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Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 109 records · Page 6Linked to original sources
PubMed1992

Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells.

Catecholamine-regulation of lipolysis and beta-adrenoceptor binding isoterms were studied in human sc and omental isolated fat cells from 24 subjects undergoing elective cholecystectomy. The lipolytic sensitivity of the nonselective beta-agonists epinephrine and isoprenaline as well as the selective agonists norepinephrine (beta 1) and terbutaline (beta 2) was significantly increased 5-10 times in omental fat cells. On the other hand, no regional difference in antilipolytic sensitivity was seen for the alpha 2 agonist clonidine. No regional difference in lipolytic action was seen when measuring the effect of forskolin, (Bu)2cAMP or enprofylline, which act at different postadrenoceptor steps in the lipolytic cascade. Lipolysis data showed no sex differences. A beta 1-pattern was seen in both regions when lipolysis dose-response curves were arranged in order of potency. Radioligand saturation experiments with the nonselective beta-antagonist 125I-cyanopindolol and competition experiments between this radioligand and the selective antagonists CGP-20,712-A (beta 1) and ICI-118551 (beta 2) showed a 2-fold increase in the amount of beta 1- and beta 2-adrenergic receptors in omental as compared to sc fat cells (P less than 0.02). Competition studies with the same radioligand and the nonselective beta-agonist isoprenaline showed no regional differences in terms of receptor affinity (Kd high 10 nM and Kd low 1 microM) or in relative fraction of receptors in the high affinity state (35%). It is concluded that an increased lipolytic sensitivity for beta 1- and beta 2-agonists can be due to an increase in the amount of the two adrenoceptor subtypes in omental fat cells and thereby explain why catecholamines are more lipolytic in omental cells than in sc fat cells.

Abdomen↗
PubMed1991

Immobilized artificial membrane chromatography: rapid purification of functional membrane proteins.

A solid-phase membrane mimetic system, denoted as immobilized artificial membranes (IAM), has been developed and utilized as a novel high-performance liquid chromatography (HPLC) matrix for the first step in the rapid purification of functional membrane proteins. IAM phases consist of monolayers of amphiphilic membrane lipid molecules covalently bonded to a rigid silica particle. These monolayers of lipids have proved remarkably effective for the chromatography of biomolecules. Several cytochrome P450 isozymes, an extremely important family of hydrophobic membrane proteins with a labile heme catalytic center, have been partially purified in functional conformations from rat liver, kidney, and adrenal microsomes on IAM supports. Functionality of purified P450 and P450 reductase has been demonstrated by optical difference spectroscopy, by carbon monoxide binding, and by reconstitution of enzymatic activity in vitro. Other membrane proteins, including rat liver plasma membrane NADH oxidase and ferricyanide oxidoreductase have also been partially purified by IAM HPLC. The methods for purification of these proteins are described.

Adrenal Glands↗
PubMed1991

A novel adrenocorticotropin-inducible cytochrome P450 from rat adrenal microsomes catalyzes polycyclic aromatic hydrocarbon metabolism.

7,12-Dimethylbenz(a)anthracene (DMBA) causes massive ACTH-dependent necrosis of the rat adrenal cortex. This may be related to an ACTH-inducible adrenal microsomal cytochrome P450 that metabolizes polycyclic aromatic hydrocarbons (PAH). The proportions of major monooxygenated products of rat adrenal microsomal DMBA metabolism (DMBA-8,9-diol, DMBA-3,4-diol, and DMBA-phenols) differ significantly from that of P450IA1, the most active PAH-metabolizing P450 in rat liver microsomes. After hypophysectomy, both DMBA metabolic activity and a 57K protein which is distinct from P450XXI disappear from rat adrenal microsomes. ACTH restores both 57K protein and DMBA metabolic activity in hypophysectomized rats almost to the levels in intact untreated rats, but not to levels in ACTH-induced intact rats. The 57K protein has been partially purified from solubilized microsomes in a single step, using detergent elution from a new HPLC matrix consisting of monolayers of phosphatidylcholine covalently bound to a silica support. The resulting P450 preparation contains a single major (57K) band, constituting approximately 70% of the total protein (specific content, 2 nmol P450/mg protein; turnover number, 1.5 nmol DMBA min-1. A rabbit polyclonal antibody raised against this preparation also recognizes a single ACTH-inducible 57K rat adrenal microsomal protein on immunoblots and dose-dependently inhibits DMBA metabolism in solubilized reconstituted rat adrenal microsomes. This 57K P450 is immunochemically distinct from rat P450s of the I, II, III, XVII, and XXI families, but it is immunochemically closely related to a 55K benz(a)anthracene-inducible P450 in the 10T1/2 mouse embryo fibroblast cell line.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Effects of lipolytic and antilipolytic agents on glucose transport in human fat cells.

