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Biomedical subjects

A Andersson

Publications and source records attributed to A Andersson.

At least 127 records · Page 7Linked to original sources

Nitric oxide and pancreatic islet blood flow after induced portal hypertension in rats.

Portal hypertension (PH) is associated with a hyperdynamic splanchnic circulation, partially mediated by nitric oxide-dependent mechanisms. The aim of the present study was to evaluate the influence of PH and nitric oxide on pancreatic islet blood flow. PH was induced by a calibrated stenosis of the portal vein in male Sprague-Dawley rats. Control were sham-operated. Ten days later pancreatic, duodenal, colonic, and arterial hepatic blood flows were measured with microspheres. All splanchnic blood flow values were markedly increased in the PH rats. The fraction of whole pancreatic blood flow diverted through the islets increased from approximately 5 to 15%. Intravenous administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine (25 mg/kg body weight) in rats with PH 10 min before blood flow measurements decreased pancreatic, duodenal, colonic, and arterial hepatic blood flow to control values. Pancreatic islet blood flow was also decreased, but more markedly than that of the whole pancreas. Pancreatic islet morphology was normal, and the rate of islet cell replication was not influenced. PH induced a preferential increase in pancreatic islet blood flow, which is likely to be associated with an increased production of nitric oxide.

Animals↗

Assistive technology selection: a study of participation of users with rheumatoid arthritis.

A new program based on improved user participation for the selection of assistive devices was implemented and its effectiveness and efficiency assessed. The intervention was compared with traditional routines. The study population comprised persons with rheumatoid arthritis who lived in two communities in Sweden. The selection process yielded increased user participation, user satisfaction, an increased number of prescriptions, and consequently also higher costs. The outcome measures showed more vague improvements. No improvement in functional ability was found regarding pain and difficulty with daily activities in the two study groups, but an increased use of assistive devices was found among women below 64 years in the intervention group (p = 0.001). Women below 64 years in the intervention group rated an improved health-related quality of life regarding both the total score (p = 0.017) and the underlying dimensions of physical function (p = 0.012). Even though the intervention yielded positive results on process-variables as increased user participation and an increased number of prescribed assistive devices, only women below 64 years showed an increased use of assistive devices in daily activities and an improved health related quality of life.

Activities of Daily Living↗

Evolutionary relationships among members of the genus Chlamydia based on 16S ribosomal DNA analysis.

Nucleotide sequences from strains of the four species currently in the genus Chlamydia, C. pecorum, C. pneumoniae, C. psittaci, and C. trachomatis were investigated. In vitro-amplified RNA genes of the ribosomal small subunit from 30 strains of C. pneumoniae and C. pecorum were subjected to solid-phase DNA sequencing of both strands. The human isolates of C. pneumoniae differed in only one position in the 16S rRNA gene, indicating genetic homogeneity among these strains. Interestingly, horse isolate N16 of C. pneumoniae was found to be closely related to the human isolates of this species, with a 98.9% nucleotide similarity between their 16S rRNA sequences. The type strain and koala isolates of C. pecorum were also found to be very similar to each other, possessing two different 16S rRNA sequences with only one-nucleotide difference. Furthermore, the C. pecorum strains truncated the 16S rRNA molecule by one nucleotide compared to the molecules of the other chlamydial species. This truncation was found to result in loss of a unilaterally bulged nucleotide, an attribute present in all other eubacteria. The phylogenetic structure of the genus Chlamydia was determined by analysis of 16S rRNA sequences. All phylogenetic trees revealed a distinct line of descent of the family Chlamydiaceae built of two main clusters which we denote the C. pneumoniae cluster and the C. psittaci cluster. The clusters were verified by bootstrap analysis of the trees and signature nucleotide analysis. The former cluster contained the human isolates of C. pneumoniae and equine strain N16. The latter cluster consisted of C. psittaci, C. pecorum, and C. trachomatis. The members of the C. pneumoniae cluster showed tight clustering and strain N16 is likely to be a subspecies of C. pneumoniae since these strains also share some antigenic cross-reactivity and clustering of major outer membrane protein gene sequences. C. psittaci and strain N16 branched early out of the respective cluster, and interestingly, their inclusion bodies do not stain with iodine. Furthermore, they also share less reliable features like normal elementary body morphology and plasmid content. Therefore, the branching order presented here is very likely a true reflection of evolution, with strain N16 of the species C. pneumoniae and C. psittaci forming early branches of their respective cluster and with C. trachomatis being the more recently evolved species within the genus Chlamydia.

