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T Nilsson

Publications and source records attributed to T Nilsson.

At least 19 recordsLinked to original sources
PubMed1992

Proton transfer during the reaction between fully reduced cytochrome c oxidase and dioxygen: pH and deuterium isotope effects.

The pH dependence of proton uptake and electron transfers during the reaction between fully reduced cytochrome c oxidase and oxygen has been studied using the flow-flash method. Proton uptake was monitored using different pH indicators. We have also investigated the effect of D2O on the electron-transfer reactions. Proton uptake was biphasic throughout the pH range studied (6.3-9.3), and the decrease of the observed rate constants at increasing pH could be described by titration curves with pKa values of 8-8.5. Of the four phases resolved in the redox reaction, the rate constants for the first two were independent of pH, whereas that of the third decreased at increasing pH with a pKa of 7.9. All phases except the first were slower in D2O than in H2O. The values obtained for kH/kD were 1.0 for the first phase, 1.4 for the second and third phases, and 2.5 for the fourth phase. We suggest from these results that the fast phase of proton uptake is initiated by the second phase of the redox reaction and that this step includes a partially rate-limiting internal proton transfer. The third and fourth phases of the redox reaction are suggested to be rate limited by proton uptake from the medium. The pH dependencies of the proton uptake reactions are consistent with the participation of a titrable group in the protein in proton transfer from the medium to the oxygen-binding site.

Animals↗
PubMed1992

Photoinduced electron transfer from tris(2,2'-bipyridyl)ruthenium to cytochrome c oxidase.

Flash photolysis has been used to effect electron transfer from tris(2,2'-bipyridyl)ruthenium(II) to cytochrome c oxidase in the presence of a sacrificial electron donor, aniline. The observation that photoreduction occurs only at low ionic strength and high pH indicates that an electrostatic complex between the ruthenium compound and the enzyme is the reactive species. The reaction was followed at 830, 605, and 445 nm. The initial absorbance changes observed suggest that the copper ion CuA is the preferred electron acceptor and that electron transfer from the excited ruthenium complex takes place in less than 1 microsecond. Some rapid cytochrome a reduction is also observed. Absorbance changes after the initial transients suggest that the reduced CuA then equilibrates with cytochrome a with a rate constant of 2 x 10(4) s-1. Comparison of the absorbance changes at 605 and 445 nm and the kinetic difference spectrum in the Soret region indicate that no reduction of cytochrome a3 takes place. With the oxidized enzyme, no further reactions were detected, whereas, in the peroxide and ferryl intermediates, cytochrome a reoxidizes on a millisecond time scale. The reaction appears biphasic in both intermediates, with rate constants in the range 2 x 10(2) to 4 x 10(3) s-1. This is considerably slower than the maximal rates observed for electron transfer between cytochrome a and the bimetallic site found in earlier work and suggests rate limitation by other processes. The rates obtained for the slower phases are close to the rate for catalysis of cytochrome c oxidation.

2,2'-Dipyridyl↗
PubMed1991

Glucose-induced increase in cytoplasmic pH in pancreatic beta-cells is mediated by Na+/H+ exchange, an effect not dependent on protein kinase C.

Glucose-induced changes in cytoplasmic pH (pHi) were investigated using pancreatic beta-cells isolated from obese hyperglycemic mice. Glucose, at concentrations above 3-5 mM, depolarized the beta-cell and increased pHi, cytoplasmic free Ca2+ ([Ca2+]i), and insulin release. This increase in pHi was dependent on the presence of extracellular Na+ and was inhibited by 5-(N-ethyl-N-isopropyl) amiloride, a blocker of Na+/H+ exchange. Stimulation of protein kinase C with phorbol ester also induced an alkalinization. However, when protein kinase C activity was down-regulated, glucose stimulation still induced alkalinization. At 20 mM glucose, 10 mM NH4Cl induced a marked rise in pHi, paralleled by repolarization, inhibition of electrical activity, and decreases in both [Ca2+]i and insulin release. Reduction in [Ca2+]i was prevented by 200 microM tolbutamide, but not by 10 mM tetraethylammonium. At 4 mM glucose, NH4Cl induced a transient increase in insulin release, without changing [Ca2+]i. Exposure of beta-cells to 10 mM sodium acetate caused a persistent decrease in pHi, an effect paralleled by a small transient increase in [Ca2+]i. Acidification per se did not change the beta-cell sensitivity to glucose, not excluding that the activity of the ATP-regulated K+ channels may be modulated by changes in pHi.

Amiloride↗
PubMed1991

Measurements of cytoplasmic free Ca2+ concentration in human pancreatic islets and insulinoma cells.