The effects of lipolytic and antilipolytic agents on glucose transport and glycerol production in isolated human fat cells was investigated. Insulin and various adenylate cyclase inhibitors caused a dose-dependent stimulation of 3-O-methyl glucose transport. The maximum effects were 245 per cent and 100 per cent, respectively. The lipolytic agents isoprenaline, forskolin and dibutyryl cyclic AMP also caused dose-dependent stimulation of 3-O-methyl glucose transport, the maximum effect being about 100 per cent. Enprofylline counteracted the 3-O-methyl glucose transport-stimulating effect of both the lipolytic and antilipolytic agents but altered only the effect of antilipolytic agents on glycerol production. Enprofylline alone had no effect on 3-O-methyl glucose transport activity but stimulated glycerol production. It is on 3-O-methyl glucose transport activity but stimulated glycerol production. It is concluded that stimulation as well as inhibition of lipolysis at different steps in the lipolytic system is associated with acceleration of glucose transport in human fat cell which does not seem dependent upon the lipolysis rate.

Adenylyl Cyclase Inhibitors↗
PubMed1991

[Effects of contrast media products on erythrocyte aggregation. An ex vivo study].

It has been suggested (Fisher and al., Rainiko and al.) that contrast media could interfere with a red blood cell aggregation, low-osmolarity and non ionic contrast media leading to red blood cell aggregates in vitro. Clinical significance of this phenomenon is not known. We have studied 21 consecutive patients admitted in X ray department for pyelography. Sodium and meglumine ioxitalamate (Telebrix 38 R; Guerbet) osmolarity 2 100 mOsm kg--viscosity 8.5 cp at 37 degrees C is used for contrast. Red blood cell aggregation is studied by erythraggregometer Sefam. Samples are collected before (T0), 10 and 30 minutes (T10, T30) after contrast infusion. Hemogram and coagulation parameters are measured in parallel. Results show a significant increase of aggregation times at T10, with a trend towards baseline at T30. Dissociation shear rates follow the same fluctuations. We note a concomitant diminution of both fibrinogen and hematocrit levels, well-correlated with red blood cell aggregation. These results suggest a process of hemodilution which could explain the diminution of red blood cell aggregation with this type of contrast medium.

Adult↗
PubMed1990

Hyperthyroidism and hypothyroidism in monozygotic twins: detection of stimulating and blocking THS receptor antibodies using the FRTL5-cell line.

We present a rare history of monozygotic twin girls who at the age of 10 yr presented with hyper- and hypothyroidism, respectively. Both girls had antibodies against thyrotropin receptors as measured by a radioreceptor assay (230 U/l and 1400 U/l; reference range less than 7 U/l). The sera were further examined in a bioassay, based on a rat thyroid cell line (FRTL5), in which release of cAMP into medium was measured. The TSH receptor antibodies of the hyperthyroid twin displayed a ratio of radioreceptor to biological activity typical of Graves' disease. In contrast, the antibodies of the hypothyroid twin acted as pure antagonists at the TSH receptor level. The occurrence of TSH receptor antibodies in these monozygotic twins suggests a similar pathogenesis of Graves' disease and that of hypothyroidism due to thyroid blocking antibodies.

Adolescent↗
PubMed1990

Bleeding Meckel's diverticulum in an adult.

The diagnosis of a symptomatic Meckel's diverticulum in an adult is uncommon. Still more infrequent is the presentation of a bleeding Meckel's diverticulum after childhood. We present a case report of a 24-year-old male with gastrointestinal hemorrhage secondary to a Meckel's diverticulum containing ectopic gastric mucosa. With the exception of a Meckel's Tc 99m pertechnetate scan, all other diagnostic procedures including Tc 99m-labeled red cell scan and angiography were negative.

