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Biomedical subjects

A Andersson

Publications and source records attributed to A Andersson.

At least 253 records · Page 14Linked to original sources

Effects of long-term chloroquine exposure on the phospholipid metabolism in retina and pigment epithelium of the mouse.

The influence of 6 month's treatment of normal mice with chloroquine on neuroretina and retinal pigment epithelium has been investigated biochemically and morphologically. All classes of neuroretinal phospholipids, except lysophosphatidylcholine, showed increased 14C-glucose incorporation after chloroquine treatment. No metabolic changes were observed in the pigment epithelium after the chloroquine treatment. Morphological signs of phospholipidosis were only evident in the ganglion cells of the neuroretina. It is concluded that long-term treatment with chloroquine does not affect pigment epithelium phospholipid metabolism but leads to morphological and biochemical signs of phospholipidosis in the neuroretina.

Animals↗

Assignment of two rat dihydrofolate (DHFR) genes to chromosomes 2 and 4.

A panel of rat x mouse cell hybrids was used in the chromosomal mapping of the rat dihydrofolate reductase (DHFR) gene. It was determined that the probe hybridized to gene sequences on two different chromosomes (Nos. 2 and 4), possibly representing the active gene and a pseudogene. Hybridization of the DHFR probe to DNA from a methotrexate resistant rat cell line revealed that the gene on chromosome 2 was amplified, but not the gene on chromosome 4. This result was taken to suggest that the active DHFR gene is located on rat chromosome 2 and that the sequence on chromosome 4 is a pseudogene.

Animals↗

Hyperglycemia-induced B cell toxicity. The fate of pancreatic islets transplanted into diabetic mice is dependent on their genetic background.

The role of pancreatic B cell dysfunction in the phase preceding clinical onset of insulin-dependent and non-insulin-dependent diabetes mellitus has been much debated. In this investigation, the impact of a prolonged diabetic environment on pancreatic islet B cells transplanted syngeneically under the kidney capsule of C57BL/6 (B6) and C57BL/Ks (BKs) mice was studied. Alloxan-diabetic mice bearing a subcapsular islet graft insufficient to normalize the blood glucose level were rendered normoglycemic by a second intrasplenic islet graft after various period of hyperglycemia to examine the reversibility of hyperglycemia-induced B cell dysfunction. Using a perfusion technique of the graft-bearing, it was found that both strains of mice exhibited a diminished glucose-induced insulin secretion after 6 wk of hyperglycemia, when compared with normoglycemic mice carrying islet grafts. When normoglycemia was restituted by the splenic graft after 4 or 12 wk, there was a normalization of glucose-stimulated insulin secretion in the renal islet grafts in B6 mice, whereas insulin secretion from the grafted BKs islets remained impaired. Morphometric measurements of the islet grafts demonstrated a 50% reduction in the graft volume in diabetic BKs mice after 12 wk, compared with normoglycemic animals, whereas no such decrease was observed in B6 mice. Islet grafts removed from hyperglycemic mice of both strains exhibited diminished insulin mRNA contents, and in the BKs mice there was also a reduced glucose oxidation rate in the islet grafts in vitro. This metabolic dysfunction can only partly be explained by a reduced graft size. The present findings emphasize the genetic constitution as a decisive factor for the survival and function during a period of sustained stress on a limited B cell mass.

Animals↗

Contractile effect of oxytocin and 1-deamino-1-carba-2-tyrosine (0-methyl)-oxytocin in myometrial tissue from non-pregnant and term pregnant women.

The contractile effect of the analogue 1-deamino-1-carba-2-tyrosine (0-methyl)-oxytocin (carbetocin) on isolated strips from the human myometrium was compared with that of oxytocin. Neither oxytocin nor carbetocin affected contractile activity in strips from non-pregnant women, but both peptides stimulated contractile activity in strips from women at term pregnancy (2 x 10(-11) mol/l, and 10(-10) mol/l, respectively). Thus, carbetocin is almost as potent as oxytocin with regard to stimulating myometrial contractions at term.

Adult↗

Attachment and detachment of human epidermal melanocytes.

Human epidermal melanocytes can leave their basal position following topical application of sodium lauryl sulphate. They thereby undergo changes which strongly indicate that the dense plates along their cytomembrane constitute a mechanism for attachment to the basal lamina. These detached melanocytes move rapidly to, or are transported to, more superficial levels of the living epidermis. They are probably not desquamated, but disintegrate within the stratum spinosum. It was remarkable that one melanocyte was found that broke the basal lamina, showing that melanocytes are capable of migrating, under certain conditions. A special fixation method which exposes the cytomembranes and allows the demarcation of cells and their finest cytomembrane protrusions was used to demonstrate that keratinocytes often bulge into the innermost spinous layer and become attached to the basal lamina only via more or less thin cytoplasmic protrusions. This is in contrast to the routine textbook description of a basal layer that consists of a strict single row of cuboid or columnar keratinocytes.

Administration, Cutaneous↗

Purification of Shiga toxin by alpha-D-galactose-(1----4)-beta-D-galactose-(1----4)-beta-D-glucose-(1- ---) receptor ligand-based chromatography.

A simple and rapid method for Shiga toxin purification based on specific binding to the Gal alpha 1----4Gal beta 1----4Glc globotrioside trisaccharide covalently linked to polyacryl/polyvinyl (Fractogel) has been developed. A cell-free sonicate-filtrate of Shigella dysenteriae type 1, strain 114Sd was passed over the globotrioside-Fractogel column, and bound toxin eluted with 6 M guanidine-HCl. A yield of 36 mg pure toxin/1 sonicate-filtrate was obtained, i.e. a one step 1224-fold purification. The recovery of biologically active toxin was 87%. The toxin was purified to homogeneity as shown by native PAGE and SDS-PAGE.

