receptors on the surface of these cells. Following attachment to the basement membrane, the tumor cell next secretes proteases which may degrade type IV collagen. A genetic linkage between type IV collagenase secretion and metastases was collagen. A genetic linkage between type IV collagenase secretion and metastases was studied using our new genetic system for inducing metastases by employing the ras oncogene. Following attachment and local proteolysis, the third step of invasion is tumor cell motility. We have isolated a tumor cell autocrine motility factor (AMF). This factor is secreted by the tumor cells and binds to a cell surface receptor, resulting in a profound (greater than 100 x) stimulation of cell locomotion. AMF may play a major role in the autonomous invasive behavior of tumor cells.

Animals↗
PubMed1987

Coagulation responses to heparin in the ischemic limb: assessment of thrombin and platelet activation during vascular surgery.

In 11 men undergoing infrainguinal bypass surgery, simultaneous blood samples were analyzed by use of sensitive markers of thrombin activity (fibrinopeptide A, FPA) and platelet behavior (beta-thromboglobulin, beta-TG), as well as conventional clotting times. FPA levels were consistently higher in the venous outflow from the ischemic limb compared with the arterial inflow (p less than .01), while no venoarterial difference was noted for beta-TG. This suggests that there is increased thrombin generation, but not platelet activation localized to the ischemic limb. After a mean dose of 6800 units of heparin given during surgery, FPA levels fell significantly (p less than .03), and the activated clotting time (ACT) was prolonged to 230 to 260 sec, but beta-TG levels did not change. Anticoagulation during lower extremity vascular surgery may be usefully monitored by the activated clotting time because an ACT longer than 250 sec is correlated with lower FPA levels (less than 10 ng/ml), reflecting significant inhibition of coagulation.

Blood Coagulation↗
PubMed1986

Dextran 40 reduces heparin-mediated platelet aggregation.

Using platelet aggregometry, we investigated the in vitro efficacy of dextran, mean MW 40,000, in reducing the heparin-mediated platelet aggregation seen with the syndrome of heparin-associated thrombocytopenia (HAT). Six patients with the clinical syndrome of HAT were studied who had a plasma factor which induced aggregation of normal platelets in the presence of heparin. At a final concentration of 2% (20 mg/ml) Dextran 40 reduced heparin-stimulated aggregation by 60.5 +/- 36% (SD) in mixtures of normal platelet-rich plasma/HAT patient plasma. In contrast, the same dextran concentration reduced ADP-stimulated aggregation of normal platelet-rich plasma by only 18.6 +/- 12%. This selective inhibition of heparin-mediated aggregation by dextran was highly significant (P less than 0.005, Wilcoxon rank sum). Whereas protamine abolished heparin's anticoagulant and platelet aggregating activity, dextran had no effect on heparin's anticoagulant properties. These data show that Dextran 40 selectively blocks heparin-mediated aggregation in vitro, perhaps by blocking heparin binding to the platelet membrane. This study suggests that dextran may be a clinically useful adjunct in the treatment of HAT, and describes a simple method for testing the efficacy of drugs in the treatment of HAT.

Adenosine Diphosphate↗
PubMed1986

Statistics of natural populations. III. Sequential sampling plans for the estimation of gene frequencies.

In previous work several models have been developed for genetic surveys of natural populations. Parents of unknown genotype are collected from a natural population, polymorphic at a single genetic locus. From each of these N cryptic parents a number of offspring are identified for their genotype. Our problem is to select an efficient offspring sampling plan for estimating the frequency of an allele in the cryptic adult population based on the N family profiles of juvenile genotypes. A criterion called the information per unit cost of observation is introduced to evaluate sequential sampling plans, in which the number of offspring per family examined is random. Some simple, practical schemes for stopping the sampling of offspring from a collected parent are introduced; one example is stopping when: (i) the offspring are definitive about the parental genotype(s) for the first time; (ii) a fixed number of one genotype only is seen; or (iii) a fixed maximum feasible number of offspring have been genotyped. This sampling scheme is recommended. For each sampling scheme, the best linear unbiased estimator and the sequential maximum likelihood estimator of the allele frequency are characterized. From the moments of these estimators, it is then possible to tabulate efficient sequential sampling plans, which are better (in the sense of information per unit cost), just as simple, and less costly than corresponding fixed sampling plans in use.