Adult↗
PubMed1990

[Effect of contrast media products on the erythrocyte aggregation and deformability in vitro].

It has been suggested that contrast media could interfere with red blood cell aggregation, hyperosmolar media leading to an inhibition of red blood cell aggregation whereas non ionic products might induce a sludge phenomenon. We present an in vitro study accompanying two contrast media: 1) Ioxitalamate of sodium and meglumin (ionic, hyperosmolar). 2) Iopaminol (non ionic). In their effect on hemorheological parameters of red blood cell aggregation. Blood samples have been obtained from 7 healthy donors. Contrast media have been tested at increased contrast media (O.1, 1, 2, 10, 100 mg/ml of Iodine in final concentration). The following parameters have been studied: hematocrit, fibrinogen level, erythrocyte aggregation using the Erythro-aggregometer*, whole blood viscosity at 3 different shear rates (0.87, 18.74, 118 sec.-1) using Low Shear 30*. Deformability of red blood cell was assessed by ektacytometry. Osmolarity was controlled in each sample. Results show an inhibition effect of both contrasts media on red blood cell aggregation. There is a concomitant decrease of blood viscosity at low shear rates. On the contrary, apparent viscosity increases at high shear rates in parallel with the contrast media concentration. This effect is more pronounced with ioxitalamate above a concentration of 10 mg/ml. Ektacytometric parameters are not modified by contrast media and this could indicate a complete reversibility of the media-induced alteration on red blood cell. In order to precise the prothrombotic effect on contrast media, hemorheological studies have to be completed by the assessment of their effect on hemostatic parameters.

Adult↗
PubMed1989

Inhibition of lipolysis by agents acting via adenylate cyclase in fat cells from infants and adults.

The in vitro lipolytic effect of catecholamines is poor during infancy because of enhanced alpha 2-adrenoceptor activity. The mechanisms behind this were investigated in isolated fat cells obtained from 1- to 4-mo-old infants and from adults. The cells were incubated with agents that inhibit lipolysis through distinct receptors coupled to adenylate cyclase via the inhibitory GTP binding coupling protein, Gi. The sensitivity to the alpha 2-adrenoceptor agonist clonidine was 14 times higher in the infant group as compared to the adults, whereas that to an adenosine analogue was 14 times lower. The sensitivities to prostaglandin E2 and nicotinic acid were similar in both age groups. Preincubation of the adipocytes with pertussis toxin abolished the antilipolytic effects of all agents. The density of alpha 2-adrenoceptor binding sites determined with [3H]yohimbine was increased by about 25% in the infants. In conclusion, the antilipolytic sensitivity of adenosine and alpha 2-adrenoceptors develops separately and may play different roles in the regulation of lipolysis in man. Furthermore, the enhanced alpha 2-adrenoceptor sensitivity during infancy seems at least in part to be due to an increase in the number of receptors.

Adenylate Cyclase Toxin↗
PubMed1989

Imaging of the digital arteries: digital subtraction angiography versus conventional arteriography.

A retrospective study of 95 patients was undertaken to compare digital subtraction angiography (DSA) and conventional arteriography of the hand. Eighty patients had conventional angiography and 15 had DSA. In comparison with conventional angiography, DSA is more cost-efficient and facilitates outpatient angiography. It provides images as acceptable as those of conventional angiography. We conclude that intra-arterial DSA is now the procedure of choice for angiographic mapping of the digital arteries.

Adolescent↗
PubMed1988

Adjuvant therapy of breast cancer with or without additional treatment with alternate drugs.

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor-negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor-positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine. All therapy was completed within 1 year. The estimated disease-free rate at 5 years was 68% among patients with Stage II disease and 52% for patients who had Stage III disease. Among patients with estrogen receptor-positive tumors, disease-free survival was significantly prolonged in patients who received methotrexate and vinblastine in addition to tamoxifen (P = 0.04). However, this difference was less pronounced when all randomized patients (including those whose estrogen receptor status was unknown) were included in the comparison. Although most patients experienced moderate to severe granulocytopenia, infectious complications were infrequent. One patient died of septicemia. Congestive heart failure developed in two patients, one of whom had a history of myocardial infarction and congestive heart failure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Phase II evaluation of Ly156758 in metastatic breast cancer.