Animals↗

Moderate exercise at energy balance does not affect 24-h leucine oxidation or nitrogen retention in healthy men.

Short-term metabolic experiments have revealed that physical exercise increases the oxidation of leucine, which has been interpreted to indicate an increased requirement for dietary protein in physically active subjects. Because it may be inaccurate to extrapolate measurements of amino acid oxidation made over a few hours to the entire day, we have carried out a continuous 24-h intravenous [1-13C]leucine/[15N]urea tracer study in eight healthy adult men. Their diet supplied 1 g protein.kg-1.day-1, and exercise (mean maximal O2 consumption 46%) was for 90 min during the 12-h fast and 12-h fed periods of the day. Subjects were adapted to the diet and exercise regimen for 6 days. Then, on day 7, they were dressed in the University of Uppsala energy metabolic unit's direct calorimeter suit, were connected to an open-hood indirect calorimeter, and received the tracers. Exercise increased leucine oxidation by approximately 50 and 30% over preexercise rates for fast and fed periods, respectively. This increase amounted to approximately 4-7% of daily leucine oxidation. Subjects remained in body leucine equilibrium (balance -4.6 +/- 10.5 mg.kg-1.day-1; -3.6 +/- 8.3% of intake; P = not significant from zero balance). Therefore, moderate exercise did not cause a significant deterioration in leucine homeostasis at a protein intake of 1 g.kg-1.day-1. These findings underscore the importance of carrying out precise, continuous, 24-h measurements of whole body leucine kinetics; this model should be of value in studies concerning the quantitative interactions among physical exercise, energy/protein metabolism, and diet in humans.

Adult↗

Mechanisms of defective glucose-induced insulin release in human pancreatic islets transplanted to diabetic nude mice.

We have previously observed that human islets, transplanted under the kidney capsule of hyperglycemic nude mice, show a longlasting impairment in glucose-induced insulin release. To investigate the cause(s) of this phenomenon, we transplanted human islets into normoglycemic or alloxan-diabetic nude mice for a 4- to 6-week period. In a third experimental group, aimed at evaluating reversibility of hyperglycemia effects, diabetic nude mice bearing a human islet graft were cured by a second intrasplenic transplant of mouse islets, and the human islets were exposed to a further 2 weeks of normoglycemia. Four to 6 weeks of hyperglycemia induced a severe impairment of glucose- and arginine-induced insulin release, as demonstrated by perfusion of the graft-bearing kidney. This defective release was not restored by a subsequent 2-week period of normoglycemia, and it was accompanied by normal (pro)insulin biosynthesis, glucose oxidation, and expression of insulin messenger RNA. Taken together with our previous study, these observations indicate that impaired glucose metabolism, depletion of insulin messenger RNA, decreased (pro)insulin biosynthesis, increased glycogen accumulation, and depletion of insulin reserves cannot explain the deleterious effects of the diabetic state on human islet insulin release. This, and the similar inhibition of glucose- and arginine-induced insulin release, suggest that prolonged hyperglycemia may exert its deleterious effect on insulin release at a step distal to closure of ATP-sensitive K-channels.

Adult↗

Marginal folate deficiency as a possible cause of hyperhomocystinaemia in stroke patients.

