Biomedical subjects

A Andersson

Publications and source records attributed to A Andersson.

At least 145 records · Page 8Linked to original sources

PubMed1996

Structure and function of macroencapsulated human and rodent pancreatic islets transplanted into nude mice.

Macroencapsulation of human pancreatic islets inside biomembranes is a promising approach to maintain islet allografts in the diabetic recipient without immunosuppression. In order to test this possibility islets isolated from human pancreata were kept in culture before macroencapsulation in a tissue chamber device. The device consisted of two titanium rings, which supported two flat membranes. These membranes have previously been shown to protect pancreatic islets and fetal lung tissue from allograft rejection and also to promote neovascularization at the membrane surface. In a first series of experiments macroencapsulated human islets were implanted into the epididymal fat pad of athymic, nude mice concomitant to an injection from the same batch of islets under the kidney capsule. Light microscopy of encapsulated and subcapsularly grafted human islets showed that the survival inside the membranes was as good as under the kidney capsule. There was an extensive formation of new blood vessels at the membrane outer surface. In a second series of experiments insulin was extracted from encapsulated human islets implanted either into the epididymal fat pad or subcutaneously. The encapsulated human islets contained as much insulin as the non-encapsulated ones. In these experiments mouse and rat islets were also used. Rodent islets, however, survived less well than the human islets as evidenced by the markedly reduced insulin content values. In a third series of experiments human islets were loaded into the chambers and transplanted into nude mice without the concomitant implantation of non-encapsulated islets under the kidney capsule of the recipienets. Measurements of human C-peptide in serum samples obtained 4 to 8 weeks post-implantation showed considerable concentrations (0.70-185 ng/ml) in all animals. We conclude that isolated human islets survive when implanted into nude mice and continue to release insulin for several weeks. There are, however, species differences suggesting that rodent islets are much more susceptible to the environmental stress inside the membranes than human islets.

Adult↗

PubMed1996

Energy turnover in a sailing crew during offshore racing around the world.

Energy turnover during offshore sailing was studied in 11 male crew members of one team during the first three legs of the 1993-1994 Whitbread Round The World Race. The effect of racing on the energy balance of the crew members was studied by anthropometric measurements and dietary intake as calculated from food inventories before and after each leg. Energy turnover, calculated from dietary intake and release of endogenous energy as a result of changes in body composition, was higher than expected (about 18-20 MJ.d-1). These findings were confirmed using the doubly labeled water technique in six crew members during the third leg, in which mean energy turnover was found to be 19.3 MJ.d-1. Changes in body weight and composition indicated a negative energy balance during all legs.

Adult↗

PubMed1996

Hyperhomocysteinaemia--a common finding in a psychogeriatric population.

Plasma homocysteine concentration is a sensitive marker for cobalamin and folate deficiency. The previously reported high incidence of increased plasma homocysteine in psychogeriatric patients and the association between reduced concentrations of cobalamin, folate and neuropsychiatric symptoms led to the present study on 741 consecutive psychogeriatric patients. The concentrations of plasma homocysteine correlated significantly with blood folate, serum cobalamin and serum creatinine both in demented (n = 295) and in non-demented patients with other psychiatric disorders (n = 215). Plasma homocysteine concentrations were significantly increased in both the demented and the non-demented patients, whereas only the demented patients had lower blood folate and serum creatinine concentrations than 163 control subjects. Almost all of the different diagnostic groups of demented and non-demented patients exhibited significantly increased plasma homocysteine concentrations compared with control subjects. Significantly decreased blood folate concentrations were mainly found in the different diagnosis groups of demented patients. Plasma homocysteine concentrations in both demented and non-demented patients with serum cobalamin and blood folate above the lower 20th percentile of these vitamins in the control subjects were also studied. Despite these vitamin concentrations, both groups of patients still exhibited significantly higher plasma homocysteine concentrations than the control subjects, which may indicate an increased frequency of impaired genetic capacity to metabolize homocysteine in these patients. Patients with either dementia of vascular cause or a history of other occlusive arterial disease had a significantly higher plasma homocysteine concentration than those without a history of vascular disease.

