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Biomedical subjects

C Larsson

Publications and source records attributed to C Larsson.

At least 325 records · Page 18Linked to original sources

Effect of detergents on the H(+)-ATPase activity of inside-out and right-side-out plant plasma membrane vesicles.

In search for a detergent to be used to assess the sidedness of plant plasma membrane vesicles by enzyme latency we tested the effect of 42 detergents on the ATPase activity of right-side-out and inside-out plasma membrane vesicles from sugar beet leaves. Most of the detergents seemed to inactivate the ATPase in addition to disrupting the permeability barrier to ATP. There were two main exceptions, namely long chain polyoxyethylene acyl ethers, such as detergents of the Brij series and Lubrol WX, and long chain lysophospholipids. These two types of detergents permeabilized the membranes at low concentrations and did not inhibit the ATPase at higher concentrations. Unmasking of latent active sites seemed to explain the activation of the plasma membrane H(+)-ATPase produced by long chain polyoxyethylene acyl ethers. These detergents should therefore be ideal for determination of vesicle orientation based on ATPase latency. By contrast, long chain lysophospholipids were found to be highly specific activators of the enzyme. In addition, long chain fatty acids were found to strongly inhibit ATP-dependent proton accumulation in the vesicles without inhibiting ATP hydrolysis. This uncoupling effect of the fatty acids could be abolished by the addition of fatty acid-free bovine serum albumin (BSA). Similarly, the proton transport capacity of ageing vesicles could be restored by addition of BSA. The latter findings may explain why isolated plasma membranes so often exhibit increased permeability to protons on ageing.

Cell Membrane↗

Genomic alterations in human breast carcinomas.

All human chromosomes were screened in 52 human breast carcinomas for the occurrence of allele losses, in order to identify genomic alterations involved in initiation and progression of the disease. Loss of chromosome 22 alleles was detected in 6 out of 8 lobular carcinomas, while chromosome 17 losses were most frequent in ductal carcinomas. Furthermore, patients who developed advanced disease after many years of mild clinical course showed significantly higher frequencies of allele losses in their primary tumors, compared to patients with a persistently mild disease course. Finally, in one case, molecular examination suggested a translocation t(10;17) with coamplification of the ERBB2 oncogene and chromosome 10 sequences present in the two tumors from this patient, consistent with one of the tumors being a metastasis originating from a subclone of cells in the other tumor.

Adenocarcinoma, Mucinous↗

Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors.

The gene for multiple endocrine neoplasia type 1 (MEN1), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, we could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas.

Adenoma↗

Sealed inside-out and right-side-out plasma membrane vesicles : optimal conditions for formation and separation.

Plasma membrane preparations of high purity (about 95%) are easily obtained by partitioning in aqueous polymer two-phase systems. These preparations, however, mainly contain sealed right-side-out (apoplastic side out) vesicles. Part of these vesicles have been turned inside-out by freezing and thawing, and sealed inside-out and right-side-out vesicles subsequently separated by repeating the phase partition step. Increasing the KCI concentration in the freeze/thaw medium as well as increasing the number of freeze/thaw cycles significantly increased the yield of inside-out vesicles. At optimal conditions, 15 to 25% of total plasma membrane protein was recovered as inside-out vesicles, corresponding to 5 to 10 milligrams of protein from 500 grams of sugar beet (Beta vulgaris L.) leaves. Based on enzyme latency, trypsin inhibition of NADH-cytochrome c reductase, and H(+) pumping capacity, a cross-contamination of about 20% between the two fractions of oppositely oriented vesicles was estimated. Thus, preparations containing about 80% inside-out and 80% right-side-out vesicles, respectively, were obtained. ATPase activity and H(+) pumping were both completely inhibited by vanadate (K(i) approximately 10 micromolar), indicating that the fractions were completely free from nonplasma membrane ATPases. Furthermore, the polypeptide patterns of the two fractions were close to identical, which shows that the vesicles differed in sidedness only. Thus, preparations of both inside-out and right-side-out plasma membrane vesicles are now available. This permits studies on transport, signal transduction mechanisms, enzyme topology, etc., using plasma membrane vesicles of either orientation.

Journal Article↗

Osmoregulation of the salt-tolerant yeast Debaryomyces hansenii grown in a chemostat at different salinities.

