[A special psychogeriatric admission unit gives better care].
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Biomedical subjects
Publications and source records attributed to L Berglund.
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Positron emission tomography (PET) is a new tracer technique by which short-lived radionuclides, such as 11C are used for labeling drugs, amino acids and other compounds. The concentration in the various organs is determined non-invasively after I.V. injection. Positrons, emitted by 11C attract an electron, and the two masses are annihilated by emitting photons. These can be registered by external detectors. Measurement of the radioactivity per volume of tissue as a function of time is accomplished by computerized processing of the data. The PET technique may be used for studies of the kinetics of the injected compound in different organs of the body. However, PET registers only the total radioactivity meaning that the measured 11C-radioactivity represents the sum of the parent compound and the radiolabelled metabolites. Chemical and radiochemical analyses in various body fluids may then help to interpret the PET images.
A gastrin gene was isolated from a genomic library of human DNA. The human gastrin gene is about 4100 base pairs long and contains two intervening sequences. Thus, a 3500-base-pair intervening sequence is located 5 base pairs proximal to the ATG initiator codon, while a 129-base-pair intervening sequence separates the region coding for the principal hormonal form of gastrin, the heptadecapeptide, from the region coding for the major amino-terminal portion of the gastrin precursor. The 5' flanking region of the gene contains the conserved sequences, T-A-T-A-A and G-A-C-T-C-A-T-A-T, in positions similar to those of other eukaryotic genes.
By use of Positron Emission Tomography (PET), dynamic studies of the metabolism within the feto-maternal unit can be performed using various tracers. Many compounds like amino acids, carbohydrates, fatty acids and drugs can be performed using various tracers. Many compounds like amino acids, carbohydrates, fatty acids and drugs can be labelled with 11C and used as tracers. 11C-labelled L- or D-methionine was injected intravenously into pregnant Rhesus monkeys. The distribution of the radioactivity in maternal muscles, aorta, placenta and the liver of the fetus was quantitatively estimated as a function of time. Simultaneously blood, urine and amniotic fluid samples were analyzed for 11C-activity. The distribution of 11C between the high and the low molecular fraction of plasma (MW greater than 5000) was studied after gel filtration. Both when 11C-L- and D-methionine were given, the radioactivity rapidly crossed the placenta and was accumulated in the fetal liver. In the 11C-L-methionine experiments, about 70 per cent of the radioactivity in plasma was found in the high molecular fraction one hour after injection. A greater part of 11C-D-compared to 11C-L-activity was excreted in the urine.
During the five-year period 1977-1981, 120 twins were delivered at the University Hospital, Uppsala, Sweden. 6 or 5%, were delivered by the combined vaginal-abdominal route. There was no case of foetal death among the second twins. Only one second twin had an Apgar score of less than eight at five minutes. Four mothers received blood transfusion because of blood loss related to the operation and two mothers developed fever during the puerperium. It is concluded that caesarean section may well be performed for rapid delivery of the compromised second twin, although the maternal morbidity is substantial.
The aim of this study was to determine if a three-day treatment of lower urinary tract infection (UTI) is effective. 215 women with symptoms of lower UTI, seen in general practice, were randomly allocated to a double-blind study and given either amoxycillin 1000 mg twice a day for three days or trimethoprim 90 mg/sulphadiazine 410 mg (co-trimazine) 2 tablets initially, then one tablet twice daily for three days. 157 women (73%) had significant bacteriuria. Therapeutic efficacy was evaluated in 146 patients. One week after treatment had started, 88% of the women in the amoxycillin group and 100% in the co-trimazine group were cured (p less than 0.01). After a follow-up period of four weeks, the cumulative relapse frequencies were 19% and 9% respectively. Adverse reactions were mild in most cases. Two patients, both on co-trimazine, had to discontinue treatment because of nausea and vomiting. Vulvovaginal irritation was more often reported by women treated with amoxycillin (n = 8) than by those treated with co-trimazine (n = 1) (p less than 0.05). It is concluded that a three-day course of amoxycillin or co-trimazine in lower UTI is safe, causes few adverse reactions, is simple to administer and comfortable for the patient. Co-trimazine seems to be more effective than amoxycillin.