Aged↗

PubMed1996

Sodium lauryl sulfate effect on the density of epidermal Langerhans cells. Evaluation of different test models.

The effect of different test models for sodium lauryl sulfate (SLS)-induced irritant contact dermatitis on epidermal Langerhans cells (LC) numbers was examined. Finn Chambers, 8 and 12 mm, containing 15 and 34 or 50 microliters, respectively, of 1% aq. solution of SLS were applied to human forearm skin for 48 h as single or repeated application. The results showed a clear difference between the effects with the 2 chamber sizes. The effect of the 8-mm chambers could result in increased, unchanged or decreased LC numbers, while 12-mm chambers always produced a decrease. These results seem to explain, at least partly, the discrepant results reported from various laboratories.

Adult↗

PubMed1996

The phylogeny of intestinal porcine spirochetes (Serpulina species) based on sequence analysis of the 16S rRNA gene.

Four type or reference strains and twenty-two field strains of intestinal spirochetes isolated from Swedish pig herds were subjected to phylogenetic analysis based on 16S rRNA sequences. Almost complete (>95%) 16S rRNA sequences were obtained by solid-phase DNA sequencing of in vitro-amplified rRNA genes. The genotypic patterns were compared with a previously proposed biochemical classification scheme, comprising beta-hemolysis, indole production, hippurate hydrolysis, and alpha-galactosidase, alpha-glucosidase, and beta-glucosidase activities. Comparison of the small-subunit rRNA sequences showed that the strains of the genus Serpulina were closely related. Phylogenetic trees were constructed, and three clusters were observed. This was also confirmed by signature nucleotide analysis of the serpulinas. The indole-producing strains, including the strains of S. hyodysenteriae and some weakly beta-hemolytic Serpulina strains, formed one cluster. A second cluster comprised weakly beta-hemolytic strains that showed beta-galactosidase activity but lacked indole production and hippurate-hydrolyzing capacity. The second cluster contained two subclusters with similar phenotypic profiles. A third cluster involved strains that possessed a hippurate-hydrolyzing capacity which was distinct from that of the former two clusters, because of 17 unique nucleotide positions of the 16S rRNA gene. Interestingly, the strains of this third cluster were found likely to have a 16S rRNA structure in the V2 region of the molecule different from that of the serpulinas belonging to the other clusters. As a consequence of these findings, we propose that the intestinal spirochetes of this phenotype (i.e., P43/6/78-like strains) should be regarded as a separate Serpulina species. Furthermore, this cluster was found to be by far the most homogeneous one. In conclusion, the biochemical classification of porcine intestinal spirochetes was comparable to that by phylogenetic analysis based on 16S rRNA sequences..

Animals↗

PubMed1996

Pancreatic islet blood flow in normal and obese-hyperglycemic (ob/ob) mice.

The present study evaluated whether a microsphere technique could be used for islet blood flow measurements in anesthetized mice. When this was confirmed, we applied the technique in different strains of mice. Approximately 9 x 10(4) microspheres could be given without interfering with mean arterial blood pressure. Mixing of the microspheres with arterial blood was adequate, and the extraction of microspheres in capillary beds was nearly 100%. In NMRI mice whole pancreatic blood flow was estimated to be 0.54 +/- 0.11 ml.min-1.g pancreatic tissue-1 and islet blood flow to be 18 +/- 4 microliters.min-1.g pancreas-1 (n = 12 animals per experiment), whereas corresponding values in lean C57Bl/6 mice were twice as high. In C57Bl/6 mice glucose (3 g/kg iv) doubled islet blood flow without affecting whole pancreatic blood flow, whereas no effect was seen after an equimolar dose of 3-O-methylglucose. In obese-hyperglycemic C57Bl/6 mice, islet blood flow was more than five times higher than in the lean C57Bl/6 mice when expressed as blood flow per gram pancreas. However, when islet blood perfusion was corrected for islet weight, it was lower in the obese than in the lean mice, suggesting an impaired ability in obese mice to increase blood flow in concert with the increased islet mass. This may contribute to the insufficient insulin secretion and resulting hyperglycemia seen in these animals.

