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Biomedical subjects

E Lindh

Publications and source records attributed to E Lindh.

51 records · Page 3Linked to original sources
PubMed1988

Kinetic evidence for cytoplasmic calcium as an inhibitory messenger in parathyroid hormone release.

A sudden change of extracellular Ca2+ from 0.5 to 3.0 mM resulted in a transient rise of the cytoplasmic Ca2+ concentration (Ca2+i) followed by a sustained increase in parathyroid cells loaded with the Ca2+-indicator fura-2. The initial transient could be eliminated by increasing the Ca2+ buffering capacity of the cytoplasm. Under such conditions the rise of Ca2+i exhibited kinetics reminiscent of those for 45Ca uptake and cell depolarization. Addition of 0.5 mM Mn2+ mimicked the effect of raising the extracellular Ca2+ concentration, since there was an initial Ca2+i transient followed by a slower entry of Mn2+ into the cells. This reaction pattern was different from that of pancreatic alpha 2-cells in which there was no substantial influx of Mn2+ before depolarization with arginine. When measuring the kinetics of parathyroid hormone (PTH) release it was apparent that Ca2+ inhibition of secretion followed Ca2+i and thus became substantially delayed after eliminating the initial transient. The results support the concept of a depolarizing Ca2+ permeability in the parathyroid cell membrane which can be activated by external Ca2+, and indicate that Ca2+i is an inhibitory messenger of importance for the physiological regulation of PTH release.

Animals↗
PubMed1988

Dimethyl sulfoxide inhibits proliferation but not hypertrophy and functional dedifferentiation of bovine parathyroid cells in culture.

Primary cultures of bovine parathyroid cells were used to study the relationship between parathyroid hormone (PTH) release, regulation of the cytoplasmic Ca2+ concentration (Ca2+i) and cell growth. Parathyroid cells were seeded into fibronectin-coated culture wells in the absence (control) or presence of 2% (v/v) dimethyl sulfoxide (DMSO). Both groups of cells attached and flattened out, and during 4 days of culture the cell diameters and protein content increased. However, whereas the number of cells in the control group increased by 60% and their 3H-thymidine incorporation tenfold, the DMSO cultured cells exhibited no signs of cell proliferation. Despite this difference in cell replication rate both groups of cells developed similar functional dedifferentiation. There was consequently a decreased Ca2+ suppressibility of PTH release, and Ca2+i did not follow the ambient Ca2+ concentration in a usual manner. It is concluded that during culture bovine parathyroid cells develop morphological and functional abnormalities similar those in parathyroid cells from patients with hyperparathyroidism. Moreover, this functional dedifferentiation could be dissociated from increased cell proliferation but may be related to cell hypertrophy.

Animals↗
PubMed1987

Treatment of hormone-producing adrenocortical cancer with o,p'DDD and streptozocin.

Three patients with advanced adrenocortical carcinoma were treated with a combination of intermittent streptozocin and continuous o,p'DDD. Two patients were treated preoperatively and the primary tumors, initially considered as inoperable, could be resected after 19 and 5.5 months, respectively. In the patient with the longer treatment (35 months), lung and lymph node metastases disappeared and she has no evidence of recurrent disease 6.5 years after start of therapy. One patient was followed by magnetic resonance imaging (MRI) and urinary steroid secretion. The MRI gave a good visualization of the tumor. Measurements of relaxation times showed a significant decrease in T1 values. The urinary steroid profile showed an increased secretion of 3 beta-hydroxy-5-ene steroids and tetrahydro-11-deoxy-cortisol. Treatment with streptozocin and o,p'DDD initially increased 16-oxygenation of dehydroepiandrosterone and androst-5-en-3 beta,17 beta-diol, followed by a decrease in the secretion of all urinary steroids. The third patient received postoperative treatment with no effect on metastatic disease in the lungs, she died 9 months after start of treatment. The therapeutic approach with the combination regimen of streptozocin and o,p'DDD pretreatment plus aggressive surgery has to be further evaluated, as well as MRI and urinary steroid profile as methods to monitor the effect of therapy.

Adrenal Cortex↗
PubMed1987

Bimodal regulation of secretion by cytoplasmic Ca2+ as demonstrated by the parathyroid.

Bovine parathyroid cells were used to study parathyroid hormone (PTH) release and the cytoplasmic Ca2+ concentration (Cai2+). When the extracellular Ca2+ concentration was decreased from 3.0 to 0.5 mM, perifused cells reacted with rapid stimulation of PTH release. However, a further reduction of extracellular Ca2+ to less than 10 nM resulted in prompt inhibition. Both effects were readily reversible. Using the intracellular Ca2+ indicator quin-2 also as a buffer for calcium it was possible to control Cai2+ within the 20-600 nM range. PTH release was found to increase with Cai2+ up to 200 nM but was gradually suppressed above this concentration.

