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Biomedical subjects

C Marcus

Publications and source records attributed to C Marcus.

At least 91 records · Page 5Linked to original sources
PubMed1995

Influence of body temperature on thyrotropic hormone release and lipolysis in the newborn infant.

The present study investigated possible interactions between body temperature, lipolysis and thyrotropin (TSH), the only hormone with a documented lipolytic effect in vitro in newborn infants. Healthy infants were either nursed in the usual way (n = 18) or protected from a decrease in body temperature (n = 17) during the first postnatal hour. The infants' axillary temperatures were measured immediately after birth and after 10 and 60 min. Blood samples were collected from the umbilical vein and from the infants 10 and 60 min after birth for analysis of TSH, glycerol, free fatty acids, 3-OH-butyric acid and glucose. We found that the mean (+/- SD) infant axillary temperature was 37.6 +/- 0.4 degrees C immediately after birth. In the routinely nursed infants, body temperature decreased to 37.0 +/- 0.5 degrees C at 10 min (p = 0.01) and to 36.6 +/- 0.4 degrees C at 60 min (p = 0.01); the cold-protected infants maintained their fetal temperature at 60 min of age. There was a four-fold increase in plasma TSH levels at 10 min, independent of the infant's body temperature, and the hormone level remained invariably high at 60 min. Plasma glycerol levels increased progressively at 10 min (p = 0.01) and 60 min (p = 0.01) in both infant groups, but were higher (p = 0.02) in the routinely nursed infants at 60 min. No significant relationship was found between TSH and glycerol levels. Infant body temperature did not affect the levels of free fatty acids, 3-OH-butyric acid or glucose. We conclude that the change in environmental temperature as a result of extrauterine adaptation causes thermal stimulation of the infant's body surface which leads to activation of the hypothalamic-pituitary TSH axis, resulting in maximal TSH release, and thus to induction of the lipolytic process. A decrease in body temperature may be an additive stimulus for further enhancement of lipolysis.

Body Temperature↗
PubMed1995

Growth hormone (GH) treatment up-regulates GH receptor mRNA levels in adipocytes from patients with GH deficiency and Prader-Willi syndrome.

We have investigated the effect of growth hormone (GH) treatment on GH receptor mRNA expression in five prepubertal children with Prader-Willi syndrome and in eight patients with GH deficiency. An adipose tissue needle biopsy was taken before and after 2-4 mo of GH treatment, and RNA was isolated from adipose tissue and from adipocytes. GH receptor mRNA levels were determined by an RNase protection/solution hybridization assay. To further assess the specificity of the assay for GH receptor mRNAs, RNA extracted from human adipose tissue was subjected to Northern blot analysis. GH treatment significantly increased GH receptor mRNA levels in adipose tissue and isolated adipocytes. Our results indicate that GH may have an important role in regulating the GH receptor in humans.

Adipocytes↗
PubMed1995

Effect of glucocorticosteroid treatment on glucocorticoid receptor expression in human adipocytes.

The influence of glucocorticoid excess on expression of the glucocorticoid receptor (GR) and beta-adrenoceptor subtype was studied in isolated adipocytes obtained by sc fat biopsies from 17 healthy individuals. The biopsies were taken before and after 7 days of treatment with 25 mg prednisolone, given orally. GR and beta 1- and beta 2-adrenoceptor messenger ribonucleic acid (mRNA) levels were measured with a solution hybridization assay, and the number of beta 1- and beta 2-adrenoceptor binding sites was determined in radioligand binding experiments. GR protein levels were determined by Western blot analysis using an anti-GR antibody. Both GR protein and GR mRNA levels decreased significantly (P < 0.05) by about 50% after treatment, whereas no significant changes were demonstrated in either beta 1- or beta 2-adrenoceptor mRNA levels. The number of beta 2-adrenoceptor-binding sites, however, increased by 70% after treatment (P < 0.05), whereas the number of beta 1-adrenoceptor binding sites was not affected. The affinity of each receptor subtype was not significantly altered by steroid treatment. In conclusion, an in vivo glucocorticoid excess decreases GR mRNA as well as GR protein levels and selectively increases beta 2-adrenoceptor density in sc fat cells of healthy individuals. This indicates that glucocorticoids modulate human adipose metabolism by altering the expression of regulatory proteins at various mRNA and post-mRNA levels.