It has been reported that patients with vascular disease seem to increase their concentration of plasma homocysteine after the acute episode, whereas reexamined control subjects do not change their concentration of plasma homocysteine over time. Since the main determinants of plasma homocysteine are serum cobalamin, blood folate and serum creatinine we measured these quantities in 20 control subjects and 49 stroke patients in the acute phase and at reexamination 1.5-2 years after acute stroke onset. There were no significant differences between the levels of blood folate, serum cobalamin and serum creatinine in the acute and convalescent phase of all 49 stroke patients. However, we noted a significant decrease of blood folate concentrations in a subgroup of patients (n = 25) who had increased plasma homocysteine concentrations. Thus the increase in plasma homocysteine concentrations in this group of patients may partly be caused by a marginal folate deficiency.

Aged↗

Blood flow-independent accumulation of cisplatin in the guinea pig cochlea.

Considerable interindividual variability in the ototoxic effect of cisplatin has become the unpredictable dose-limiting factor in its use as curative as well as palliative therapy. The drug accumulates in highly vascular areas in the cochlea, causing dose-related hair cell loss. The purpose of this study was to assess blood flow-dependent aspects of cisplatin absorption in the cochlea in order to better understand factors that may influence cisplatin-induced ototoxicity. The effect of reduced cochlear blood flow on the ototoxic action of cisplatin was studied in guinea pigs. Before cisplatin administration the cochlear vasculature in each animal was unilaterally pre-constricted, by the application of 2% epinephrine to the round window. A 20-30% reduction in cochlear blood flow, assessed by laser Doppler flowmetry, was maintained before and after intravenous infusion of 0.1% cisplatin. Cisplatin infusion affected cochlear blood flow but not vessel conductivity. The cochlear blood flow decrease, maintained by local epinephrine application to the round window during cisplatin infusion, did not alter the cisplatin-induced hearing loss. In addition, the concentration of free cisplatin in scala tympani perilymph did not differ between epinephrine-treated and non-treated ears. Our results indicate that cisplatin transport into the cochlea is not an energy-dependent process in the lateral wall vasculature.

Animals↗

[Ideals in life and professional ethics: on the significance of the idea of a calling in the history of ideas of female care work].

The present article deals with the idea of nursing as a "calling" or "vocation" and its significance for the history of female care work. The female care profession developed during the period 1850-1920. This development is primarily associated with three educational institutions: the Ersta Deaconess institution, the Red Cross and Sophiahemmet. The perception of nursing as a calling underwent a transformation during the above-mentioned period, which is reflected in the profiles of the various institutions. This transformation can be traced from its origins in a Deaconess calling, wherein a deep religious faith and missionary activity were self-evident aspects of the calling, to a "nursing vocation", which begins to resemble a modern professional ethic and where faith in God is no longer considered mandatory. Insofar as one may speak of an "intensive period of development" in the history of this term, it can be localized in the years around the turn of the last century. It was at this point in time that the "calling" aspect was proclaimed with particular vigour, and not only by nurses but also other groups, primarily female professionals not belonging to the working class. However, the nursing profession was singular in its determination to be associated with the idea of a calling, and was also associated in the minds of outsiders as being intimately connected to that idea. In order to facilitate a broad understanding of this powerful emphasis of the nursing profession as a calling, particular attention must be paid to the nurses' own professionalization ambitions, the jealousy with which the medical corps guarded its own professional territory, the economic interests of employers and the culturally-inherited view of women and women's work. All of these factors contribute to the complexity of the term "calling" at the beginning of the twentieth century.

History, 19th Century↗

Cervex-Brush vs. spatula and Cytobrush. A cytohistologic evaluation.

OBJECTIVE: To compare the efficacy of two cervical smear instruments, Cervex-Brush and spatula plus Cytobrush. STUDY DESIGN: Cervical smears were taken before laser ring biopsies in 213 women, who were randomized for the Cervex-Brush or spatula plus Cytobrush (S+C). The cytologic diagnosis was compared to the histologic diagnosis after laser ring biopsy. RESULTS: The correlation between cytology and histology showed comparable concordance (54% and 42%) for the two devices. In 130 (74 with Cervex-Brush and 56 S+C) patients, histology revealed moderate dysplasia or more advanced lesions. Those cases were further analyzed for smear failures. Negative smears were found in 13 cases (10 in the Cervex-Brush and 3 in the S+C group). This difference in favor of S+C was not, however, statistically significant. Significantly more false negative smears were found when endocervical cells were absent and in patients 30-39 years of age. CONCLUSION: Modern sampling devices, such as the Cervex-Brush and S+C, seem to be equally efficient in obtaining dysplastic squamous cells. Other factors of importance for nonrepresentative cervical smears should be studied in order to improve efficacy.

