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Biomedical subjects

R Humbel

Publications and source records attributed to R Humbel.

At least 19 recordsLinked to original sources
PubMed2002

Anti-Ro52 reactivity is an independent and additional serum marker in connective tissue disease.

OBJECTIVE: To determine whether anti-Ro52 is an independent serum marker in connective tissue disease. METHODS: Over a two year period, 1727 consecutive antinuclear antibody (ANA) positive serum samples were analysed in parallel by double immunodiffusion with thymus/spleen nuclear extract and by line immunoassay with recombinant Ro52, recombinant La/SSB, and natural Ro60. Sera that were only reactive towards Ro52 were further analysed by a variety of additional anti-SSA/Ro detection methods and by specific anti-Ro52 and anti-Ro60 assays. Natural purified SSA/Ro was analysed by immunoblot and protein sequencing. RESULTS: Analysis of natural purified SSA/Ro (Immunovision, Springdale, AR) showed only Ro60 and no immunoreactive Ro52. Consequently, assays based on this substrate only identify sera with anti-Ro60 reactivity. Twenty serum samples showed anti-Ro52 without anti-Ro60 and anti-SSB/La on line immunoassay. By additional testing, 2/20 sera were found positive for anti-Ro60 reactivity. The remaining 18 sera were not identified by any of the classical anti-SSA/Ro assays and were considered to be reactive only with Ro52 and not with Ro60. This anti-Ro52 reactivity was confirmed by natural and recombinant Ro52 in 16/18 cases. 12/18 sera corresponded to connective tissue diseases. CONCLUSION: Anti-Ro52 positive sera without any evidence of anti-Ro60 and anti-La/SSB reactivity can be considered as an independent group that is systematically missed by classical anti-SSA/Ro detection methods owing to a bias towards anti-Ro60 reactivity. The anti-Ro52 sera are precipitin negative, not retrieved by SSA/Ro enzyme linked immunosorbent assays (ELISAs) based on natural SSA/Ro, and show no specific ANA fluorescence staining pattern. These findings together with the clinical data indicate that anti-Ro52 should be considered as an additional and independent serum marker.

Antibodies, Antinuclear↗
PubMed1994

Production and characterization of monoclonal antibodies directed against high and low molecular weight kininogens.

HMWK and LMWK were purified from human plasma by ion exchange and affinity chromatography and used to raise anti-kininogen monoclonal antibodies. The Ig class and affinity of these Mab's that are directed at the heavy chain of the kininogens, were determined. Plasma samples of two patients, one with acquired C1-inhibitor deficiency and angioedema and one with idiopathic angioedema were analized by immunoblotting with these Mab's. Both were found to have cleaved HMWK during clinical attacks.

Angioedema↗
PubMed1989

Long-term cultivation of cryopreserved human fetal brain cells in a chemically defined medium.

Conditions for long-term cultivation of human fetal brain cells in a chemically defined medium were established using cryopreserved brain fragments obtained from legal abortions. Tissue of the same gestational age was pooled and the cells cultured in a fully defined medium containing insulin-like growth factors (IGF I and II). Primary cultures were kept for 2-4 weeks and secondary or tertiary cultures could be maintained for 3 months. The cultures were characterized by morphological, electrophysiological and biochemical methods. Glial cells were predominant during the first two weeks of culture. In later stages of cultivation, glial cells diminished in number and most cells were neuronal. Voltage-dependent Na+ channels were recorded from neurons. Biochemical studies indicated that the fetal brain cells contained and secreted immunoreactive somatostatin as well as the tachykinins, substance P and neurokinin A. Cultures grown in IGF II- or nerve growth factor-containing medium expressed increased choline acetyltransferase activity.

Brain↗
PubMed1986

Acquired C1 esterase-inhibitor deficiency: case report with emphasis on complement and kallikrein activation during two patterns of clinical manifestations.

A case of severe angioedema with several episodes of life-threatening attacks during a follow-up of 7 years is presented. Although the biologic profile is that of an acquired C1 INH deficiency, no lymphoproliferative malignancy or immune-complex disease could be proven until now. However, the patient has had a small monoclonal IgG lambda-gammopathy for 4 years. During the last 4 years, edematous manifestations have stopped. The patient now suffers at regular intervals of about a week from short-lasting attacks with digestive and vasomotor symptoms. This clinical evolution is accompanied by a worsening in the complement abnormalities. The digestive and vasomotor attacks were found to be correlated with sudden prekallikrein and high-molecular-weight kininogen consumption. These findings demonstrate that prekallikrein is activated during acquired C1 INH deficiency and that the products of this pathway such as bradykinin are probably responsible for a part of the clinical manifestations associated with this disorder.