Animals↗

PubMed1996

Human pancreatic beta-cell deoxyribonucleic acid-synthesis in islet grafts decreases with increasing organ donor age but increases in response to glucose stimulation in vitro.

Human pancreatic beta-cell proliferation may be crucial for the success of islet transplantation. The aim of this study was to test the hypothesis that adult human beta-cells proliferate in vitro and in vivo and respond with increased rates of replication to factors known to promote rodent islet-cell proliferation, i.e. glucose, human recombinant GH, and FCS. For this purpose, human islets were prepared from a total of 19 adult heart-beating organ donors and cultured for 48 h with or without the additives described above. 3H-thymidine was added to the medium during the last 60 min of culture. After immunohistochemical staining for insulin and autoradiography, the labeling index (LI; i.e. % of labeled beta-cells over total number of beta-cells) was estimated by light microscopy. Islets also were transplanted under the kidney capsule of normal or alloxan-diabetic nude mice. After 2 weeks, 3H-thymidine was injected and the islet grafts prepared for determination of LI, as described above. Islets cultured at 5.6 mM glucose showed an increased beta-cell proliferation compared with islets cultured at 2.8 mM glucose (P < 0.05). However, culture at 11 mM glucose failed to further increase beta-cell proliferation. Addition of GH (1 microg/ml) to the medium, in the presence of 1% FCS and 5.6 mM glucose, did not influence the rate of beta-cell proliferation. In islets transplanted to hyperglycemic nude mice, beta-cell proliferation was similar to that observed in islets grafted into normoglycemic nude mice. Proliferation, however, decreased with increasing organ donor age. This study shows that pancreatic beta-cells from adult man are able to proliferate both in vitro and in vivo. Moreover, beta-cells from adult human donors respond with increased proliferation to glucose in vitro and show a decreased proliferation in vivo with increasing donor age.

Adolescent↗

PubMed1996

In vivo effects of 13-cis retinoic acid treatment on the concentration of proteins and lipids in serum.

A number of serum components, whose concentrations or gene expression have been shown to be modulated by all-trans retinoic acid in vitro, were monitored in patients before and during treatment with Roaccutane (13-cis retinoic acid, 40-60 mg/day) for severe acne. The 13-cis retinoic acid concentration in serum rose from 5.25 +/- 1.09 to 593 +/- 65 nmol/l (mean +/- SD) 24 h after the latest dose. The concentration of all-trans retinoic acid in serum under Roaccutane treatment was measured in model experiments and shown to be 10-20 nmol/l i.e., 2-4 times the basal levels (4.65 +/- 0.85 nmol/l) when the 13-cis retinoic acid concentration was 370-980 nmol/l. The concentrations of creatine kinase-MB, apolipoprotein B, total cholesterol and LDL cholesterol increased significantly while the other measured serum components, including lipoprotein lipase activity, were unaffected by Roaccutane treatment.

Acne Vulgaris↗

PubMed1996

Efficient gene transfer to dispersed human pancreatic islet cells in vitro using adenovirus-polylysine/DNA complexes or polycationic liposomes.