Alleles↗
PubMed1986

Contralateral neurologic symptoms after carotid surgery: a nine-year follow-up.

A study was undertaken to observe the long-term clinical behavior of the contralateral, asymptomatic carotid artery of patients after unilateral carotid endarterectomy (UCE). A consecutive series of 182 patients undergoing UCE were followed up for 1 to 9 years (mean 4.2 years). The operated artery was symptomatic in 169 cases (92.8%) whereas in 13 (7.2%) it was asymptomatic but stenotic. Follow-up included an accounting of all hemispheric or focal neurologic events in the territory of the nonoperated artery, as well as associated cardiovascular risk factors. A total of 11 patients (6%) suffered stroke (CVA) and six (3.3%) had transient ischemic attacks (TIAs) in the distribution of the nonoperated carotid artery. By life-table analysis, major neurologic symptoms developed in 11.6% of patients within 5 years. Hypertension was an important prognostic factor: significantly more hypertensive patients had late contralateral neurologic symptoms (p less than 0.05, chi square). The cumulative incidence of CVA and TIA in these patients was 17.3% by life-table analysis at 5 years vs. 9.1% for normotensive patients. Since only a small proportion of the patients studied had a high-grade stenosis of the nonoperated artery, no conclusions could be made regarding its prognostic importance. The relevant published studies are discussed and compared with this report. Guidelines for the management and follow-up of the patient after UCE are discussed.

Adult↗
PubMed1985

Isolation and characterization of the human fibrillar collagen genes.

In order to elucidate some of the mechanisms leading to the pathological expression of the human fibrillar collagens, as well as to understand the evolution of these loci, specific cDNA and genomic clones have been isolated. The primary structure of the COOH-terminal propeptide of the four collagen chains and either part or the entire exon/intron arrangement of the genes have been determined. Interspecies and pairwise comparison revealed that the four loci have evolved at slightly different rates, maintaining, however, remarkably similar exon/intron arrangement. The fibrillar genes, albeit sharing the same elaborate structure, exhibit different sizes that correlate with the average length of their intron sequences, possibly because of their different chromosomal origin.

Animals↗
PubMed1985

Malignant transformation and tumor promoter treatment increase levels of a transcript for a secreted glycoprotein.

The major excreted protein of transformed mouse fibroblasts, a secreted, mannose 6-phosphate-containing glycoprotein, is induced in nontransformed cells by a variety of transforming agents, by phorbol esters, and by platelet-derived growth factor. We report here the molecular cloning of the cDNA encoding this protein and demonstrate that its induction is a consequence of enhanced mRNA levels for major excreted protein in both tetradecanoyl phorbol acetate-treated 3T3 cells and 3T3 cells transformed by a variety of retroviruses or retroviral oncogenes. These results indicate that tumor promoters and retroviral transformation might share a common pathway of action in cultured cells and that major excreted protein is a molecular marker for the growth response of cells to these agents.

Animals↗
PubMed1984

Phototherapy for neonatal jaundice: in vitro comparison of light sources.

Phototherapy results in the conversion of bilirubin to more water-soluble isomers. Six clinically used phototherapy lamps which differ in their emission spectra have been compared in their ability to produce configurational and structural isomers of bilirubin in vitro. For all of the lamps, the initial rate of configurational isomerization was highly correlated (r = 0.969) with the intensity of irradiation falling within the bilirubin absorption band. The percentage of the total bilirubin converted to the configurational isomer at equilibrium was dependent upon the spectral distribution of the lamp, and was greatest (26.2 +/- 1.3%) with the special blue lamp, which has a narrow spectral output centered at 445 nm. The rate of formation of the structural isomer, lumirubin, was generally dependent upon the intensity of irradiation within the bilirubin absorption band.

Bilirubin↗
PubMed1981

Circulating platelet products in unstable angina pectoris.