Adult↗

Crystal structure of the ternary complex of 1,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea with NADPH and an active-site inhibitor.

BACKGROUND: The enzyme 1,3,8-trihydroxynaphthalene reductase (THNR) catalyzes an essential reaction in the biosynthesis of melanin, a black pigment crucial for the pathogenesis of the rice blast fungus, Magnaporthe grisea. The enzyme is the biochemical target of several commercially important fungicides which are used to prevent blast disease in rice plants. We have determined the structure of the ternary complex of THNR with bound NADPH and a fungicide, tricyclazole. RESULTS: Crystallographic analysis showed four identical subunits of THNR to form a tetramer with 222 symmetry. The enzyme subunit consists of a single domain comprising a seven-stranded beta sheet flanked by eight alpha helices; the subunit contains a dinucleotide-binding fold which binds the coenzyme, NADPH. Tricyclazole, an inhibitor of the enzyme, binds at the active site in the vicinity of the NADPH nicotinamide ring. The active site contains a Ser-Tyr-Lys triad which is proposed to participate in catalysis. Coenzyme specificity is partly conferred by the interaction of a single basic residue, Arg39, with the 2' phosphate group of NADPH. CONCLUSIONS: The structural model reveals THNR to belong to the family of short chain dehydrogenases. Despite the diversity of the chemical reactions catalyzed by this family of enzymes, their tertiary structures are very similar. In particular THNR has many amino acid sequence identities, and thus most probably high structural similarities, to enzymes involved in fungal aflatoxin synthesis. The structure of THNR in complex with NADPH and tricyclazole provides new insights into the structural basis of inhibitor binding. This new information may aid in the design of new inhibitors for rice crop protection.

Amino Acid Sequence↗

Evidence for a further enterotoxin complex produced by Bacillus cereus.

Out of 321 strains of Bacillus cereus from several sources and isolated in four different countries, 239 (74%) produced cytotoxins. Only 127 (53%) of the cytotoxic strains were positive for the B-component gene of the haemolysin BL (enterotoxin) by polymerase chain reaction (PCR). Western blots using antiserum produced against enterotoxin(s) gave positive results for 199 (83%) of the cytotoxic B. cereus strains. On closer examination of seven of the strains, involved in food poisoning, we found that two strains completely lacked the L2- and B-components (of the haemolysin BL), and two strains were negative for the B-component gene by PCR, but were positive for the L2-component. From our experiments we concluded that there is at least one enterotoxin complex in addition to the haemolysin BL enterotoxin and enterotoxin T.

Animals↗

Toxicity in vivo of different immunosuppressive drugs in fetal porcine pancreatic islets.

