Gösta Enberg

Specific binding of human growth hormone but not insulin-like growth factors by human adipocytes.

Binding of human GH (hGH) and insulin‐like growth factors I and II (IGFI and II) to isolated human adipocytes from adult subjects was studied. Binding equilibrium for hGH at 24°C was reached at 120 min and half‐maximal specific binding at 6–8 . Apparent K a was 2.1 × 109 M−1 and B max 7.3 × 10−11 M/106 cells. The human fat cellgrowth hormone receptor recognized neither bovine, ovine or rat GH nor human prolactin or placental lactogen. No specific receptors for human IGFII could be demonstrated. Thus, human adipocytes do not possess IGF receptors but have specific GH receptors which recognize hGH but not GH from lower species.

IGF-II binding on human lymphoid cells: demonstration of a common high affinity receptor for insulin like peptides.

We have studied the binding of 125I-GF-II to the IM-9 human lymphoid cell line, and to human placental membranes. All of IGF-II radioligand binding to IM-9 cells, and half of the binding to human placental membranes is to a previously unrecognized common (Type-III) high affinity receptor site for insulin-like peptides, in which IGF-I and IGF-II are equipotent and insulin only slightly less potent. This common receptor represents another mechanism by which insulin, and the somatomedins can exert biological action.

Enhancement of insulin-like growth factor 2 receptors in glioblastoma

The somatomedins (IGF-1/IGF-2) are a family of growth-promoting hormones which have been identified in the human central nervous system where their specific receptors are distributed. The present study identified somatomedin receptors in glioblastoma and compared them with those found in normal brain. A significant enhancement in the binding of 125I-IGF-2 but not 125I-IGF-1 to glioblastoma membranes was found. A fourfold increase in IGF-2 receptor concentration was observed. These findings indicate enhanced expression of the IGF-2 receptor in glioblastoma.

Julius – a template based supplementary electronic health record system

BackgroundEHR systems are widely used in hospitals and primary care centres but it is usually difficult to share information and to collect patient data for clinical research. This is partly due to the different proprietary information models and inconsistent data quality. Our objective was to provide a more flexible solution enabling the clinicians to define which data to be recorded and shared for both routine documentation and clinical studies. The data should be possible to reuse through a common set of variable definitions providing a consistent nomenclature and validation of data. Another objective was that the templates used for the data entry and presentation should be possible to use in combination with the existing EHR systems.MethodsWe have designed and developed a template based system (called Julius) that was integrated with existing EHR systems. The system is driven by the medical domain knowledge defined by clinicians in the form of templates and variable definitions stored in a common data repository. The system architecture consists of three layers. The presentation layer is purely web-based, which facilitates integration with existing EHR products. The domain layer consists of the template design system, a variable/clinical concept definition system, the transformation and validation logic all implemented in Java. The data source layer utilizes an object relational mapping tool and a relational database.ResultsThe Julius system has been implemented, tested and deployed to three health care units in Stockholm, Sweden. The initial responses from the pilot users were positive. The template system facilitates patient data collection in many ways. The experience of using the template system suggests that enabling the clinicians to be in control of the system, is a good way to add supplementary functionality to the present EHR systems.ConclusionThe approach of the template system in combination with various local EHR systems can facilitate the sharing and reuse of validated clinical information from different health care units. However, future system developments for these purposes should consider using the openEHR/CEN models with shareable archetypes.

The specificity of the human IGF-2 receptor.

The specificity of the type 2 insulinlike growth factor (IGF) receptor is evaluated in human placenta membranes and the human cell line K562. K562 cells have type 2 but not type 1 IGF receptors. Native IGF-2 isolated from human plasma and synthetic IGF-2 were equipotent in competing with labeled IGF-2 in both systems. Pure IGF-1 isolated from plasma, synthetic IGF-1 and recombinant IGF-1 could not crossreact with the type 2 IGF receptor in concentrations up to 1 microgram/ml in both systems. Studies on placenta membrane were done in the presence of 300 ug/ml insulin to block the type 1 IGF receptors. It is concluded that IGF-1, as well as insulin, cannot crossreact with the human type 2 IGF receptor.

The Presence of Normal Levels of Serum Immunoreactive Insulin-like Growth Factor 2 (IGF-2) in Patients with Down's Syndrome

The present study was performed to further investigate the levels of somatomedins in Downs syndrome (DS). The results show that the serum levels of immunoreactive insulin-like growth factor 2 (RIA-IGF-2) in patients with DS is within the normal adult range. No age variation among the patients was observed. Since we earlier reported a deficiency of immunoreactive insulin-like growth factor 1 (IGF-1) in DS patients, present study showing normal RIA-IGF-2 levels suggests a selective deficiency of IGF-1 in DS.

The binding of insulin-like growth factor II to the erythroleukemia cell line K562

The erythroleukemia cell line K562 was previously shown to have specific binding sites for insulin but not for insulin-like growth factor I (IGF-I). In this study the presence of specific receptors for insulin-like growth factor II (IGFqI) is established. Scatchard analysis of the competition curve for IGF-II disclosed a non-cooperative binding kinetic with a calculated affinity constant of 2.4×108 M−1 and a receptor number of 4.8×l04 sites/cell. IGF-I displayed 10% crossreactivity over the IGF-II receptor but insulin did not crossreact at all. Instead insulin, present in high concentrations, enhanced the binding of IGF-II. The presence of IGF II but not IGF-I receptors makes t h e K562 cell line suitable for studying properties of the type-2 receptor.

Degradation of somatomedins by the thioredoxin system.

Insulin Degradation Thioredoxin Insulin‐like growth factor I Insulin‐like growth factor II

An Effective Method for the Separation of Insulin-like Growth Factors 1 and 2 During the Purification Process

The separation of human insulin-like growth factors hIGF-1 and hIGF-2 was greatly improved by an additional purification step using the cation exchanger Mono-S (FPLC) compared to previous studies. Cross-reactions between hIFG-1 and hIGF-2 were strongly reduced. The more highly purified hIGF-1 had a cross-reaction of less than 1% in the RIA for hIGF-2, and was equivalent to recombinant hIGF-1. The pure hIGF-2 had a cross-reaction of less than 1% in the RIA for hIGF-1. In the human placental hIGF-2 radioreceptor assay, the hIGF-1 polypeptide competed less than 1% with hIGF-2 when the type 1 IGF receptor was blocked with insulin.