Adipocytes↗
PubMed1995

Effects of stimulatory and inhibitory thyrotropin receptor antibodies on lipolysis in infant adipocytes.

TSH is a potent lipolytic hormone for isolated human adipocytes from neonatal subjects. Crude immunoglobulin fractions from sera of patients with Graves' disease, containing stimulatory TSH receptor (TSHR) autoantibodies, significantly increased lipolysis in fat cells from infants, whereas immunoglobulin fraction from a patient with inhibitory TSHR autoantibodies (TBab) blocked TSH-induced lipolysis in a dose-dependent manner. Although TBab totally blocked the maximum lipolysis induced by TSH (10(5) mU/L), no effect was seen on isoprenaline-induced lipolysis. The maximum lipolytic response to TSH was similar to that seen with the beta-adrenoceptor agonist isoprenaline, and there was a similar cAMP increase in response to both stimulators. From these results, it is concluded that the TSHR in infant adipocytes is likely to be coupled to the adenylate cyclase system, and the lipolytic effect of TSH can be simulated by stimulatory TSHR autoantibodies or inhibited by TBab.

Adipocytes↗
PubMed1995

Effects of intranasal glucocorticoids on endogenous glucocorticoid peripheral and central function.

Glucocorticoids are among the most potent antiinflammatory agents that can be used in the treatment of rhinitis. Their mechanisms of action are multiple and complex and a number of reports describe significant systemic effects of locally administered glucocorticoids. In order to evaluate the short-term systemic effects of intranasally administered glucocorticoids, 14 normal healthy subjects were treated with two doses of either budesonide (BUD) or fluticasone propionate (FP) for 2 weeks. Before treatment, at regular intervals during the treatment, 1 week and finally 6 weeks after termination of treatment, the effects on glucocorticoid receptor (GR) and methallothionein (MTIIa) mRNA expression levels were examined in peripheral lymphocytes using a solution hybridization assay. Serum cortisol, osteocalcin and urinary cortisol levels were also determined. An insulin tolerance test (ITT) was performed at the end of the second week of treatment and at the end of the 6-week washout period with no statistically significant change in cortisol response. In peripheral lymphocytes, GR mRNA levels were significantly down-regulated. MTIIa mRNA levels increased significantly. Serum osteocalcin decreased significantly during treatment with both BUD and FP. Serum cortisol decreased after 1 week of treatment whereas urinary cortisol was not affected until the second week of treatment. In conclusion, intranasal glucocorticoids at clinically recommended doses have not only significant systemic effects on adrenal function, but also have an effect on specific gene expression in peripheral lymphocytes. These effects are receptor-dependent, reversible, and according to serum and urinary cortisol levels and ITT, leave the hypothalamic-pituitary-adrenal function intact. Finally, these short-term systemic effects were not associated with any of the noticeable side-effects usually observed during long-term treatment with glucocorticoids.

Administration, Intranasal↗
PubMed1995

[Mycotic aneurysm of the posterior tibial artery and pseudo-phlebitis: contribution of color Doppler ultrasonography].

Mycotic aneurysm of the posterior tibial artery and pseudophlebitis: role of color Doppler sonography A case of a 78-year-old male patient presenting with endocarditis caused by Streptococcus bovis and pseudophlebitis of the left lower limb is described. Color Doppler sonography ruled out thrombophlebitis and showed a large pulsatile mass of the posterior compartment of the leg due to a mycotic aneurysm of the posterior tibial artery. This aneurysm was confirmed by angiography and treated by surgery. The important role of color Doppler sonography for the diagnosis of this particular case is emphasized.

Aged↗
PubMed1994

Growth hormone increases the lipolytic sensitivity for catecholamines in adipocytes from healthy adults.