In human pancreatic islets an increase in the glucose concentration from 3 to 20 mM raised the free cytoplasmic Ca2+ concentration [( Ca2+]i), an effect being reversible upon withdrawal of the sugar. Depolarization with a high concentration of K+ or the sulphonylurea tolbutamide also raised [Ca2+]i. Addition of extracellular ATP produced a transient rapid rise in [Ca2+]i. Oscillations in [Ca2+]i were observed in the presence of 10 mM glucose. Insulinoma cells responded to glucose and tolbutamide with increases in [Ca2+]i, whereas the sulphonamide diazoxide caused a decrease in [Ca2+]i. These findings confirm previous results obtained in rodent beta-cells.

Adult↗
PubMed1991

Interaction with the inositol 1,4,5-trisphosphate receptor promotes Ca2+ sequestration in permeabilised insulin-secreting cells.

Electropermeabilised insulin-secreting RINm5F cells sequestered Ca2+, resulting in a steady-state level of the ambient free Ca2+ concentration corresponding to 723 +/- 127 nM (mean +/- SEM, n = 10), as monitored by a Ca(2+)-selective minielectrode. Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) promoted a rapid and pronounced release of Ca2+. This Ca2+ was resequestered and a new steady-state Ca2+ level was attained, which was always lower (460 +/- 102 nM, n = 10, P less than 0.001) than the steady-state Ca2+ level maintained before the addition of Ins(1,4,5)P3. Whereas the initial reuptake of Ca2+ subsequent to Ins(1,4,5)P3 stimulation was relatively slow, the later part of reuptake was fast as compared to the reuptake phases of a pulse addition of extraneous Ca2+. In the latter case the uptake of Ca2+ resulted in a steady-state level similar to that found in the absence of Ins(1,4,5)P3. Addition of Ins(1,4,5)P3 under this condition resulted in a further Ca2+ uptake and thus a lower steady-state Ca2+ level. Heparin, which binds to the Ins(1,4,5)P3 receptor, also lowered the steady-state free Ca2+ concentration. In contrast to Ins(1,4,5)P3, inositol 1,3,4,5-tetrakisphosphate was without effect on Ca2+ sequestration. These findings are consistent with the presence of a high-affinity Ins(1,4,5)P3 receptor promoting continuous release of Ca2+ under basal conditions and/or the Ins(1,4,5)P3 receptor being actively involved in Ca2+ sequestration.

Biological Transport↗
PubMed1991

Uptake and release of protons during the reaction between cytochrome c oxidase and molecular oxygen: a flow-flash investigation.

Changes in pH during the reactions of the fully reduced and mixed-valence cytochrome oxidase with molecular oxygen have been followed in flow-flash experiments, using the pH indicator phenol red. Solubilized enzyme as well as enzyme reconstituted into phospholipid vesicles has been studied. With the solubilized enzyme, a biphasic uptake of one proton from the medium was observed, whereas the reconstituted enzyme gave release of 1.3 protons to the extravesicular medium. It is concluded from these results that a total of two to three protons are taken up during oxidation of the fully reduced enzyme. Kinetic analysis suggests that the proton uptake is initiated by the transfer of the third electron to the oxygen binding site. A reaction scheme that integrates proton transfers and oxygen chemistry is presented.

Animals↗
PubMed1991

Outcome of the abduction external rotation test among manual and office workers.

Reactions during the Abduction External Rotation (AER) test were studied among 71 platers and 70 assemblers exposed to vibratory tools and manual work and 45 unexposed white collar workers. The frequency of positive neurological reactions was 31% among the platers, 6% among the assemblers, and 16% among the white collar workers. Platers reported the highest fatigue rates in the shoulder regions during the test. A positive association was noted between a pathological AER test and current problems in the neck/scapula or shoulder/upper arm regions, day- or night-time numbness in the hands, tension neck, and carpal tunnel syndrome. Age, length of daily vibration exposure, and vibration acceleration level were also positively associated with a positive AER test outcome. The results indicate that the outcome of the AER test is sensitive to neck and shoulder disorders but also, to some extent, to the carpal tunnel syndrome.

Adult↗
PubMed1991

The membrane spanning domain of beta-1,4-galactosyltransferase specifies trans Golgi localization.

Chimeric cDNAs were constructed so as to generate hybrid proteins in which different parts of the N-terminal domain of the human invariant chain were replaced by equivalent sequences from the trans Golgi resident enzyme, beta-1,4-galactosyltransferase. The cytoplasmic and membrane spanning domains of galactosyltransferase were found to be sufficient to retain all of the hybrid invariant chain in trans Golgi cisternae as judged by indirect immunofluorescence, treatment with brefeldin A and immuno-electron microscopy. As few as ten amino acids corresponding to the lumenal half of the membrane spanning domain of the Golgi enzyme sufficed to localize most of the hybrid invariant chain to the trans cisternae. A cytoplasmic domain was necessary for complete retention as assessed by flow cytofluorometry but could be provided either by galactosyltransferase or by invariant chain. This suggests that the cytoplasmic domain plays a role accessory to the membrane spanning domain, the latter mediating compartmental specificity.

