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Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 451 records · Page 25Linked to original sources

Vasopressin release in response to intracerebroventricular L-alanine and L-arginine, and its dependence upon CSF NaCl concentration.

Influences on renal water, electrolyte, and arginine vasopressin (AVP) excretions of 1 h infusions (20 microliters/min) of a neutral (L-alanine) and two basic (L-lysine and L-arginine) amino acids into the lateral cerebral ventricle were studied in hydrated goats, and were compared to effects of control infusions of hypertonic (0.25 M) NaCl. L-alanine (0.11 M) dissolved in hypotonic NaCl caused more pronounced inhibition of the water diuresis and greater increase in AVP excretion than did the control infusions, but, in comparison to the latter, the responses developed very slowly. The effects were further delayed and were much attenuated when L-alanine was administered in isotonic glucose, but became considerably accentuated when isotonic NaCl was used as the solvent. L-lysine (0.09 M) in hypotonic NaCl did not inhibit the water diuresis or cause any apparent AVP release, whereas the corresponding L-arginine infusions caused inhibition of the water diuresis and increase in AVP excretion of approximately the same magnitudes and time courses as the control infusions. Like for L-alanine, these effects became accentuated when L-arginine was dissolved in isotonic NaCl, and became delayed and much attenuated when isotonic glucose was used as the solvent. L-arginine induced a more pronounced increase in renal Na excretion than did L-alanine and 0.25 M NaCl. Since transport together with Na (increasing the Na influx) generally is much more important for cellular uptake of neutral than of basic amino acids, the possibility is discussed that L-alanine here might have caused AVP release by increasing transmembrane Na transport of juxtacerebroventricular Na sensors regulating the AVP secretion--a suggestion supported by the lack of response to the basic L-lysine. The antidiuretic effect of the other basic amino acid, L-arginine, can not be explained along this line. However, with regard to the characteristic differences observed between the responses to L-alanine and L-arginine, the possibility is discussed that the latter might not have acted at a sensory level, but on the final neuronal link in the release of neurohypophyseal hormones, the hypothalamic neurosecretory cells. In contrast to L-alanine and L-arginine, L-lysine appeared to stimulate the appetite of the goats.

Alanine↗

Fasting serum bile acids in liver disease. A comparison with histological features.

In a prospective series of 205 patients undergoing liver biopsy, fasting plasma total bile acid (TBA) levels were compared with 11 different histological features. The TBA level was found to correlate positively (P less than 0.001) with the extent of total hepatic damage. In both alcoholic (no. = 93) and non-alcoholic disease (no. = 112) TBA levels correlated better with characteristics consistent with inflammation and Kupffer cell activity than with connective tissue changes. The degree of steatosis had no effect on TBA levels. Of 117 patients with greater than or equal to 5 of 33 possible biopsy score points, 44, or 38%, had normal TBA levels. All patients with biopsy scores greater than or equal to 12 had abnormally high TBA. Although an elevated fasting TBA level is specific for hepatobiliary disease, the test is insensitive and is not appropriate for screening purposes. This applies equally to alcoholic and non-alcoholic liver disease.

Bile Acids and Salts↗

Bone mineral and calcium metabolism before, during and after treatment of osteoporosis with 1 alpha-hydroxyvitamin D3 and calcium.

A series of osteoporotic patients treated for 25 months (average) with 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3) supplemented with calcium were examined in respect of calcium metabolism and bone mineral changes before, during, and 12 months after cessation of treatment. The bone mineral content, which increased during treatment, showed a decreasing post-treatment tendency. The decrease was more obvious in patients with senile osteoporosis. The levels of serum calcium and phosphate stayed within normal levels. The urinary calcium excretion rate, which also rose during treatment, returned to pre-treatment values after discontinuing treatment. Excretion of urinary phosphate, however, showed a tendency towards further decrease. Serum PTH stayed within normal levels, while serum alkaline phosphatase, which was depressed during treatment, rose again after treatment. The investigation speaks in favour of a continuous administration of 1 alpha-OHD3 and calcium which is generally noted to increase bone mineral during long-term treatment.

Adult↗

IgM in primary biliary cirrhosis. Physicochemical and complement activating properties.