The lipolytic effect of growth hormone (GH) was investigated in adipocytes obtained during elective surgery from otherwise healthy adults, 18-40 years old. No lipolytic or antilipolytic effect of GH was found when the cells were incubated with GH alone during 30min-6h. When the cells were preincubated with GH during 3h, the lipolytic sensitivity for isoprenaline increased markedly without any change in maximal lipolysis. However, a full effect was only obtained if GH was also present during the incubation with isoprenaline. GH did not alter DB-CAMP, enprophylline, or forskolin-induced lipolysis in human fat cells. In conclusion, GH had no direct lipolytic effect on human fat cells but GH markedly increased the catecholamine sensitivity. The site of the GH effect seems to be in the beta-adrenoceptors or in the Gs coupling protein.

Adipocytes↗
PubMed1994

Lack of evidence for estrogen and progesterone receptors in human adipose tissue.

We have previously presented data indicating the absence of estrogen and progesterone receptors from human adipose tissue by the use of specific antibodies (Abbott) as well as specific ligands. In addition, specific estrogen and progesterone cRNA probes did not hybridize to any mRNA species in either abdominal or gluteal/femoral adipose tissue as demonstrated by solution hybridization and Northern blot. In order to demonstrate even extremely small quantities of gene products we have now used the Polymerase chain reaction-technique to study estrogen- and progesterone receptor gene expression. Sequences corresponding to each specific cDNA were demonstrated indicating small amounts of estrogen- and progesterone receptor mRNA not detected by RNA/RNA or RNA/TNA (total nucleic acids) hybridization assays. The estrogen receptor-regulated gene pS2, however, was not induced by estrogens in human adipose tissue in contrast to a significant increase in pS2 mRNA levels after estrogen exposure to the estrogen receptor(+) cell line MCF7. From these results we conclude that estrogen- and progesterone receptors are absent from human adipose tissue and that the extremely low level of transcription of the corresponding genes is not sufficient to allow translation of the message into functional proteins.

Adipose Tissue↗
PubMed1994

Disturbances of kinaesthesia in patients with cerebellar disorders.

We studied the ability of patients with cerebellar degeneration to perceive differences in kinaesthetic stimuli and compared it with that of normal subjects. All participants were tested for duration, amplitude and velocity sensation. In separate experiments, the responses of muscle spindle afferents and slowly adapting cutaneous mechanoreceptors to the kinaesthetic stimuli were recorded. The performance of patients with cerebellar degeneration was significantly worse than that of normal subjects on the tasks testing for duration and velocity perception. Although both spindle afferents and slowly adapting cutaneous mechanoreceptors were able to provide relevant sensory information during the kinaesthetic tasks, spindle afferents were superior in detecting velocity changes. These results suggest that the cerebellum may be involved in processing sensory signals that are involved in motor control as well as in conscious perception.

Afferent Pathways↗
PubMed1994

Imaging rheumatic joint diseases with anti-T lymphocyte antibody OKT-3.

T lymphocytes play an important role in the pathogenesis of rheumatoid arthritis (RA). Murine monoclonal antibody OKT-3 (IgG2a), known to be specific for T lymphocyte 20 kD glycoprotein CD3 receptor was labelled with 5 mCi 99Tcm and given intravenously (i.v.) to seven RA and two psoriatic arthritis patients following informed consent to identify inflamed synovium. Anterior and posterior whole body scans and specific regional imaging was commenced 20 min later. At 1 h, approximately 20% of 99Tcm was associated with the lymphocytes. In these patients, all 41 asymptomatic joints and 43 joints with mild pain or minimal tenderness had normal scans. All 34 joints with moderate to severe pain had moderate to marked uptake of radioactivity. Two patients experienced shaking chills for 20-30 min within an hour of 99Tcm-OKT-3 infusion. These results suggest that 99Tcm-OKT-3 imaging serves as an objective surrogate for joint inflammation and could be useful as a measurement of therapeutic effectiveness in RA and other diseases with inflamed synovium. The side effect profile may limit the utility of 99Tcm-OKT-3 but other forms of antibodies directed toward lymphocyte subsets may be useful.

Adult↗
PubMed1994

Expression of thyrotropin receptor and thyroid hormone receptor messenger ribonucleic acid in normal, hyperplastic, and neoplastic human thyroid tissue.

