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Biomedical subjects

E Hell

Publications and source records attributed to E Hell.

At least 37 records · Page 2Linked to original sources

Plasma leptin levels: interaction of obesity with a common variant of insulin receptor substrate-1.

Obesity is associated with insulin resistance and other major cardiovascular risk factors. A common amino acid polymorphism at codon 972 of the insulin receptor substrate-1 (IRS-1) has been shown to interact with obesity in the expression of insulin resistance. The plasma concentration of the adipocyte-specific hormone leptin is increased in obesity and is correlated with adipose tissue mass. Because in vitro studies demonstrated inhibitory effects of leptin on insulin signaling, leptin may be involved in obesity-associated insulin resistance. To gain insight into the relationship between insulin and leptin in obesity, we studied plasma leptin levels and several cardiovascular risk factors, as well as their modification by the IRS-1 codon 972 genotype, in 156 obese individuals and 131 lean control subjects. In both groups, 10% of the subjects were heterozygous for the IRS-1 codon 972 variant. Obese individuals harboring the IRS-1 variant displayed significantly lower plasma concentrations of leptin than obese subjects without the polymorphism (means, 26.7 versus 37.8 ng/mL, P<0.0293). In a subgroup of obese patients, leptin mRNA abundance was measured in the adipose tissue and was significantly lower in carriers of the IRS-1 variant than in subjects with the wild-type variant (P<0.0291). Our data suggest that insulin signaling influences plasma leptin concentrations at the mRNA expression level and argue against leptin as a major causative factor of insulin resistance.

Adult↗

Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus.

Uncoupling protein-1 (UCP-1) activity in brown adipose tissue increases thermogenesis, contributes to facultative energy expenditure in humans, and has been implicated in the pathogenesis of rodent obesity. To determine genetic factors controlling UCP-1 expression in humans, we measured intra- and extraperitoneal UCP-1 mRNA abundance levels by a competitive RT-PCR method and compared expression levels with common sequence variations in the beta3-adrenergic receptor gene and the distal UCP-1 gene promoter in obese human subjects. While median and average UCP-1 mRNA levels in both the intra- and extraperitoneal tissue were lower in subjects heterozygous for the Trp64Arg mutation in the beta3-adrenergic receptor gene, this difference was not statistically significant. However, a strong association of intraperitoneal UCP-1 mRNA abundance with the UCP-1 gene polymorphism at -3826 relative to the transcription start site was observed that explained 19.3% of the interindividual variability. The minor allele imparted a dose-dependent reduction on UCP gene expression. The importance of sequence variations at the UCP-1 gene locus as a common source of UCP-1 mRNA abundance variability was supported by allele-specific expression studies utilizing a newly identified polymorphism in exon 2 of the UCP-1 gene that predicts a substitution of alanine by threonine. In four subjects heterozygous for the -3826 polymorphism, the mRNA species transcribed from the wild-type allele accounted for 63+/-6% percent of total intraperitoneal mRNA abundance. In one subject homozygous for the minor promoter allele, wild-type mRNA was also more abundant than variant mRNA. Thus, the UCP-1 polymorphism at -3826 is probably only a marker for a frequent mutation causing reduced mRNA expression.

Adipose Tissue↗

Human obese gene expression: alternative splicing of mRNA and relation to adipose tissue localization.