Clinical transplantation of fetal porcine islet-like cell clusters (ICC) to kidney transplanted diabetic patients has shown both morphological and biochemical evidence of prolonged xenograft survival, but no effect was seen on the insulin requirement of the transplanted patients. One possible explanation for this relative lack of success might have been the influence of the immunosuppressive drugs on the differentiation of ICC grafts. In this study, the effects of a number of immunosuppressive drugs on ICC differentiation were investigated. Normoglycemic C57BL/6 nu/nu mice were transplanted with 2x3 microliter ICC under the renal capsule. During a four-week period the animals were treated daily with azathioprine (2.0 mg/kg b.wt.), prednisolone (0.5 mg/kg b.wt.), cyclosporine (5.0 mg/kg b.wt.), cyclophosphamide (5.0 mg/kg b.wt.) 15-deoxyspergualin (5.0 mg/kg b.wt.), leflunomide (30 mg/kg b.wt.) or saline. In order to estimate rates of beta-cell DNA synthesis in the ICC grafts the mice were injected with 3H-thymidine one hour before killing and slides of the grafts were evaluated with regard to autoradiographical labeling. Other ICC grafts were evaluated by measurement of their insulin and DNA contents. Both the DNA content of ICC grafts and the beta cell labeling index in the cyclosporine animals were significantly decreased. Perfusion experiments with graft-bearing kidneys of cyclosporine-treated animals showed a significantly decreased insulin secretion in response to glucose plus theophylline. None of the other drugs influenced the differentiation of grafted ICC as evaluated in this study. Thus, it is obvious that cyclosporine inhibits both the growth and functional differentiation of transplanted ICC, which might be one reason for the relative lack of success in the clinical transplantation of porcine ICC to diabetic patients.

Animals↗

Wild-type Escherichia coli cells regulate the membrane lipid composition in a "window" between gel and non-lamellar structures.

Escherichia coli strain K12 was grown at 17, 27, and 37 degrees C. The acyl chain composition of the membrane lipids varied with the growth temperature; the fraction of cis-vaccenoyl chains decreased, and the fraction of palmitoyl chains increased, when the growth temperature was increased. However, the polar head group composition did not change significantly. The equilibria between lamellar and reversed non-lamellar phases of lipids extracted from the inner membrane (IM), and from both the membranes (IOM), were studied with NMR and x-ray diffraction. At temperatures above the growth temperature the lipid extracts formed a reversed hexagonal phase, or a bicontinuous cubic phase, depending on the degree of hydration of the lipids. It was observed that: 1) at equal elevations above the growth temperature, IM lipid extracts, as well as IOM lipid extracts, have a nearly equal ability to form non-lamellar phases; 2) IM extracts have a stronger tendency than IOM extracts to form non-lamellar phases; 3) non-lamellar phases are formed under conditions that are relatively close to the physiological ones; the membrane lipid monolayers are thus "frustrated"; and 4) as a consequence of the change of the acyl chain structures, the temperature for the lamellar gel to liquid crystalline phase transition is changed simultaneously, and in the same direction, as the temperature for the lamellar to non-lamellar phase transition. With a too large fraction of saturated acyl chains the membrane lipids enter a gel state, and with a too large fraction of unsaturated acyl chains the lipids transform to non-lamellar phases. It is thus concluded that the regulation of the acyl chain composition in wild-type cells of E. coli is necessary for the organism to be able to grow in a "window" between a lamellar gel phase and reversed non-lamellar phases.

Escherichia coli↗

N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels.

High levels of lipoprotein(a) (Lp(a)) or homocysteine in plasma have both been associated with an increased risk for premature cardiovascular disease. For both components, the plasma levels are primarily genetically determined, and they have been very restintant to therapeutic approaches. It has been suggested that N-acetylcysteine (NAC) breaks disulphide bonds in Lp(a) as well as between homocysteine and plasma proteins. In the present study we analyze if this mechanism, in vivo, could be used to lower plasma concentrations of Lp(a) and homocysteine. Treatment with NAC and placebo was performed in a double blind cross over design with 2 weeks wash-out between treatments. Eleven subjects with high plasma Lp(a) (> 0.3 milligram) were recruited from the Lipid Clinic at Sahlgren's Hospital, Göteborg, Sweden. Main outcome measures were treatment effects on plasma Lp(a) and plasma amino thiols (homocysteine, cysteine and cysteinyl glycine). There was no significant effect on plasma Lp(a) levels. Plasma thiols were significantly reduced during treatment with NAC: homocysteine by 45% (P < 0.0001), cysteinyl glycine by 24% (P < 0.0001) and cysteine by 11% (P = 0.0002). The high dose of NAC was well tolerated. In conclusion NAC has no effect on plasma Lp(a) levels while the reduction in homocysteine is considerable and might be of clinical significance in cases with high plasma homocysteine levels.