The intracellular solute composition of the salt-tolerant yeast Debaryomyces hansenii was studied in glucose-limited chemostat cultures at different concentrations of NaCl (4 mM, 0.68 M, and 1.35 M). A strong positive correlation between the total intracellular polyol concentration (glycerol and arabinitol) and medium salinity was demonstrated. The intracellular polyol concentration was sufficient to balance about 75% of the osmotic pressure of the medium in cultures with 0.68 and 1.35 M NaCl. The intracellular concentration of K+ and Na+, which at low external salinity gave a considerable contribution to the intracellular water potential, was only slightly enhanced with raised medium salinity. However, the ratio of intracellular K+ to Na+ decreased; but this decrease was less drastic in the cells than in the surrounding medium, i.e., the cells were able to select for K+ in favor of Na+. The turgor pressure, which was estimated on the basis of intracellular solute concentrations, was 2,200 kPa in cultures with 4 mM NaCl and decreased when the external salinity was raised, resulting in a value of about 500 kPa in cultures with 1.35 M NaCl. The maintenance of a positive turgor pressure at high salinity was mainly due to an increased production and accumulation of glycerol.

Glucose↗

Diurnal variation of carbamazepine and carbamazepine-10,11-epoxide in plasma and saliva in children with epilepsy: a comparison between conventional and slow-release formulations.

In order to overcome the problems of interdosage fluctuations of body fluid concentrations of carbamazepine, a slow-release formulation has been developed. In an open, controlled, within-patient study, the diurnal plasma concentrations of carbamazepine and its 10,11-epoxide were measured in 25 epileptic children first treated with conventional carbamazepine tablets (Tegretol) and then with the Tegretol slow-release preparation. The diurnal plasma concentration curves during treatment with the slow-release formulation showed significantly less variation over 24 hours than during treatment with the ordinary preparation, as measured by the fluctuation index. Mean concentration values also differed significantly, which is explained by a somewhat reduced bioavailability (22% less) of the slow-release formulation. There were no differences in efficacy and tolerability between the two formulations, but there was a clear-cut reduction of reported side effects, especially tiredness, on treatment with the slow-release formulation. For that reason, the slow-release formulation should be a major advantage in treating children with epilepsy, in order to avoid interference with cognitive functions. In 12 children, simultaneous measurements of the concentration of carbamazepine and its epoxide in saliva were made and compared with the plasma values. As expected, the concentration curves corresponded, indicating that saliva sampling is an appropriate alternative for monitoring the concentration of carbamazepine. All children remained on the slow-release preparation after the trial and were followed up for 12 months or more.

Adolescent↗

Multiple endocrine neoplasia.

The recent chromosomal mapping of the genes for two different autosomal dominant inherited predispositions to multiple endocrine neoplasias promises to be a significant breakthrough for the understanding of the pathogenesis of such lesions. Multiple endocrine neoplasia type 1 (MEN1) associates primary hyperparathyroidism, lesions of the endocrine pancreas and pituitary adenomas. The first hint that the MEN1 gene is localized on chromosome 11 came from the finding of allele losses in MEN1 associated tumours. Subsequent genetic linkage analysis to restriction fragment length polymorphism (RFLP) markers assigned the gene to chromosome band 11q13. MEN2A is characterized by medullary thyroid carcinoma and phaeochromocytoma. The disease locus was localized to the centromeric region of chromosome 10 by genetic linkage. For both syndromes genetic linkage maps of the flanking regions have been established, and a set of RFLP markers is now available for premorbid identification of gene carriers in affected families. Analysis of allele losses showed that tumorigenesis of parathyroid and pancreatic lesions results from unmasking of a recessive mutation at the MEN1 locus, and by deletion mapping the tentative MEN1 region was restricted to a few million base pairs. In contrast, such losses appear to be relatively rare in MEN2A associated lesions.

Adrenal Gland Neoplasms↗

Verbal memory function after subarachnoid haemorrhage determined by the localisation of the ruptured aneurysm.