BACKGROUND: The adipocyte-specific protein leptin signals the size of the adipose tissue mass to hypothalamic regions, thereby influencing food intake and energy metabolism. Human obesity is often associated with high leptin levels implying leptin resistance or defective leptin function. Two leptin mRNA species differing only by the presence or absence of a CAG codon encoding glutamine at position 49 of the mature protein arise from alternative splicing owing to two splice acceptor sites immediately following each other at the intron 2 - exon 3 junction. Since glutamine 49 is part of a highly conserved region, we studied possible functional implications of alternative splicing for human obesity. METHODS: We determined, in lean and obese individuals, the relative abundance of both mRNA species in intra- and extraperitoneal adipose tissue in relation to ob gene transcript abundance and plasma leptin levels. RESULTS: Leptin mRNA levels in adipose tissue and concentrations of leptin in plasma were significantly higher in obese subjects than in controls. In both obese and control subjects, leptin mRNA levels were higher in extraperitoneal than in intraperitoneal adipose tissue. Furthermore, leptin mRNA abundance correlated with average fat cell size. In all tissue samples, the predominant ob gene transcript contained the codon for glutamine 49 and the molar ratio of the two leptin mRNA species was similar in patients and controls. No correlation was observed between splice site usage and leptin mRNA abundance or leptin concentration in plasma in our study group. CONCLUSIONS: Differences in the primary structure of leptin due to the presence or absence of glutamine 49 are unlikely to contribute to the apparent 'leptin resistance' commonly observed in obese individuals.

Adipocytes↗

Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans.

The mitochondrial uncoupling protein (UCP), which is exclusively expressed in brown adipose tissue, regulates energy expenditure in rodents but its importance in the energy homeostasis of adult humans is uncertain. To study associations of UCP gene expression with human obesity, we determined, by a competitive reverse transcription-polymerase chain reaction assay, UCP mRNA expression levels in intra- and extraperitoneal adipose tissues of 79 obese subjects and 17 lean controls. UCP mRNA and internal standard RNA were reverse transcribed and coamplified in one reaction in which the same primers were used. The signal intensities of UCP mRNA products were compared with the signal intensities of standard RNA products to quantify UCP mRNA abundance. UCP mRNA was detected in all intra- and extraperitoneal adipose tissues studied. In both obese and non-obese subjects, UCP mRNA abundance was higher in the intraperitoneal than in the extraperitoneal tissue (P < 0.001). Compared to lean controls, morbidly obese subjects showed a significantly lower age- and gender-adjusted UCP mRNA expression level in the intraperitoneal adipose tissue (3.467 +/- 2.483 vs. 6.917 +/- 4.292 amol/fmol beta-actin mRNA; mean +/- SD, P < 0.002), while UCP mRNA abundance in extraperitoneal adipose tissue did not differ between obese and nonobese subjects. These data are consistent with reduced energy expenditure in obesity, but it remains to be determined whether the association of decreased intraperitoneal UCP mRNA expression with obesity status reflects a causal contribution of brown adipose tissue function to the pathogenesis of obesity.

Adipose Tissue, Brown↗

Adjustments and Leak Detection of the Adjustable Silicone Gastric Band (ASGB) and Lap-Bandtrade mark Adjustable Gastric Band (LAGB) System.

BACKGROUND: The detection of a leakage in the system of the adjustable silicone gastric band (ASGB) may be difficult. Gastrografin injection into the port should be avoided because it acts like a glue and blocks the system. METHODS: A syringe containing saline and a syringe containing Thallium-201 chloride is connected to the 4-way stopcock which is connected to the needle. The needle is pushed into the port. The position is confirmed by injection and aspiration of saline. 2 ml of TL-201 chloride (74 MBp) is injected to locate the leakage in the system with planar images with a gamma camera (Elscint SP 6), 30 min, 2, 3, and 24 h after injection. RESULTS: The original ASGB was provided with an injection reservoir which, in our series, was found to be leaking in four cases (3%). CONCLUSIONS: Our technique for adjustment and leak detection appears to be simple and effective. Band-related problems such as reservoir leak should disappear with improvement of the material.

Journal Article↗

[10 years experience with vertical banded gastroplasty for operative therapy of morbid obesity].

Since 1985 vertical banded gastroplasty has been performed in a consecutive series of 300 morbid obese patients. Two years after operation the average weight loss was 46 kg or 67% of the initial overweight. There was one postoperative and one late death. The reintervention rate was 2% per year for the first 5 years. In the treatment of morbid obesity vertical banded gastroplasty is an effective procedure, rapid and simple to perform and without irreversible changes of the digestive tract.