Acetylcysteine↗

Crystallization and preliminary x-ray diffraction study of 1 ,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea.

1,3,8-Trihydroxynaphthalene reductase was crystallized in the presence of NADPH and the inhibitor tricyclazole. The crystals are trigonal, space group P3(1)21 or its enantiomorph P3(2)21. Two crystal forms with slightly different cell dimensions were obtained. Form A has unit cell dimensions a = b = 142.6 angstrom, c = 70.1 angstrom and form B cell dimensions a = b = 142.6 angstrom, c = 72.9 angstrom. The diffraction pattern of the latter crystal form extends to 2.5 angstrom resolution.

Ascomycota↗

Measurements of movements during highly repetitive industrial work.

In the manufacturing industry highly repetitive movement patterns in the work situation are common. This work situation is often the cause of pain in the neck-arm region. To measure these movement patterns a new method has been developed by registering acceleration during ordinary industrial work. Three small accelerometers were fastened horizontally, transversely and vertically in a small box at the wrist. The data were fed into a computer memory at the work site and analysed later. The method can be used during ordinary work in a factory causing no interference to the work.

Journal Article↗

Pharmacokinetics of cisplatin and its monohydrated complex in humans.

The pharmacokinetics of cisplatin and its cytotoxic hydrolysis product cis-diammineaquachloroplatinum(II) ion (monohydrated complex) were investigated in seven patients after they received a 1-h infusion of cisplatin in normal saline at 100 mg/m2. The concentrations of intact cisplatin and the monohydrated complex were determined in blood by liquid chromatography with post-column derivatization, using diethyldithiocarbamate as the reagent. A pharmacokinetic model was developed assuming that a fraction of the dose (2.3%) is present as the monohydrated complex in the infusion solution and that reversible reactions between cisplatin and its monohydrated complex prevail. The clearances of cisplatin and the monohydrated complex were 0.32 +/- 0.05 and 0.27 +/- 0.11 L/min/m2, respectively. The apparent volume of distribution was considerably smaller for the monohydrated complex (4 +/- 2 L/m2) than for cisplatin (11 +/- 2 L/m2). The elimination rate constants were 0.030 +/- 0.002 and 0.07 +/- 0.02 min-1 for cisplatin and the monohydrated complex, respectively. The area under the time-concentration curve for the monohydrated complex was approximately 15% of that for cisplatin. It is concluded that the significant amounts of the monohydrated complex present in blood are due to the fraction already present in the administered dose and to the fraction formed in blood.

Antineoplastic Agents↗

Lazaroid treatment prevents death of cultured rat embryonic mesencephalic neurons following glutathione depletion.

Reactive oxygen species are believed to play a crucial role in situations where dopamine neurons die, such as in Parkinson's disease or during intracerebral transplantation of embryonic mesencephalic tissue. The present study was designed to address the question whether, and to what extent, the glutathione redox system is important for the viability of rat embryonic dopamine neurons in vitro. Furthermore, we studied whether the lazaroid U-83836E, a 2-methylaminochroman that inhibits lipid peroxidation, affects the survival of cultured mesencephalic neurons subjected to experimentally induced glutathione depletion. Glutathione depletion was achieved by exposing dissociated mesencephalic cell cultures to L-buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, at four different concentrations (1, 10,100, and 1,000 microM). Dopamine neuron survival was significantly reduced by 65-94% in a concentration-dependent manner by 10-1,000 microM BSO. The neurotoxic effects of BSO were almost completely prevented by supplementing the culture medium with 0.3 microM U-83836E. As assessed by HPLC analysis, BSO treatment was associated with a marked reduction of cellular glutathione content, and this depletion was not altered by the presence of U-83836E. We conclude that in the present insult model of severe glutathione depletion, the lazaroid can afford efficient neuroprotection that does not seem to be mediated by a direct interaction with BSO or glutathione, but rather via an independent pathway.

Analysis of Variance↗