Aged↗
PubMed1984

Insulinlike growth factors bind to specific receptors in isolated pancreatic acini.

Recently we have demonstrated the existence of specific receptors for insulin on pancreatic acini. Employing 125I-labeled insulinlike growth factors (IGFs) and insulin, we report the existence of distinct receptors for IGF-I and IGF-II on mouse pancreatic acini. Insulin competes with 125I-IGF-I with 1,000-fold less potency. By contrast, insulin increases the binding of 125I-IGF-II to its receptor. IGF in turn inhibits 125I-insulin binding to its receptor but with 250-fold less potency. Thus, distinct receptors exist on acini for IGF-I, IGF-II, and insulin. Moreover, IGF, like insulin, stimulates sugar transport by acini. The mechanism of IGF stimulation may be similar to insulin, as the effect of maximal concentrations of the two peptides when added together is not additive. These results raise the possibility, therefore, that IGFs may be a new class of physiological regulators of pancreatic acinar cell function.

Animals↗
PubMed1984

Insulin-like growth factor I/somatomedin C (IGF-I/Sm C): comparison of natural, solid phase synthetic and recombinant DNA analog peptides in two radioligand assays.

Investigation of the biologic activity of Insulin-like Growth Factor I/Somatomedin C (IGF-I/Sm C) has been hampered by the scarcity of purified material. The synthesis of this molecule by the solid phase procedure and an analog of IGF-I/Sm C by recombinant DNA technology offers promise that studies of the biologic activity of IGF-I/Sm C will soon be possible. We have found that natural IGF-I/Sm C and the two synthetic peptides behave similarly in two radioligand systems, providing evidence that these molecules possess the requisite structural integrity for use in such biological studies.

Humans↗
PubMed1982

Evidence for the presence of specific receptors for insulin-like growth factors 1 (IGE-1) and 2 (IGF-2) and insulin throughout the adult human brain.

The present study examines adult human brain tissue for the presence of receptors for insulin-like growth factors (IGFs) 1 and 2 and insulin. Binding sites for all hormones were widely distributed throughout the brain removed at autopsy, with the highest specific binding being found in the various cortical regions. Cross-reaction studies performed on frontal lobe biopsy material indicated specific binding sites for IGF-1 and insulin whereas iodinated IGF-2 was equally displaced by IGF-1 and IGF-2, suggesting the presence of an additional IGF-2-like binding site in the adult brain.

Aged↗
PubMed1982

[Somatomedin inhibition of the growth hormone secretion stimulated by the hypothalamic factor somatocrinin or the synthetic peptide hpGRF].

In the in vitro monolayer pituitary cell culture system somatomedin-C and IGF-I are practically equipotent to inhibit the secretion of growth hormone stimulated by hypothalamic growth hormone releasing factor (GRF) or the synthetic peptide hpGRF-44 (3-200 x 10(-12)M). Highly purified somatomedin-C or IGF-I are active to inhibit the effect of GRF at concentrations of 0.5 to 10 ng/ml(1.0 x 10(-10) M - 1.3 x 10(-9) M) in either short-term (3-4 hrs.) or long-term (24 hrs.) incubation, with no statistical difference between the results obtained in either duration of incubation. IGF-II is less potent than IGF-I as an inhibitor of GRF. The effect of the somatomedins is specific for the secretion of growth hormone and is not duplicated by other growth factors such as epidermal growth factor (EGF) or fibroblast growth factor (FGF).

Animals↗
PubMed1982

[Role of the thickness of the graft in osteocartilaginous autotransplantation in the rabbit knee].

This experimental study is complementary to the clinical series of cartilaginous autografts in the knee for medial condylar necrosis. The aim was to determine the viability of the articular cartilage in a series of grafts with variable thickness of the underlying spongy bone. The study was done on 36 adult rabbits and the cartilage was studied by biochemical, histochemical and ultrastructural methods. The results are conclusive. The earliest abnormal signs in the first few weeks affect the thinnest grafts of 4 mm whereas the 12 mm thickness grafts hardly show any lesions. It is therefore possible to use large autogenic grafts for osteocartilaginous defects provided the proportion between the area of the articular surface and the underlying spongy bone of the graft is at least 1/4. Under these circumstances, cartilaginous deterioration will be avoided and reduce long term degeneration.

Animals↗