The establishment of gene delivery systems that result in efficient transfection of the pancreatic beta-cells may generate an important tool for the study of IDDM and may also represent one critical step toward a clinical application of gene transfer for the prevention or early treatment of the disease. Using the reporter gene vectors pCAT and pCMV beta-gal, we have investigated the efficiency of transfection mediated by calcium phosphate precipitation, the monocationic liposome Lipofectin, the polycationic liposome Lipofectamine, and adenovirus-polylysine (AdpL) DNA complexes in human, mouse, rat, and fetal porcine islet cells. In all species studied, calcium phosphate-mediated transfection resulted in lower chloramphenicol acetyl transferase (CAT) activities than the other methods. Intact human, mouse, and rat islets were poorly transfected by Lipofectin, Lipofectamine, and AdpL. When dispersed by trypsin treatment, however, human, mouse, rat, and fetal pig islect cells were efficiently transfected by Lipofectamine. Moreover, transfection of dispersed human and mouse islet cells using AdpL, also resulted in high CAT activities. The percentage of cells staining positively for beta-galactosidase after transfection with Lipofectamine was 49% for mouse, 56% for rat, and 57% for dispersed human islet cells. Transfection of human islet cells using AdpL, however, yielded 70% beta-gal-positive cells. Fluorescence-activated cell sorting-purified rat islet alpha- and beta-cells were transfected with similar efficiency using Lipofectamine. CAT expression in human islet cells transfected with either Lipofectamine or AdpL reached a peak value after 5-7 days, followed by a gradual decline. It is concluded that transfection with AdpL or Lipofectamine are both efficient means to achieve transient expression of gene constructs in human and mouse islet cells, while for rat and fetal porcine islet cells, Lipofectamine is the most efficient of the agents investigated in this study.

Analysis of Variance↗

PubMed1995

Metabolism of homocysteine, its relation to the other cellular thiols and its mechanism of cell damage in a cell culture line (human histiocytic cell line U-937).

This study shows that the intracellular concentration of homocysteine in cultured cells is kept low due to an accumulation in the medium. The intracellular level of homocysteine was decreased when its precursor, methionine, was omitted from the culture medium. Intracellular glutathione and cysteine were lowered in cystine-deficient medium. Intracellular glutathione was also lowered when copper ions were added to the culture medium. It is evident from this study that the intracellular concentration of homocysteine was not influenced by the lowered level of glutathione and/or cysteine. High amounts of homocysteine added to the medium give rise to an increase of intracellular reduced homocysteine, which participates in the transsulfuration pathway and can replace cysteine in the synthesis of glutathione. The addition of relatively high amounts of reduced homocysteine (500 mumol/l) in the presence of copper ions (100 mumol/l) to the culture medium can be directly toxic to the cells, possibly due to oxygen radicals formed by thiol auto-oxidation. Whilst the level of homocysteine in this study using short-time cell culture experiment is much higher than the mild hyperhomocysteinemia thought to be atherogenic in humans, it is conceivable that over a longer time course these levels of homocysteine could be sufficient to induce endothelial dysfunction, eventually leading to atherosclerosis.

Arteriosclerosis↗

PubMed1995

Purification and preliminary X-ray crystallographic studies of recombinant L-ribulose-5-phosphate 4-epimerase from Escherichia coli.

The araD gene from Escherichia coli, coding for L-ribulose-5-phosphate 4-epimerase, was overexpressed and the resulting enzyme was purified to homogeneity. Crystals of L-ribulose-5-phosphate 4-epimerase, obtained with 4.0 M sodium formate as precipitant, belong to space group P4212 with unit cell dimensions a = b = 107.8 A and c = 281.4 A and diffract to at least 2.2 A resolution. Density measurements of these crystals are consistent with eight subunits in the asymmetric unit.

Base Sequence↗

PubMed1995

Rapid deposition of amyloid in human islets transplanted into nude mice.

Human islets of Langerhans were transplanted to the subcapsular space of the kidneys of nude mice which were either normoglycaemic or made diabetic with alloxan. After 2 weeks, the transplants were processed for light and electron microscopical analyses. In all transplants, islet amyloid polypeptide (IAPP)-positive cells were found with highest frequency in normoglycaemic animals. IAPP-positive amyloid was seen in 16 out of 22 transplants (73%), either by polarisation microscopy after Congo red staining or by immune electron microscopy. At variance with previous findings of amyloid deposits exclusively in the extracellular space of islets of non-insulin-dependent diabetic patients, the grafted islets contained intracellular amyloid deposits as well. There was no clear difference in occurrence of amyloid between diabetic and non-diabetic animals. The present study indicates that human islets transplanted into nude mice very soon present IAPP-positive amyloid deposits. This technique may provide a valuable model for studies of the pathogenesis of islet amyloid and its impact on islet cell function.