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Hormone-sensitive lipase of rat adipose tissue was partially purified. The enzyme retained its capacity to be activated by cyclic AMP-dependent protein kinase throughout purification. When the partially purified 32P-labeled preparation was subjected to two-dimensional gel electrophoresis, the enzyme activity was found to be associated with a 32P-labeled protein of molecular weight 84 000. The result suggests that this 32P-labeled protein represents hormone-sensitive lipase or the catalytic subunit of the enzyme.
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In this double-blind study, the clinical tolerance of high doses of bacampicillin hydrochloride (800 mg t. i. d.) and of pivampicillin base (700 mg t. i. d.) administered for ten days were compared in out-patients with acute urinary tract infections. The clinical response was comparable with that previously reported for those antibiotics. Upper gastrointestinal side-effects were more common after treatment with pivampicillin and were reported in 9/38 patients compared to 3/34 patients treated with bacampicillin. The duration of the symptoms of the side-effects was also more prolonged after pivampicillin than after bacampicillin.
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Pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) type L was partly purified from rat kidney. During the last two purification steps, the incorporation of [32P]phosphate into protein on incubation with [32P]ATP and cyclic 3',5'-AMP-dependent protein kinase was found to parallel the pyruvate kinase activity. After phosphorylation of the enzyme, a major radioactive band with a molecular weight of 57 000 was found on polyacrylamide gel electrophoresis [32P]Phosphorylserine was isolated from the kidney pyruvate kinase. Immunological identity was found between the liver and kidney pyruvate kinases type L. By autoradiography of high-voltage electropherograms after partial acid hydrolysis of the phosphorylated rat liver and kidney pyruvate kinases type L, identical results were obtained. The affinity for phosphoenolpyruvate was found to be decreased by phosphorylation of the enzyme with a change in the apparent Km from 0.15 mM to 0.35 mM. After incubation of the phosphorylated kidney pyruvate kinase with phosphatase the phosphoenolpyruvate saturation curve was found to be identical to that for the unphosphorylated enzyme. Thus, the activity of the rat kidney pyruvate kinase type L is with all probability regulated by a reversible phosphorylation-dephosphorylation reaction, thereby indicating that hormonal regulation of gluconeogenesis via cyclic AMP may be of importance in the renal cortex.
Pyruvate kinase type A was purified from pig kidney with a yield of 9%. The final enzyme fraction had a specific activity of 500 units/mg of protein. The enzyme appeared to be homogeneous on polyacrylamide gel electrophoresis in detergent and in ultracentrifugation experiments. The molecular weight of the enzyme was found to be 210,000 with the use of ultracentrifugation and 249,000 at gel chromatography. The sedimentation coefficient (S degrees 20, w) was calculated to be 9.8 S. For the reduced and alkylated pyruvate kinase, a molecular weight of 60,000 was found with the use of several methods. The Stokes radius for the enzyme was calculated to be 56 A. No NH2-terminal amino acid was detected in the enzyme, and the only findings in carbohydrate analyses of the kidney pyruvate kinase were trace amounts of glucose. The isoelectric point of the enzyme was estimated to be pH 5.6. Pig kidney pyruvate kinase type A was not phosphorylated on incubation with ATP and cyclic 3':5'-AMP-dependent protein kinase. The amino acid compositions of pig kidney and pig muscle pyruvate kinases were very similar and differed clearly from that of pig liver pyruvate kinase.