Fourteen patients with disseminated breast cancer with primary or secondary resistance to tamoxifen were treated with LY156758. There were no complete or partial responses and 1 patient showed a minor response. These data illustrate that LY156758 did not have significant antitumor activity in patients previously treated with tamoxifen therapy.

Breast Neoplasms↗
PubMed1988

Regulation of lipolysis during the neonatal period. Importance of thyrotropin.

We investigated the lipolytic effect of several hormones on isolated human adipocytes obtained at different donor ages. In neonates, noradrenaline and adrenaline had an insignificant lipolytic effect (70% over basal). In this age group only thyrotropin (TSH) had a significant effect in physiological concentrations, and the maximal lipolytic effect (700% over basal) was the same as that of isoprenaline. The lipolytic effect of TSH was the same in premature 4-10-wk-old infants with a gestational age of 27-33 wk as in neonates, but fat cells from infants 4-10 wk old, born at term, showed a significantly lower effect. In children and adults, the lipolytic effect of TSH gradually decreased further and was present only in unphysiological concentrations. The catecholamine-induced lipolysis was pronounced and was similar in children and adults (350% over basal). TSH is the dominating lipolytic hormone in vitro during the neonatal period. Thus, the peak elevation of circulating TSH, which is seen immediately after birth, may be essential to lipolysis during this part of life.

Adenosine Deaminase↗
PubMed1987

Role of alpha-adrenoceptors for adipocyte size in man.

Catecholamines have dual effects on lipid mobilization in man. Lipolysis is stimulated via beta-adrenoceptors and inhibited via alpha 2-adrenoceptors. The relationship between fat-cell size and catecholamine-induced lipolysis (expressed per cell surface area) was investigated in vitro in subcutaneous adipocytes of thirty-five non-obese subjects between 1 month and 45 years of age. Fat-cell volume showed a positive correlation with noradrenaline-induced lipolysis (r = 0.7). Furthermore, fat-cell size showed a negative correlation with the alpha 2-effect of noradrenaline (r = 0.8) but no correlation with the beta-effect of the hormone (r less than 0.1). Although age showed a positive correlation with noradrenaline-induced rate of lipolysis (r = 0.6) it did not contribute to the relationship between cell size and the catecholamine effect. There was no relationship between adipocyte size and the basal (unstimulated) rate of lipolysis (r less than 0.1). In conclusion, ageing in non-obese subjects is associated with enlargement of fat-cell size and enhancement of the lipolytic effect of catecholamines. The latter is due to diminished alpha 2-anti-lipolytic effect of the hormones. This modulation of the alpha 2-adrenoceptor activity may be of importance for the regulation of adipocyte size in man.

Adipose Tissue↗
PubMed1987

Changes in catecholamine-induced lipolysis in isolated human fat cells during the first year of life.

Catecholamine-induced lipolysis in isolated human adipocytes during the first year of life was investigated. During this period fat cell size increased markedly. Basal and catecholamine-induced glycerol release were positively correlated with age when lipolysis was expressed per cell. However, when lipolysis was expressed per unit of cell surface area (micrometer squared), this correlation was observed only for noradrenaline. Basal lipolysis and the effect of the pure beta-agonist, isoprenaline, were identical in infants and adults. From 0 to 2 mo of age noradrenaline had very little lipolytic effect. The addition of the alpha-2-adrenoceptor antagonist, yohimbine, to noradrenaline equalized lipolysis per micrometer squared in infants and adults and the alpha-2-adrenoceptor sensitivity was significantly enhanced in infants. In both groups the lipolytic adrenoceptor was of the beta-1 type. In conclusion, adipocytes from infants have a poor lipolytic response to noradrenaline partly because of the small fat cells but mainly because of an enhanced alpha-2-adrenoceptor activity.

Adenosine Deaminase↗
PubMed1986

Excretion of noscapine in human breast milk.

The excretion of noscapine in human breast milk was studied in 8 lactating women given a single oral dose of 100 or 150 mg after a light breakfast. Serum and milk samples were collected for 24 h after drug intake. Although noscapine is a weak base, only a small amount was excreted in the milk. The median milk/serum ratio was 0.29, range 0.15-0.88. The noscapine dose received by a child during a 24 hour period, when the maternal dose is 50 mg t.i.d., was calculated to be 0.8 (0.4-1.9) micrograms/kg (median and range).

Adult↗