In PBC, common features beyond cholestasis and presence of mitochondrial antibodies are signs of complement activation and high levels if IgM. In order to characterize this IgM physicochemically and immunologically, we studied IgM from 15 patients with PBC in comparison with that from patients with high levels of polyclonal IgM without signs of liver disease (idiopathic hyper-IgM-emia) and normals. Agarose electrophoresis, immunofixation, gel filtration, and ultracentrifugation studies gave no evidence of any abnormal IgM populations such as complexes, aggregates, 7S IgM, or oligoclonality. However, IgM in PBC is highly cryoprecipitable, precipitable with 2.5% PEG (mol. wt. 6000) and binds to conglutinin. In addition, purified IgM from PBC patients rapidly converts complement factor C3 in fresh normal serum, mainly via the classical pathway, in contrast to IgM in the same concentration from normals or patients with idiopathic hyper-IgM-emia. IgM from PBC patients behaves like an immune complex, although it has the same molecular size and electrophoretic properties as normal IgM. No evidence of any antigen(s) bound to IgM in vivo in PBC was found in this study.

Antigen-Antibody Complex↗

Demonstration of normal and mutant protein M1 subunits of deoxyGTP-resistant ribonucleotide reductase from mutant mouse lymphoma cells.

From a mutagenized population of mouse T-lymphoma cells (S49) in continuous culture a cell line has been isolated (Ullman, B., Gudas, L. J., Clift, S. M., Martin, D. W., Jr. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 1074-1978) with ribonucleotide reductase activity that is inhibited only 50% by concentrations of dGTP which abolish wild type enzyme activity. Ribonucleotide reductase activity from this dGuo-L cell line retains its normal sensitivity to dATP. The partial sensitivity/partial resistance of the ribonucleotide reductase suggests that the dGuo-L cell line is heterozygous for ribonucleotide reductase, possessing one normal allele and one allele which codes for a dGTP-resistant enzyme. Both homologous and heterologous mixing experiments between the separated nonidentical subunits of ribonucleotide reductase, protein M1 and protein M2, from wild type and dGuo-L cells showed that the dGTP- feedback sensitivity was governed by the source of the protein M1. A partial resolution of two dGuo-L protein M1 components was achieved by chromatography on dextran blue-Sepharose. In order to resolve the two dGuo-L protein M1 components more completely, we introduced into dGuo-L cells a second mutation which conferred resistance of the ribonucleotide reductase to dATP, while the original dGTP resistance was maintained. The chromatography of protein M1 from this latter clone, dGuo-L-Aphid-G5, on dATP-Sepharose resolved two kinetically distinct protein M1 components. The first component was sensitive to dGTP inhibition but stimulated by dATP; the second was absolutely refractory to dGTP but sensitive to dATP inhibition. This confirms the hypothesis that the dGuo-L parent is heterozygous for protein M1, containing one wild type and one mutant allele.

Animals↗

Evidence for genetically independent allosteric regulatory domains of the protein M1 subunit of mouse ribonucleotide reductase.

Ribonucleotide reductase is responsible for the reduction of the 2'-hydroxy moiety of all four ribonucleoside diphosphates to the corresponding deoxyribonucleotides. The overall activity of the enzyme is regulated by the allosteric effectors ATP (activator) and dATP (inhibitor), and the enzyme's substrate specificity is also controlled by nucleotide effectors. For instance, wild type ribonucleotide reductase from mouse T-lymphoma (S49) cells requires dGTP as a positive effector for ADP reduction. This effect of dGTP causes a reciprocal inhibition of CDP reduction. The dGuo-L mutant cell line, resistant to growth inhibition by exogenous deoxyguanosine, contains a nucleotide-binding subunit, protein M1, that conveys to its CDP reductase an insensitivity to dGTP (and dTTP) inhibition. The dGuo-L protein M1 also shows a decreased capacity to use ADP as a substrate, and therefore, the regulation of the substrate specificity is altered in the mutant protein M1. Another mutant cell line, dGuo-200-1, is resistant to deoxyadenosine and its ribonucleotide reductase is abnormally resistant to inhibition by dATP. The isolated mutant protein M1 from dGuo-200-1 cells has a CDP reductase activity which is stimulated by dATP, unlike the wild type enzyme which is inhibited by dATP. It appears that this mutant enzyme has lost the capacity to distinguish between dATP and ATP, but is still sensitive to regulation by dGTP and dTTP. Thus, the site of protein M1 regulating overall activity is altered in the dGuo-200-1 mutant, while the site regulating substrate specificity is normal. These characteristics of the mutants provide genetic evidence for two independent allosteric domains of protein M1, each responsible for a different aspect of nucleotide sensitivity of ribonucleotide reductase.