In 19 patients with unstable angina pectoris at rest, plasma levels of the platelet-derived proteins beta-thromboglobulin and platelet factor 4 were significantly elevated in blood samples obtained during or within 4 hours after episodes of angina, but were usually normal during quiescent intervals. Plasma levels of the arachidonic acid metabolite thromboxane B2 were less clearly related to angina, and there was no association of angina with levels of the coagulation product fibrinopeptide A. This demonstration of an association of platelet activation and secretion with unstable angina pectoris by radioimmunoassay of circulating platelet constituents offers a new approach to assessment of therapy in ischemic heart disease and suggests that agents that alter platelet function should be evaluated in patients with unstable angina.

Adult↗
PubMed1981

Preservation of platelet function and number by prostacyclin during cardiopulmonary bypass.

Thirty-four dogs underwent total cardiopulmonary bypass for 1 or 2 hours with a bubble oxygenator and cardiotomy suction. The dogs were divided into three groups: control dogs which received heparin alone, dogs which received prostacyclin (PGI2) and heparin, and dogs which received prostacyclin alone. PGI2 was given as a bolus (6 to 60 microgram) and then as a constant infusion (0.2 to 0.8 microgram/kg/min) in the venous outflow line. The pump flows were equal in the three groups. PGI2 as a bolus led to transient hypotension, and 60 microgram reduced cardiac output temporarily. During cardiopulmonary bypass, dogs treated with prostacyclin and heparin had low mean arterial perfusion pressures which responded to fluid infusion or phenylephrine. After 1 hour of cardiopulmonary bypass and reversal with protamine, dogs treated with prostacyclin and heparin had shorter bleeding times (p < 0.02) and better platelet function than control animals. After 2 hours, they had normal platelet number, but only half showed preservation of platelet function. When heparin was omitted, PGI2 preserved platelet number, but consumption coagulopathy developed, with prolonged prothrombin, partial thromboplastin, and bleeding times and decreased fibrinogen levels. PGI 2 preserves platelet number and function but may cause hypotension, and it cannot replace heparin in cardiopulmonary bypass.

Animals↗
PubMed1980

Further observations on a 13qXp translocation associated with retinoblastoma.

In a patient with a 13qXp translocation and retinoblastoma the band associated with retinoblastoma (13q14) was clearly translocated intact to the X chromosome rather than being the breakpoint of the translocation. Genetic inactivation of the derivative X chromosome shown by late labeling and cell hybridization techniques in the predominance of cells indicated a functional monosomy for this segment as the most likely predisposing factor in producing retinoblastoma.

Chromosomes, Human, 13-15↗
PubMed1980

Elevated plasma fibrinopeptide A and thromboxane B2 levels during cardiopulmonary bypass.

Patients who underwent operations in which cardiopulmonary bypass was used had elevations of plasma fibrinopeptide A which did not return to normal during bypass despite conventional heparin anticoagulation, suggesting inadequate heparin dosage and continued thrombin activity during the operation. Patients who underwent aortocoronary artery grafting had high plasma thromboxane B2 levels and a rapid fall in platelet count at the onset of extracorporeal circulation. Thromboxane elevations were less marked in patients who underwent valve replacement. Platelet aggregation and coronary artery constriction secondary to thromboxane production may contribute to the morbidity of cardiopulmonary bypass.

Adult↗
PubMed1979

National programme for prevention of the recurrence of neural tube defects.

Mothers who since 1970 gave birth to children with anencephaly or spina bifida in Hungary are informed about the recurrence risk, the possibility of prevention and about the four institutes where alpha-feto-protein determination is done. In one of these institutes the examination was recommended to 175 women of whom 158 availed themselves of the opportunity. The outcome of their pregnancy is now known in 131 cases. Of these, in 101 the examination was performed because of previous occurrence of anencephaly-spina bifida. High concentration (400, 200, 140 micrograms/ml) were found in 3 cases; they were due to anencephaly (selective induced abortion), severe spina bifida (liveborn) and macerated fetal death. The examination yielded values above the 99% confidence limit in the given gestational week in further 9 cases. The elevated values were due to twinning in 2 cases, to closed spina bifida in 1, and to fetal death in 1 case. The slightly elevated alpha-fetoprotein in 4 of them may have been due to chance.

Amniotic Fluid↗