Adolescent↗

PubMed1995

Distribution of cisplatin in perilymph and cerebrospinal fluid after intravenous administration in the guinea pig.

The concentration of free cisplatin was followed in plasma, scala tympani perilymph and cerebrospinal fluid (CSF) after an intravenous injection (12.5 mg/kg) in guinea pigs. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the drug. The distribution of cisplatin to CSF was fast; at 10 min after drug administration the concentration was 7 micrograms/ml and the CSF:plasma ratio was 0.37. Cisplatin seems to distribute more slowly to the perilymphatic compartment. The highest concentration measured was 4 micrograms/ml at 20 min after the injection, and the perilymph:plasma ratio was 0.40 at that time. The concentration-time curves generated for cisplatin in perilymph and CSF were similar. No accumulation in the perilymphatic compartment or CSF was observed.

Animals↗

PubMed1995

Low serum concentration of all-trans and 13-cis retinoic acids in patients treated with phenytoin, carbamazepine and valproate. Possible relation to teratogenicity.

All-trans retinoic acid deficiency resulting from ethanol's interference with the synthesis of all-trans retinoic acid from retinol was recently suggested to cause the malformations of the fetal alcohol syndrome. Phenytoin, carbamazepine and valproate, might be teratogenic because they lower the concentration of all-trans retinoic acid in serum, by inducing the enzyme systems in the liver responsible for the metabolism of the all-trans retinoic acid, or by other mechanisms. Here we show, that in patients given therapeutic doses of phenytoin, carbamazepine and valproate, serum all-trans and 13-cis retinoic acid concentrations are indeed significantly lowered. We propose that drugs with this ability should be considered as potential teratogens.

Adult↗

PubMed1995

What problems does the food industry have with the spore-forming pathogens Bacillus cereus and Clostridium perfringens?

Spore-forming bacteria are special problems for the food industry. It is not always possible to apply enough heat during food processing to kill spores, thus we have to take advantage of knowledge of the spore-formers to control them. For the meat industry Clostridium perfringens might become a special problem, although this bacterium mainly causes food poisoning through food served in restaurants, hospitals or homes for elderly people (Cliver, 1987; Reynolds, 1987; Gondrosen et al., 1990). The reason for the food poisoning is always the same: meat-containing dishes stored after cooking with insufficient cooling and reheating (Granum, 1990). Even though it should be relatively easy to control this kind of food poisoning, C. perfringens is still one of the most common sources of foodborne diseases. Proper disinfection is necessary to control this type of food poisoning, as it is now clear that only kitchen strains of C. perfringens are able to produce the large amounts of enterotoxin necessary to cause food poisoning (Granum, 1990; Cornillot et al., 1995). Bacillus cereus is more difficult to control, specifically in the dairy industry, where it is now causing the main problems. Insufficient heating of rice-containing dishes has been known to cause B. cereus food poisoning of the emetic kind for a long time (Kramer and Gilbert, 1989), but will not be dealt with in this paper. There are several reasons for the problems in the dairy industry. First of all it seems to be impossible to completely avoid the presence of B. cereus in all milk samples. Secondly the spores are very hydrophobic (Husmark, 1993), and will attach to the surfaces of the pipelines of the dairy industry, where they might multiply and resporulate. A third problem is that pasteurisation heating is insufficient to kill the spores, while competition from other vegetative bacteria is eliminated. It seems that several B. cereus strains have become psychrotrophic over the years, making possible growth at temperatures as low as 4-6 degrees C (Granum et al., 1993a). None of the methods used to control hygiene in the dairy industry so far are able to control B. cereus. This is a continuously increasing problem for the industry but, with emerging knowledge, we should be able to control it. In this paper we will discuss the problems the food industry is facing with C. perfringens and B. cereus, and how these problems might be solved. We will also give our view on how research might ease these problems in the future.