A total of 219 patients who had suffered from subarachnoid haemorrhage (SAH) were given a set of memory tests. The tests comprised immediate free recall (indexing long-term memory, LTM, and short-term memory, STM), final free recall (LTM) and final cued recall (LTM) of words as well as a digit-span test (an index of working memory, WM). STM was highly sensitive to brain damage caused by SAH whereas WM was not. Localisation of the ruptured aneurysm, angiographic vasospasm or mass effect did not have any selective influence on the SAH group's STM or WM. The final free recall test was the most sensitive measure of LTM whereas the LTM part of the immediate free recall test was the least sensitive. LTM impairment was most pronounced for patients with ruptured left anterior communicating artery aneurysms or for patients with angiographic vasospasm or mass effect. It is suggested that, in the SAH patients, a passive phonological short-term store is impaired, but the active maintenance rehearsal mechanism is intact. For patients with LTM dysfunction, deeper, more elaborate, active processing is disrupted, hindering efficient long-term storage.

Adult↗

Localization of the genetic defect in multiple endocrine neoplasia type 1 within a small region of chromosome 11.

Multiple endocrine neoplasia type I (MEN-1), a Mendelian disorder with an autosomal dominant mode of inheritance, causes hyperplasia in the parathyroid glands and hyperplasia or neoplasm in the anterior pituitary gland and/or the pancreatic islets. The genetic defect responsible for MEN-1 in three families was recently mapped to the long arm of chromosome II by linkage between the MEN-1 locus and the gene for skeletal muscle glycogen phosphorylase (PYGM) at 11q13. We have constructed a genetic linkage map of seven markers in the vicinity of the MEN-1 locus that has allowed us to map more precisely the gene associated with MEN-1; the target region has been narrowed to about 12 cM. The closely linked markers will be useful also for identification of likely carriers in families in which an allele responsible for MEN-1 segregates.

Chromosome Mapping↗

Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma.

Multiple endocrine neoplasia type 1 (MEN-1) is a predisposition to hyperplasia of the parathyroid glands, and to hyperplasia or tumours of the anterior pituitary and the endocrine pancreas, and is inherited as an autosomal dominant trait. Here we map the MEN-1 locus to chromosome 11 by family studies, and demonstrate tight linkage with the human muscle phosphorylase gene. By comparing constitutional and tumour tissue genotypes of insulinomas from a pair of brothers who had inherited MEN-1 from their mother, we have shown that oncogenesis in these cases involves unmasking of a recessive mutation at this locus.

Adenoma, Islet Cell↗

Microcalorimetric monitoring of growth of Saccharomyces cerevisiae: osmotolerance in relation to physiological state.

The importance of the physiological state of a culture of Saccharomyces cerevisiae for tolerance to sudden osmotic dehydration was studied, and it was investigated whether specific osmotolerance factors were demonstrable. The microcalorimeter was used to monitor growth, and different physiological states of the culture were selected and their osmotolerance was tested. In addition to cells in the stationary phase, cells from the transition phase between respirofermentative and respiratory catabolism were osmotolerant. S. cerevisiae exhibited ever-changing metabolism during batch growth on either glucose or ethanol as the carbon source. Instantaneous heat production per biomass formation (dQ/dX) and specific activity of sn-glycerol 3-phosphate dehydrogenase (GPDH) (EC 1.1.1.8) were shown to differ for different physiological states. Neither high respiratory activity nor low total cellular activity, nor factors involved in osmoregulation, i.e., intracellular glycerol or activity of GPDH, correlated with the osmotolerant phenotype.

Adaptation, Physiological↗

No difference in general well-being during antihypertensive treatment with atenolol or metoprolol CR.

Atenolol and metoprolol are the two most widely used beta 1-adrenoceptor antagonists in the treatment of essential hypertension. Differences in their physico-chemical properties have been the basis of a number of clinical studies whose primary or secondary objective has been to compare subjective well-being during treatment with these beta-selective blockers. The results are, however, contradictory, mainly due to factors such as open study design, different dose regimens and dissimilar study populations. The aim of the present study was to evaluate and compare subjective well-being during treatment with atenolol (50 mg o.d.) and metoprolol CR (100 mg o.d.) in a randomized double-blind, cross-over study (2 x 6 weeks) in hypertensives not previously treated with either of the drugs studied. Two self-administered questionnaires (MSE-profile and Jern quality of life questionnaire) were filled in both before randomization and before follow up visits at 1, 3 and 6 weeks in each treatment period. Furthermore, subjective symptoms, blood pressure and heart rate were monitored. At the end of the study, patients were requested to state what treatment they preferred. Atenolol and metoprolol CR were found to be equally effective in reducing blood pressure (from 159/98 to 144/87 and 144/88 mm Hg, respectively, n = 74). The MSE-profile and the Jern quality of life questionnaire could not detect any differences between the two treatments as regards general well-being. Other subjective symptoms (e.g. diarrhoea, bradycardia, cold hands and feet) were uncommon and equally distributed among atenolol and metoprolol patients. 31 of the patients preferred metoprolol CR, 23 atenolol, while 20 had no preference.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol↗

Glycerol production in relation to the ATP pool and heat production rate of the yeasts Debaryomyces hansenii and Saccharomyces cerevisiae during salt stress.