Amino Acid Sequence↗
PubMed1991

Retinol-binding protein and transthyretin expressed in HeLa cells form a complex in the endoplasmic reticulum in both the absence and the presence of retinol.

To establish a suitable experimental system for studies of the interaction of retinol-binding protein (RBP) with transthyretin (TTR) we have expressed the corresponding cDNAs in HeLa cells. To investigate whether complex formation might occur already in the endoplasmic reticulum (ER), the C-terminal ER retention signal, KDEL, was attached to TTR. The tetrameric TTR-KDEL fusion protein was retained in the ER of HeLa cells. When RBP was co-expressed with TTR-KDEL, RBP was retained intracellularly. A cDNA-encoding purpurin, a protein which is 50% identical to RBP, was then expressed together with TTR-KDEL. Purpurin was not retained intracellularly and did not bind to TTR coupled to Sepharose. The effect of the vitamin A status on the secretion of TTR and RBP was examined. While TTR expressed alone was not retained intracellularly, TTR was retained in vitamin A-deficient cells when co-expressed with RBP. Addition of retinol stimulated rapid secretion of both proteins. These results demonstrate that TTR can form a complex with RBP in the ER. The data suggest that RBP and TTR are secreted as a complex.

Anthraquinones↗
PubMed1991

Treatment of symptomatic metastatic prostatic cancer with cyproterone acetate versus orchiectomy: a prospective randomized trial.

During a 2-year period, 37 patients with symptomatic metastatic prostatic cancer were included in a prospective randomized phase-III trial. Nineteen patients were randomized to subcapsular orchiectomy, and 18 to cyproterone acetate (CPA) treatment with a dose of 50 mg b.i.d. The median age of the patients was 74 years (range 48-88 years), with no differences between the treatment groups. At 3, 6, and 12 months after initiation of the therapy and then every 6 months, patients were clinically and biochemically examined, and isotope scans and X-rays were performed. All patients were followed until death. Relief from symptoms was found following 3 months of treatment in 70.6% (95% confidence limits = 44.0-89.7%) of the patients treated with CPA, and in 83.3% (95% confidence limits = 58.6-96.4%) of the orchiectomized patients. The median time to relapse was 9 months in the CPA group, and 11 months in the orchiectomy group (p greater than 0.05). The median survival time was 13 months, with no differences between the groups. The treatment of advanced prostatic cancer with CPA is found to be a valuable alternative to orchiectomy.

Adenocarcinoma↗
PubMed1991

Cystic duct remnants and biliary symptoms after cholecystectomy. A randomised comparison of two operative techniques.

To assess the importance of cystic duct remnants in causing biliary symptoms after cholecystectomy 80 patients undergoing routine cholecystectomy were randomised to have conventional cholecystectomy (n = 40) or cholecystectomy with removal of the whole cystic duct (n = 40). Fifteen were withdrawn, leaving 65 (32 who had standard cholecystectomy and 33 who had cholecystectomy by the new technique) for analysis. Thirty of the 32, and 27 of the 33, were available for follow up one, two, three, and eight years after operation; 11 of the 30 (37%) compared with 23 of the 27 (85%) were free of biliary symptoms during the eight year period (p less than 0.001). We conclude that removal of the stump of the cystic duct improves the success rate of cholecystectomy in the treatment of gallstones.

Abdominal Pain↗
PubMed1979

N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark.

A variable but often significant proportion of urinary bladder cancer in urban areas can be attributed to occupational and cultural (cigarette smoking) situations associated with exposures to various arylamines. The variable N-acetylation of carcinogenic arylamines by human hepatic enzyme systems, the known genetic regulation and polymorphic distribution of this enzyme activity in humans, and the known enhanced susceptibility of individuals with the genetically-distinct "slow acetylator" phenotype to various arylamine toxicities, has prompted examination of possible correlations between N-acetyltransferase phenotype and urinary bladder cancer risk in rural and urban populations. In this context, N-acetylation is viewed as a component of detoxication pathways with respect to arylamine bladder carcinogenesis. In preliminary utilizations of this approach, a population of urban urinary bladder cancer patients from Copenhagen, Denmark displayed a 13% excess (p = 0.065) of individuals with the slow acetylator phenotype (46/71 = 64.8%) when compared to a Danish control population (38/74 = 51.4%). These data are consistent with the possibility that arylamines may play an etiological role in bladder cancer in this locale and that slow acetylator individuals may be at higher relative risk (1.74) than rapid acetylator individuals. As 95% of patients reported histories of smoking, it was not possible to isolate and examine smoking factors. In contrast, a population of rural urinary bladder cancer patients from Lund, Sweden, where bladder cancer incidence (20/100,000) (1971) is lower than in Copenhagen (43.8/100,000) (1968-72), no difference in slow acetylator distribution was observed between bladder cancer (80/115 = 69.6%) and Swedish control (79/118 = 66.9%) populations, indicating a relative lack of involvement of arylamines in the etiology of rural bladder cancer. Populations of "spontaneous" bladder cancer patients would be expected to contain variable portions of disease related to arylamine exposure and would be less likely to display a detectable correlation than would an industrial population with documentable arylamine exposure. Consequently, confirmation of this hypothesis is being pursued by examination of industrial populations in an effort to obtain an empirical estimate of relative risk for slow and rapid acetylator phenotypes. These studies involve exposure-matched workmen both with and without bladder cancer.