Animals↗

PubMed1995

The membrane glycoprotein G1 of Uukuniemi virus contains a signal for localization to the Golgi complex.

Members of the Bunyaviridae family acquire their envelopes by budding into the Golgi complex (GC). The accumulation of the membrane glycoproteins G1 and G2 in the GC probably determines the site of maturation. Here we have studied the intracellular transport and targeting to the GC of G1 and G2 of Uukuniemi virus, a member of the Phlebovirus genus, and report on their expression from cloned cDNAs either together or separately by using a T7 RNA polymerase-driven vaccinia virus expression system. When G1 and G2 were expressed together from a full-length cDNA as the p110 precursor, both proteins were localized to the Golgi complex, as evidenced by colocalization with the Golgi marker enzyme mannosidase II. Immunofluorescent staining indicated that G1 expressed alone also localized to the GC. However, pulse-chase experiments showed that G1 remained endoglycosidase H sensitive. G2 expressed alone remained associated with the endoplasmic reticulum (ER). G2 could be rescued from the ER and transported to the GC by coexpression with G1 from separate mRNAs. Coexpression also increased the efficiency of G1 transport to the GC. With none of the constructs could the glycoproteins be observed on the cell surface. These results show that efficient export of G1 and G2 from the ER requires coexpression of both proteins, in conformity with our previous results showing that G1 and G2 form heterodimeric complexes in the ER. Since G1 expressed alone is retained in the GC, we conclude that G1 contains a retention signal for localization to the GC. G2 might thus become associated with the GC indirectly via its interaction with G1.

Biological Transport↗

PubMed1995

Stability of cisplatin and its monohydrated complex in blood, plasma and ultrafiltrate--implications for quantitative analysis.

The stability of cisplatin and its monohydrated complex has been studied in blood, plasma and plasma ultrafiltrate at 37 degrees C (pH 7.4). Intact cisplatin and the monohydrated complex were determined by liquid chromatography with post-column derivatization. The half lives for cisplatin and the monohydrated complex were 1.43 +/- 0.03 h (SEM) and 0.36 +/- 0.03 h (SEM), respectively, in blood and 0.88 +/- 0.05 h (SEM) and 0.26 +/- 0.02 h (SEM), respectively, in plasma. The compounds were unstable at -25 degrees C (t1/2 for cisplatin was 52 +/- 5 h (SEM) and for the monohydrated compound 26 +/- 2 h (SEM)), but at -70 degrees C both compounds were stable for at least 3 weeks. The monohydrated complex was found to be formed to a small extent when cisplatin was added to plasma (37 degrees C, pH 7.4). A sampling procedure using centripetal ultrafiltration of whole blood was evaluated and found applicable if the samples were stored at 0 degree C and ultracentrifuged within 1 h.

Cisplatin↗

PubMed1995

Estradiol and testosterone in specific regions of the human female brain in different endocrine states.

Post-mortem concentrations of estradiol and testosterone were measured in 17 brain areas, serum and fat in 6 fertile and 5 postmenopausal women. Steroid concentrations were measured with radioimmunoassay after extraction of brain tissue with ethanol and purification with celite chromatography. There were regional differences in brain concentrations of both steroids. The highest levels of estradiol and testosterone were noted in the hypothalamus, preoptic area and substantia nigra. These findings may assist in the interpretation of functional animal studies where the hypothalamus-preoptic area and the nigrostriatal dopamine system have proved to be target areas for estradiol. When compared to postmenopausal women, estradiol concentrations were significantly higher in the brains of fertile women, which indicates that peripheral serum levels of estradiol are reflected in the brain. This study has yielded information about steroid levels in different endocrine states and could provide a frame of reference for studies of estradiol and testosterone mediated effects on the central nervous system.

Adipose Tissue↗