Aminoquinolines↗
PubMed1987

Cytoplasmic Ca2+ concentration of single normal human and bovine parathyroid cells measured by dual wavelength microfluorometry.

Dual wavelength microfluorometry was utilized to measure the cytoplasmic calcium concentration (Cai2+) of single parathyroid cells loaded with the indicator fura-2. The method enabled the first registrations of Cai2+ of normal human parathyroid cells, available only in minute numbers. At 0.5 mM extracellular Ca2+, the Cai2+ levels were similar in normal human and bovine cells. Both cell types responded with an initial Cai2+ transient followed by a sustained increase when raising extracellular Ca2+ to 3.0 mM. The sustained effect exhibited a sigmoidal relation to extracellular Ca2+ in the 0.5-3.0 mM range. Although the increase was somewhat greater in the human cells, the half maximal responses were obtained at almost identical extracellular Ca2+ concentrations. Whereas K+ depolarization decreased Cai2+, the Ca2+ channel blocker D-600 had dual actions, raising Cai2+ at 0.5 mM Ca2+ and decreasing it at 3.0 mM Ca2+, and the effects were similar in the bovine and human cells. The present experimental approach verified the validity of utilizing bovine cells as controls in studies of human parathyroid tissue and it appears suitable for analysis of the role of different subpopulations of parathyroid cells in the abnormal parathyroid tissue of patients with hyperparathyroidism.

Animals↗
PubMed1987

Development of abnormal parathyroid cell function during monolayer culture and its relation to cellular hypertrophy and proliferation.

Primary cultures of adult bovine parathyroid cells grown for up to 8 days were used to study the relationship between regulation of parathyroid hormone (PTH) release, cytoplasmic Ca2+ (Ca2+i) and cell growth. Cell counting indicated that proliferation was inversely proportional to the seeding density. The culture was associated with cell enlargement without apparent relation to the proliferation rate. Moreover, flow cytometric analysis of the DNA distribution excluded that the hypertrophy was due to a high proportion of the cells being in the S and G2 stages of the cell cycle. With progressive time in culture there was a gradual deterioration of the ability of increasing concentrations of extracellular Ca2+ to suppress PTH secretion and raise Ca2+i. This functional dedifferentiation developed to the same extent despite considerable differences in proliferation rates. The data show that parathyroid cells in monolayer culture develop functional and some of the morphological characteristics of parathyroid cells from patients with hyperparathyroidism and that the functional abnormality seems to be related to hypertrophy but not to proliferation of the cells.

Animals↗
PubMed1977

A rapid, semi-automated counting procedure for enumeration of antibody-forming cells in gel and nucleated cells in suspension.

A commercially available bacterial colony counter has been modified to permit rapid, highly accurate, semi-automated enumeration of antibody-producing plaque forming cells in semi-solid support medium as well as enumeration of nucleated cells in suspension on a standard hemacytometer chamber. This apparatus should therefore serve as an enormous time-conserving accessory to most modern laboratories involved in immunological research.

Animals↗
PubMed1977

The finding that secretory component is not associated with gamma-glutamyltranspeptidase activity.

The gamma-glutamyltranspeptidase activity of human milk was concentrated by ammonium sulphate precipitation. On gel chromatography of the dissolved precipitate, the activity was eluted in the high-molecular-weight fraction containing secretory IgA, while no activity appeared in the eluate at the position of free secretory component. Various antisera were added to portions of the pool of active fractions. No change of gamma-glutamyltranspeptidase activity appearedse activity was obtained with antisera against either IgA, secretory IgA or secretory component, while a large reduction of activity was seen with anti-human colostrum. Finally, purified free secretory component, secretory IgA and in vitro complexes between secretory component and IgA dimers were shown to be inactive in the gamma-glutamltranspeptidase assay, both in the absence and presence of zinc ions. Thus secretory component, either when free or bound to IgA, does not exhibit gamma-glutamyltranspeptidase activity, and therefore cannot function as such an enzyme in the transport of IgA across mucous membranes, as has been suggested previously.

Animals↗
PubMed1977

Relative rates of the non-covalent and covalent binding of secretory component to an IgA dimer.