Adolescent↗

Local vs Systemic Antibiotics to Decrease Wound Complications following Vertical Banded Gastroplasty: Results of a Prospective Randomized Trial.

BACKGROUND: Obesity is generally regarded as one factor predisposing to wound infection. Most reports of infection rates range from I to 16% for similar procedures. In our department the wound infection rate for morbidly obese patients was 12% without perioperative antibiotics. METHODS: In a prospective randomized study we compared local gentamicin-collagen fleece application in the subcutaneous layer with patients receiving a perioperative single I.V. dose of amoxicillin-clavulanic acid 2.2 g. We examined the results of different perioperative management of antibiotics on 50 morbidly obese patients who underwent vertical banded gastroplasty from March 1993 to August 1994. The fascial, subcutaneous and skin closure technique were identical in the two groups. For both groups we used a closed-suction system to drain the bottom of the deep subcutaneous layer. On the third postoperative day, the subcutaneous drains were removed. Patients stayed in hospital an average of 10 days. They had follow-up visits after 1, 3 and 6 months, and then yearly. RESULTS: None of the 50 patients developed a wound infection, hematoma, or seroma in the hospital. During the follow-up (median 6 months), no patient developed a wound abscess. CONCLUSIONS: We believe that perioperative antibiotic management is an important factor in obtaining a low infection rate.

Journal Article↗

[Effects of surgical therapy of extreme obesity on physical and psychological outcome].

More than 400 patients with morbid obesity were treated surgically in our unit over the past 18 years. Three different methods (intestinal bypass, bilio-intestinal shunt and vertical banded gastroplasty) were used. In order to assess any postoperative increase in life quality and to compare the three different techniques, 25 matched patients from each group were followed up and the findings compared with a group of non-operated morbidly obese persons. Psychological tests were also supplied. Irrespective of the technique performed a significant increase in quality of life was obtained in 75% of the cases.

Activities of Daily Living↗

[Gastroplasty in the treatment of morbid obesity].

A series of 90 gastroplasty operations based on Eckhout's vertical banded procedure are described. The average weight loss at follow up 2 years postoperatively was 66%. There were no operative or late deaths nor any serious complications. The constricting Gore-Tex band had to be lengthened in 3 cases of outlet stenosis and shortened in another 3 cases of stomal dilatation. In one case the patient failed to lose weight due to a large initial pouch volume.

Adult↗

Psoralen photochemotherapy of psoriasis.

The value of PUVA therapy in selected patients with severe psoriasis has been confirmed. Suppression of the disease was incomplete in those patients whose disease was unstable, with associated seborrhoeic dermatitic features. No consistent change in the proportion of epidermal cells in DNA synthesis could be demonstrated during regression of the psoriasis as a result of PUVA therapy.

Adult↗

The initiation of epidermal wound healing in cuts and burns.

An apparatus to produce shallow linear burns is described. The burns contained about the same amount of damaged tissue as a shallow cut. The initiation of healing in cuts and burns on guinea-pig ears was studied using an 3H-thymidine and autoradiographic technique to determine the number of cells in DNA synthesis in epidermis adjacent to the wound. Cuts caused epidermal cells to enter DNA synthesis rapidly; the maximum response was 1 day after injury. Thus response was delayed in burns and the maximum was not seen until at least 3 days after burning. Extracts of normal skin stimulated epidermal DNA synthesis, whereas extracts of burned skin did not. Possible mechanisms affecting the delay in the healing of burns are discussed.

Animals↗

The effect of the activity of psoriasis on the response to autologous ground skin extract.

The effects of autologous extracts of involved and macroscopically uninvolved psoriatic skin on epidermal DNA synthesis have been studied. Previous reports of inhibition of DNA synthesis were confirmed but in a number of patients a stimulant, rather than an inhibitory effect, was observed. The stimulant effect was only present when the disease was in an acute, eruptive phase and was more marked in the involved than in the macroscopically uninvolved skin.

Adult↗