The phosphorylation of pig liver pyruvate kinase by cyclic adenosine 3':5'-monophosphate-dependent protein kinase has been studied. For comparison, mixed histone and a synthetic heptapeptide were also used as substrates. Protein kinase was purified by chromatography on DEAE-cellulose, hydroxyapatite, and Sephadex G-200. The enzyme was stimulated by cyclic AMP with apparent Ka values of 2.5 and 0.8 x 10-7 M for pyruvate kinase and histone substrates, respectively. Divalent cations were essential for the activity of the protein kinase. Variation of the concentration of ATP resulted in approximately straight lines in Lineweaver-Burk plots for the phosphorylation of both pyruvate kinase and mixed histone. The apparent Km values for ATP were 21 and 11 muM, respectively. The phosphorylation rate increased with the concentration of pyruvate kinase even at a concentration of 2 muM pyruvate kinase. At a high ionic strength, the phosphorylation rate of both pyruvate kinase and histone decreased. The phosphorylation rate varied markedly with pH in imidazole/HC1 and Tris/HC1 buffers. At slightly alkaline pH values, pyruvate kinase was phosphorylated at a much higher rate than pH7, but this was not the case for histone. At pH 8.5, the phosphorylation rate of pyruvate kinase was 3.5 times the rate at pH 7, while the corresponding increase for the histone phosphorylation was 50 per cent. In potassium phosphate buffers, the phosphorylation rate of both substrates did not change significantly over the pH range studied. Arrhenius' plots of the protein kinase reaction resulted in a break at about 10 degrees when pyruvate kinase was used as substrate, whereas a straight line was obtained when using histone. The negative allosteric effectors of pyruvate kinase, alanine, and phenylalanine, increased the phosphorylation rate of pyruvate kinase at pH 8 by 50 and 120 per cent, respectively. The same effectors did not influence the phosphorylation rate of mixed histone or a synthetic heptapeptide. It is concluded that the conformations adopted by pyruvate kinase in the presence of allosteric inhibitors make it a better substrate for the protein kinase.
A number of hematological variables have been investigated and followed during a hospital stay in a group of 34 non-cirrhotic male alcoholics after acute drinking bouts. The most prominent findings were a rise in reticulocytes, a fall in serum iron and a rise in WBC, especially with respect to the lymphocytes. HB and hematocrit values both fell during hospitalization, while ESR and serum haptoglobin rose. No change was observed in the platelet count. It is concluded that alcohol has marked effects on the hematological system even in subjects without serious liver damage. The results underline the importance of an adequate knowledge of the patient's alcohol habits in the investigation of obscure hematologic abnormalities.
The effect of cyclic-AMP-dependent phosphorylation on the activity of isolated pig liver pyruvate kinase was studied. It was found that the major kinetic effect of the phosphorylation was to reduce the affinity for the substrate phosphoenolpyruvate, K0.5 for this substrate increasing from 0.3 to 0.9 mM upon phosphorylation. The cooperative effect with phosphoenolpyruvate was enhanced, the Hill constant nH increasing concomitantly from 1.1 to 1.5. V was unaltered. The change in activity occurred in parallel with the phosphate incorporation, except during the initial part of the reaction, when inactivation was correspondingly slower. The affinity for the second substrate ADP was unchanged, with an apparent Km of 0.3 mM at saturating concentration of phosphoenolpyruvate. Likewise, the requirement for potassium was unaffected, whereas the phosphoenzyme required a higher concentration of magnesium ions for maximal activity, compared with the control enzyme. The inhibitory effect of the phosphorylation was counteracted by positive effectors, fructose 1,6-biphosphate in micromolar concentrations completely activated the phosphoenzyme, resulting in an enzyme with properties similar to the fructose 1,6-biphosphate-activated unphosphorylated enzyme, with K0.5 for phosphoenolpyruvate about 0.025 mM and with a Hill constant of 1.1. Hydrogen ions were also effective in activating the phosphoenzyme. Thus, when pH was lowered from 8 to 6.5 the inhibition due to phosphorylation was abolished. The phosphoenzyme was sensitive to further inhibition by negative effectors such as ATP and alanine. 2 mM ATP increased K0.5 for phosphoenolpyruvate to 1.5 mM and nH to 2.3. The corresponding values with alanine were 1.3 mM and 1.9. Phosphorylation is thought to be an additional mechanism of inhibition of the enzyme under gluconeogenetic conditions.