In the first part of this study, we examined TSH receptor (TSHR) and thyroid hormone receptor (T3R beta) messenger ribonucleic acid (mRNA) levels in normal, hyperplastic, and neoplastic human thyroid tissue. Tumor specimens from patients with different thyroid carcinomas and thyroid adenomas, and tissues from patients with Graves' disease and from normal thyroid glands were analyzed by solution hybridization and Northern blot using complementary RNA probes. In the second part of the study, mRNA analysis of T3R was extended to include the expression levels of each of the four T3R isoforms alpha 1, alpha 2, beta 1, and beta 2. In neoplastic thyroid tissue such as papillary and follicular carcinomas, the expression of both TSHR and T3R beta mRNA per microgram total RNA was significantly lower than that in normal thyroid tissue. The decrease in T3R beta mRNA was shown to represent a specific and significant decrease in T3R beta 2 mRNA levels in particular, but also in the expression levels of T3R beta 1 mRNA. No differences were found in the expression levels of T3R alpha 1 or -alpha 2 mRNA. Furthermore, no differences in TSHR or T3R mRNA levels were found in thyroid tissue from patients with Graves' disease compared to normal thyroid tissue. It is concluded that the reduction of TSHR and T3R mRNA in specific neoplastic thyroid tissues might be associated with the differentiation state of these tumors and that the decrease in T3R mRNA levels is due to a specific decrease in the expression levels of the T3R beta gene.

Adenocarcinoma, Follicular↗
PubMed1994

Complement, leukocytes, and leukocyte elastase in full-term neonates undergoing cardiac operation.

In 13 neonates undergoing cardiac operations for congenital cardiac defects, complement, leukocytes, and leukocyte elastase were studied during and after cardiopulmonary bypass. All but two neonates received prostaglandin E1 before the operation. The C3d/C3 ratio rose significantly during cardiopulmonary bypass from 0.86 +/- 0.55 to 1.40 +/- 0.56 (mean +/- standard deviation; p < 0.0001). Abnormally elevated C5a levels (18.6 +/- 7.3 micrograms/L) were measured at the end of cardiopulmonary bypass. C4 was not overtly consumed during the procedure. Leukocytes fell from a preoperative value of 10.06 +/- 3.15 x 10(9)/L to 3.21 +/- 0.64 x 10(9)/L after beginning of cardiopulmonary bypass (p < 0.0001) and rose at the end of the procedure from 2.33 +/- 0.67 x 10(9)/L to 7.19 +/- 1.84 x 10(9)/L, after protamine administration (p < 0.0001). Neutrophils fell from a preoperative value of 5.14 +/- 1.18 x 10(9)/L to 1.46 +/- 0.35 x 10(9)/L after beginning of cardiopulmonary bypass and rose at the end of extracorporeal circulation from 1.00 +/- 0.31 x 10(9)/L to 4.10 +/- 1.18 x 10(9)/L, after protamine administration (p < 0.005). Elastase release occurred in all neonates during cardiopulmonary bypass and averaged 331.5 +/- 175.7 micrograms/L. Complement activation and leukocyte stimulation did not correlate with postoperative complications or outcome. This study demonstrates complement activation and leukocyte stimulation in neonates undergoing cardiac operation.

Alprostadil↗
PubMed1993

Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy.

OBJECTIVE: A disturbed energy transfer involving the adenine nucleotide translocator across the inner mitochondrial membrane has been suggested to be one specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. METHODS: Concentrations of adenine nucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were determined. Analysis was performed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from papillary muscles from seven patients operated on for mitral regurgitation. RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%, significantly higher (p < 0.001) than in patients with dilated cardiomyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left ventricular adenine nucleotide translocator mRNA concentrations did not differ from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide translocator mRNA concentrations were significantly increased (p < 0.001). Upregulation was more pronounced in right ventricular than in left ventricular myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p < 0.05). Citrate synthase activity was significantly decreased only in dilated cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit content was significantly higher in mitral regurgitation than in dilated cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and depressed oxidative capacities, dilated cardiomyopathy was specifically characterised by pretranslational upregulation of adenine nucleotide translocator.

Adolescent↗
PubMed1993

Lack of lipolytic response in infants after endotracheal intubation.