Changes in glycerol production and two parameters related to energy metabolism i.e. the heat production rate and the ATP pool, were assayed during growth of Saccharomyces cerevisiae and Debaryomyces hansenii in 4 mM and 1.35 M NaCl media. For both of the yeasts, the specific ATP pool changed during the growth cycle and reached maximum values around 10 nmol per mg dry weight in both types of media. The levels of glycerol were markedly enhanced by high salinity. In the presence of 1.35 M NaCl, D. hansenii retained most of its glycerol produced intracellularly, while S. cerevisiae extruded most of the glycerol to the environment. The intracellular glycerol level of S. cerevisiae equalled or exceeded that of D. hansenii, however, with values never lower than 3 mumol per mg dry weight at all phases of growth. When D. hansenii was grown at this high salinity the intracellular level of glycerol was found to correlate with the specific heat production rate. No such correlation was found for S. cerevisiae. We concluded that during salt stress, D. hansenii possesses the capacity to regulate the metabolism of glycerol to optimize growth, while S. cerevisiae may not be able to regulate when exposed to different demands on the glycerol metabolism.

Adenosine Triphosphate↗

In vitro binding of 3H-acetylcholine to nicotinic receptors in rodent and human brain.

The binding of 3H-acetylcholine (3H-ACh) to nicotinic receptors in rodent and human brain was measured in the presence of atropine to prevent binding to muscarinic binding sites. 3H-ACh binds specifically and saturably to rodent brain. From saturation binding Kd was 30 nM in rat cerebral cortex, which is close to that calculated from kinetic experiments. The binding was temperature-dependent, being highest at low temperatures and decreasing at higher temperatures. The regional distribution of binding in mouse brain was not uniform. The binding was highest in the midbrain, intermediate in the cerebral cortex and striatum, and lowest in the cerebellum, hippocampus, hypothalamus and medulla oblongata. No significant correlation was found between the regional 3H-ACh binding and the regional binding of 3H-alpha-bungarotoxin (3H-BTX), 3H-nicotine (3H-NIC), 3H-tubocurarine and the endogenous acetylcholine content, although the correlation value for 3H-ACh/3H-NIC was at the limit for significance. 3H-ACh also bound specifically to human cerebral cortical tissue and this binding was approximately three times lower than in rodent brain, when a low 3H-ACh concentration was used. In contrast to rat brain there appears to exist multiple binding sites for 3H-ACh in human cerebral cortex as suggested by the curvelinear nature of the Scatchard plot. It was calculated that 3H-ACh bound with Kd 4 nM and Bmax 8 pmol/g protein and Kd 112 nM and Bmax 67 pmol/g protein. The Hill number of 1.5 for the binding of low concentration and 2.5 for high concentration of 3H-ACh also suggest that the 3H-ACh-binding sites interaction exhibit positive cooperativity.

Acetylcholine↗

Lipid composition of plasma membranes isolated from light-grown barley (Hordeum vulgare) leaves: identification of cerebroside as a major component.

The total lipid composition of highly purified plasma membranes from light-grown barley (Hordeum vulgare) leaves was investigated. The plasma membranes were separated from intracellular membranes by subfractionation of the microsomal fraction using aqueous polymer two-phase partitioning. A novel finding was that glucocerebroside was a major lipid of the plasma membrane (23 mol%). The most abundant lipid class in the plasma membrane was phospholipid (42 mol%), consisting mainly of phosphatidylcholine and phosphatidylethanolamine, together with free sterols at a level of 28 mol%. The only free sterols of the plasma membrane were campesterol (15%), stigmasterol (23%), and sitosterol (62%). The plasma membrane contained a relatively high proportion of saturated fatty acids compared to the bulk of intracellular membranes, the major components of the plasma membrane being palmitic (16:0), linoleic (18:2), and linolenic (18:3) acids in approximately equal amounts.

Cell Membrane↗