Adenosine Triphosphate↗

Ribonucleotide reductase in cultured mouse lymphoma cells. Cell cycle-dependent variation in the activity of subunit protein M2.

Ribonucleotide reductase is responsible for the production of the deoxyribonucleotides required for DNA synthesis. The enzyme is composed of two dissociable subunits, proteins M1 and M2, which are inactive alone, but are fully active when combined. From mouse S49 T lymphoma cells we have isolated and separated the two subunits and used each for determining the activity of the complementary subunit in extracts from cells of different phases in the cell cycle. Treatment of S49 cells with cAMP analogs (e.g. Bt2cAMP) results in the protein kinase-dependent arrest of the cells in the G1 phase of the cell cycle. Ribonucleotide reductase (holoenzyme) activity fell in S49 cells treated for more than 16 h with Bt2cAMP but was unchanged during short term treatments. The activity of protein M2 was decreased in parallel to the overall activity of ribonucleotide reductase, while protein M1 activity changed less. Removal of bt2cAMP after 24 h exposure resulted in increased holoenzyme and protein M2 activities. Centrifugal elutriation of exponentially growing S49 cells separated cells into a 90% pure G1 cell population a mixture of G1 and early S phase cells and a 95% pure S phase/G2 cell population. The specific catalytic activity of protein M1 was the same in all these fractions while that of protein M2 was decreased 60% in the G1 cell population. These results demonstrate that the ribonucleotide reduction necessary for DNA synthesis is regulated in a cell cycle-dependent fashion by the activity of the protein M2 subunit of ribonucleotide reductase.

Animals↗

Effect of bile acid gavage or vagotomy and pyloroplasty on gastrointestinal carcinogenesis.

Possible promotion of MNNG-induced gastrointestinal carcinogenicity was evaluated in male Wistar rats exposed to unconjugated bile acid given as gavage or as obtained through truncal vagotomy plus pyloroplasty. No significant difference was found compared with the relevant control groups. Even though gastroduodenal erosions were found more frequently in the bile acid gavage and MNNG groups than in MNNG-treated controls, secondary deconjugated bile acids apparently did not reach optimal promoting concentrations. In contrast to partial gastrectomy, vagotomy and pyloroplasty does not increase the tumor yield in the rat.

Adenocarcinoma↗

A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man.

1. Intravenous infusions of L-valine (600 mumol/min), L-isoleucine (150 mumol/min), L-leucine (300 mumol/min) and a mixture of the three branched-chain amino acids (70% L-leucine, 20% L-valine, 10% L-isoleucine; 270 mumol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P less than 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.

Adult↗

IgM deposition in skin biopsies from patients with primary biliary cirrhosis.

Immunofluorescence studies on skin biopsies from 14 patients with primary biliary cirrhosis (PBC) showed granular papillary deposition of IgM in all. In addition, 6 patients had C3 deposition. Control patients with various other liver diseases, idiopathic high plasma levels of igM and extrahepatic cholestasis were only sporadically positive for IgM and not at all for C3. IgM deposition in dermal papillae in PBC does not merely reflect high plasma IgM levels or cholestasis but probably represents an immunochemically abnormal IgM population.

Biopsy↗

Pernicious anemia as a risk factor in gastric cancer. The extent of the problem.

We have analyzed the prevalence of pernicious anemia (PA) in all patients with autopsyverified gastric carcinoma (GC) registered during 1958-76 in a Swedish city, with one Department of Pathology serving approximately 240 000 inhabitants and with a high autopsy frequency. The prevalence was compared to that in a reference group of 917 sex- and age-matched individuals without GC. PA was found in 19 persons, 2.1%, (7 males and 12 females) in the GC group and in 13 persons, 1.4%, (5 males and 8 females) in the reference group. This difference is not significant (p less than 0.15). After exclusion of individuals with PA known for less than 5 years before death, the corresponding figures were 16 in the GC group against 8 in the control group. This difference is significant (p less than 0.05). Regarding individuals with a diagnosis of PA for greater than 10 or greater than 15 years, the prevalence was twice as high in the GC as in the reference group. The differences were again insignificant (p less than 0.10). PA as a risk factor for the development of GC has been overestimated probably due to inadequate reference groups. Only 2% of all GCs are associated with PA. Large-scale preventive search for GC in PA patients is thus unjustified.

Age Factors↗