Acetyltransferases↗
PubMed1979

Characterization of different regions of the normal human urinary bladder by means of scanning electron microscopy.

A study of the normal human urinary bladder and the proximal urethra was performed using scanning electron microscopy (SEM). Biopsies were evaluated from 27 male patients with benign prostatic hyperplasia, without history or sign of urinary tract malignancy and with cystoscopically normal mucosal finding. The specimens were obtained from the dome, the side-walls and the trigone of the bladder. The characteristic surface architecture of the transitional epithelium was observed in different anatomical regions of the human urinary bladder.

Aged↗
PubMed1979

Surface characteristics of malignant human urinary bladder epithelium studied with scanning electron microscopy.

Biopsies were obtained from 28 male and seven female patients with cystoscopically and histologically confirmed urinary bladder carcionoma. Tissue specimens for light microscopy and scanning electron microscopy (SEM) were obtained from the tumours as well as from cystoscopically tumour-free mucosa of the dome, the lateral walls and the trigone of the urinary bladder and also from the proximal urethra. Certain surface structural changes, which seem to represent malignancy, present in different regions of the urinary bladder were detected by SEM, although not visible by light microscopy.

Aged↗
PubMed1979

Scanning electron microscopy of exfoliated malignant and non-malignant human urothelial cells.

Midstream urine samples were taken from 35 patients with histologically diagnosed urinary bladder carcinoma, from 27 patients without history or sign of malignancy or infection in the urinary tract, and from eight patiens with cystitis. The urine was filtered through Millipore filters, or Nuclepore filters, pore size 5.0 microns, on which the cells were caught. From the same patients biopsies were obtained from different anatomic regions of the urinary bladders as well as from the carcinomas that were present. The filters and the biopsies were examined with scanning electron microscopy (SEM). The exfoliated cells trapped on the filters were in good morphological condition. Idential characteristics of the cell surface morphology were recognized in the biopsies and the exfoliated cells from each patient. In non-malignant cases the cells displayed the regional morphological charcteristics of the urinary bladder. Bacteria and an increased number of red and white blood cells were attached to the cell surface of numerous exfoliated cells in patients with cystitis, but no pleomorphic microvilli were detected in these patients. In cases of malignancy exfoliated cells with pleomorphic microvilli on their surface were detected. A large majority of the exfoliated cells shed in the urine with pleomorphic microvilli on their surfaces still retained enough regional surface characteristics to determine their origin. Some of the cells were completely covered with pleomorphic microvilli and it was impossible to determine their origin.

Biopsy↗
PubMed1979

An indirect method to examine forces affecting Courvoisier's oblique gall-bladder incision.

The aim of this study is to establish a method by which the maximum forces attacking Courvoisier's oblique gall-bladder incision can be evaluated. Nine well-informed patients served as subjects. Four investigations were made: pre-, per-, and two postoperative. The pre- and postoperative maximum isometric muscle strength in pulling forward were measured with a dynamometer. Simultaneously the IEMG was obtained. A muscle tensiometer was used for registration of the peroperative muscle pull of the right abdominal rectus muscle, and IEMG obtained simultaneously. The IEMG makes a calculation of the pre- and postoperative rectus muscle pull possible. The study seems to indicate that the most realistic estimation of the forces attacking the wound in the early postoperative phase is a preoperative measurement of the maximum force in pulling forward (attempted trunk bending). If ruptures in the wound occur during the extubation, ruptures would very likely also occur in the early postoperative phase. Eight weeks after the operation the right rectus muscle has regained its preoperative strength.

Abdominal Muscles↗
PubMed1978

Stimulation of immune reactivity by methoxy-substituted glycerol ethers incorporated into the feed.

In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes.

Animals↗