The sympathoadrenal response to endotracheal intubation was investigated in nine infants 2-4 months old and in eight adults 23-45 years old at the start of inguinal hernia operations. In both infants and adults, heart rate and diastolic blood pressure increased significantly immediately after intubation. In both groups, moreover, there was a mean (SD) reduction in microvascular blood flow in the abdominal skin (infants -21 (14)%, adults -14 (7)%) and in the adipose tissue (infants -7 (4)%, adults -5 (4)%). However, the plasma glycerol concentration did not increase in the infants whereas it increased in the adults by 50 (12)%. In conclusion, infants and adults showed similar circulatory reactions during endotracheal intubation but the markedly increased lipolysis rate observed in adults was not seen in the infants. This may indicate that catecholamine induced lipolysis in vivo as well as in vitro is poor during infancy.

Adult↗
PubMed1993

Expression of beta 1- and beta 2-receptor genes and correlation to lipolysis in human adipose tissue during childhood.

beta 1- and beta 2-adrenoceptor (bar1 and bar2) mRNA levels were measured in adipose tissue obtained from children (between 1 month and 10 yr of age) and adults during inguinal hernia operations. Bar1 mRNA levels were constant in all age groups studied. In infants and children less than 7 yr old, bar2 levels were twice as high (P < 0.01) as those in adults, and in infants 1-4 months old, bar2 mRNA levels were higher than bar1 levels (P < 0.01). The bar2/bar1 ratio gradually decreased, and in adults, there was 2.3-fold higher bar1 mRNA expression (P < 0.01). In infants 1-5 months old, the lipolytic sensitivity to noradrenaline was 5 times lower (P < 0.05) than that in adults, whereas the sensitivity to adrenaline and isoprenaline was unchanged. The maximal lipolytic response to adrenaline was higher than that to noradrenaline in infants (P < 0.01), whereas the opposite was found in adults (P < 0.01). The lipolytic sensitivity to the bar1-selective agonist dobutamine was not influenced by age, whereas the sensitivity to the bar2-selective agonist terbutaline was 10,000 times higher in infants than in adults. In conclusion, these data indicate subtype-specific developmental changes in bar expression, with higher bar2 mRNA levels accompanied by increased bar2-induced lipolysis during infancy.

Adipose Tissue↗
PubMed1992

The time-dependent increase in the binding of benzo[a]pyrene to DNA through (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide in primary rat hepatocyte cultures results from induction of cytochrome P450IA1 by benzo[a]pyrene treatment.

The proportion and amount of benzo[a]pyrene (B[a]P) that binds to DNA through the carcinogenic (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide [(+)-anti-BPDE] increases with time of exposure to B[a]P in cell cultures derived from a number of species. Pretreatment of primary rat hepatocyte cultures for 12 h with 1 microgram B[a]P/ml medium increased the subsequent metabolism of [3H]B[a]P by 47% and [3H]B[a]P-DNA binding by 53% compared with acetone-pretreated hepatocytes. The amount of (+)-anti-BPDE bound to DNA in the B[a]P-pretreated hepatocytes increased 175%. B[a]P pretreatment also increased DNA-binding 2-fold in hepatocytes treated with [3H]7,8-dihydroxy-7,8-dihydro-B[a]P but had no effect on DNA binding in cells treated with anti-B[a]P-7,8-diol-9,10-epoxide. Western blotting showed that cytochrome P450IA1, which was not detectable prior to B[a]P treatment, was selectively increased by B[a]P treatment. A monoclonal antibody that specifically inhibits cytochrome P450IA1 reduced the binding of B[a]P to DNA by greater than 90% in microsomal preparations from B[a]P-pretreated hepatocytes. These results indicate that the time-dependent increase in the formation of (+)-anti-BPDE-DNA adducts results from an increase in the amount and proportion of B[a]P metabolized to this ultimate carcinogen by P450IA1 that is induced by the B[a]P treatment. The importance of P450IA1 induction by the B[a]P for its activation to this ultimate carcinogenic metabolite suggests that long-term exposure of cells to B[a]P could result in activation of a higher proportion of the B[a]P to the carcinogenic (+)-anti-BPDE.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