The rate of binding of free secretory component to an IgA dimer in vitro was studied by high-voltage gel electrophoresis at different times after mixing. The rate of the formation of the covalent component of the interaction (i.e. the disulphide interchange reaction) was monitored separately by denaturing the proteins in 6 M guanidine hydrochloride at different times after mixing and subsequently estimating the amount of covalently bound secretory componenet by gel chromatography in the denaturing solvent. The rates of the two reactions could not be distinguished in experiments at 37 degrees or 20 degrees C. At 4 degrees C, however, secretory component bound to the IgA dimer almost as rapidly as at higher temperatures, while the rate of the disulphide interchange was considerably lower. This indicates that the noncovalent interactions are the primary type of bonds formed between secretory component and IgA, and that the formation of these bonds initiate the disulphide interchange reaction, the rate of which is highly dependent on temperature.

Binding Sites, Antibody↗
PubMed1976

Binding of secretory component to dimers of immunoglobulin A in vitro. Mechanism of the covalent bond formation.

A complex between secretory component and an immunoglobulin A (IgA) myeloma dimer has been studied in vitro as a model to elucidate the mechanism of the formation of disulfide bonds during assembly in vivo of secretory immunoglobin A. A small amount of free thiol groups, totally about 0.4 groups per mole of protein, were shown to be present on both the heavy and light chains of the IgA dimer, but not on its J-chain, while no such groups could be demonstrated on free secretory component. The SH-groups on IgA most likely exist as a result of incomplete oxidation of some intra-or interchain disulfide bonds of the molecule, analogous to what has been suggested for IgG. Several types of evidence indicated that the disulfide bonds between secretory component and IgA are formed after the noncovalent association of the two proteins by a sulfhydryl group-disulfide bond exchange reaction, in which the small amount of free sulfhydryl groups on the IgA dimer initiate the reaction by reducing a reactive disulfide bond on secretory component. This exchange reaction, which thus proceeds by the mechanism of so-called disulfide interchange reactions, requires certain conformational features of one or both of the proteins and leads to the formation of presumably two new interchain disulfide bonds between secretory component and IgA. The reaction does not progress to completion, however, but ends in an equilibrium so that a small proportion of the secretory component molecules always are unattached by disulfide bonds.

Binding Sites↗
PubMed1976

Binding of secretory component to human immunoglobulin M.

The binding of human free secretory component to immoglobulin M (IgM) has been studied in vitro as a model for the formation of complexes between the two proteins in vivo. Three IgM myelomas and normal serum IgM were found to bind secretory component in amounts from 0.8 to 2.0 mol per mol of IgM. This variation in binding was not related to a corresponding variation of the J-chain content of the immunoglobulins, but more likely it was due to varying amounts of unspecifically bound serum proteins blocking the attachment of secretory component. In contrast to complexes with immunoglobulin A (IgA), the binding of secretory component to IgM appeared to be solely of a noncovalent nature, as all secretory component was released from complexes with IgM during gel chromatography in 6 M guanidine hydrochloride. Studies with tryptic fragments of one of the IgM myelomas indicated that the binding site for secretory component is located on the (Fc)5mu part of the IgM pentamer. Finally, only minimal conformational changes were found to accompany complex formation between secretory component and IgM, analogous to what has earlier been reported for the attachment of the secretory component to IgA.

Binding Sites↗
PubMed1975

Increased risistance of immunoglobulin A dimers to proteolytic degradation after binding of secretory component.

The contribution of secretory component to the stability of secretory IgA against proteolysis has been studied by a new approach, i.e., by comparing the proteolytic degradation of the complexes formed in vitro between these proteins and secretory component. The results show that attachment of secretory components to the dimeric backbone of the secretory IgA molecule is accompanied by a significantly increased resistance of this backbone against digestion by both trypsin and pepsin. This protective effect may be a physiologic function of secretory component or may be due merely to unspecific blocking by secretory component of one or more sensitive peptide bonds in the IgA backbone.

Absorption↗
PubMedDate not supplied

Effect of interferon on T1 relaxation times of liver metastases from endocrine gastrointestinal tumours.

Eight patients with liver metastases from endocrine gastrointestinal tumours were examined with magnetic resonance imaging of the liver before and during treatment with interferon. T1, T2 and tumour size were measured and compared with tumour marker levels and symptomatic improvement or deterioration. Before therapy all tumours showed a long T1 and T2, in comparison to normal liver and fat, and during therapy they all showed a decrease in T1. As no change in liver T1 and fat T1 occurred, the decreased tumour T1 is considered to be a therapy effect. This cannot be fully explained but is possibly due to a reduction in tumour growth rate during interferon treatment. There was no certain correlation between tumour T1 and tumour marker levels or symptomatic changes.

Carcinoid Tumor↗