Animals↗

Drug inhibition indicates a single-site model of the 5-HT uptake site/antidepressant binding site in rat and human brain.

Drug inhibition against [3H]paroxetine binding to rat cortex and human putamen was investigated in saturation experiments. The addition of 5-HT, imipramine, citalopram and clomipramine all produced changes in apparent binding affinity (Kd) without changes in the number of binding sites (Bmax). These data suggest that there is no heterogeneity of specific [3H]paroxetine binding, supporting a single site model of the 5-HT uptake site and antidepressant binding site.

Aged↗

DNA replication in transplanted and endogenous pancreatic islets of obese-hyperglycemic mice at different stages of the syndrome.

It was the aim of the present study to examine, at different stages of the obese-hyperglycemic syndrome, rates of islet-cell DNA replication in endogenous pancreatic and grafted islets of such mice. For this purpose obese-hyperglycemic mice were given an islet transplant prepared from lean mice under the kidney capsule. Two weeks later the animals were given an IP injection of 3H-thymidine one hour before being killed. Autoradiography of pancreas and kidney sections indicated the highest labeling index (LI) for the endogenous islet cells in the youngest obese mice (6 weeks old), which was more than fivefold higher than that of lean, normoglycemic controls. The LI, however, decreased extensively with age. The transplanted islets had LI, which were higher and constant during the most intense period of the syndrome, but again there was a decrease in the oldest mice. By isolating and transplanting islets of the oldest obese mice (greater than 12 months) into younger obese mice, it was possible to revive the high cell replicatory activity of the ob/ob islets. Starvation for three days was found to markedly decrease the rate of islet cell DNA replication. Adrenalectomy of obese-hyperglycemic mice resulted in a decrease of the serum glucose and insulin concentrations; concomitantly, there was a decrease of LI of both transplanted and endogenous islets. Thus, it seems as if the attenuation of the hyperglycemia is most probably responsible for the decline of the islet cell replication with increasing age in obese-hyperglycemic mice.

Adrenalectomy↗

Aspects of pancreatic islet transplantation in diabetes mellitus.

The justification for pancreatic or islet transplantation in diabetes mellitus is to halt progression of diabetic vascular complications. Although this goal has so far not been achieved, technical progress in transplanting the whole or segmental, vascularized pancreas has been remarkable. However, the operation is complicated and not without risk; immune rejection is furthermore a major problem, and the availability of suitable organs is limited. Transplantation of isolated pancreatic islet grafts, i.e. isolated islets or fetal pancreas, has therefore emerged as an attractive alternative. Iso-, allo- or xenografts of such preparations have been found to reverse diabetes in experimental animals. Only a minor operation is required and islets, although highly immunogenic, may be accessible to immunomodulation in vitro in order to decrease or abolish the allograft rejection and prevent cells from becoming targets for the autoimmune assault. However, problems and difficulties have emerged in this context also. Thus, islets are extremely difficult to isolate from the adult human pancreas. Such glands, be they adult or fetal, are not easily available, and clinical trials have so far remained without documented success. Considerable efforts are being made to overcome the difficulties encountered in islet transplantation. Attempts are being made to improve the techniques for preparation of clean and viable islets and to understand critical factors in the cellular interactions between the graft and the host after transplantation. Factors of importance in this context are the nutritional requirements of the graft and the vascularization process at the site of implantation. In order to provide unlimited access to cells with a high potential for insulin production and adaptive growth in the diabetic recipient, ongoing research is also directed towards methods for preparation of porcine fetal and adult islets suitable for xenotransplantation. The obvious problems involved in immune rejection of the grafted tissue are being investigated with respect both to the possibility of immunomodulation of the graft in vitro, the design of new immunosuppressive drugs, and the possibility of immuno-isolation of the insulin-producing cells with the aid of artificial membranes.

Diabetes Mellitus↗

Evaluation of extracorporeal shock wave lithotripsy without anesthesia using a Dornier HM3 lithotriptor without technical modifications.

In 210 patients with urolithiasis extracorporeal shock wave lithotripsy was performed without regional, general or infiltration anesthesia by means of a technically unmodified Dornier HM3 lithotriptor. The stone burden varied from small ureteral stones to complete staghorn stones. All patients were given premedication with pethidine and diazepam, and a lidocaine-prilocaine-containing cream was applied on the skin at the entry site of the shock wave. Energy usually varied between 14 and 16 kv. More than 90% of the patients reported the pain to be at most of moderate intensity and acceptable. Less than 3% found the treatment unpleasant. The results were compared to those obtained in 250 patients treated with anesthesia according to the original procedure, with a generator voltage of 18 to 23 kv. The number of extracorporeal shock wave lithotripsy sessions for ureteral and large stones was somewhat higher with the low energy method than with the original procedure. However, the therapeutic result in terms of renal units without stones after 4 weeks was similar to that recorded for patients treated with the anesthesia method. According to these promising results we believe that extracorporeal shock wave lithotripsy without anesthesia in an unmodified Dornier HM3 lithotriptor can be performed successfully in a majority of patients and is an attractive alternative to other technical modifications of the equipment.

Anesthesia↗

Extracorporeal shock wave lithotripsy of stones in the mid ureter.

We treated successfully 16 patients with stones in the mid ureter, that is overlying the pelvic bone, in the prone position with a Dornier HM3 lithotriptor. The lithotriptor was equipped with the original reflector and generator system, and all treatments were performed with only surface anesthesia of the skin and premedication with pethidine chloride and diazepam. Between 1 and 3 sessions were necessary with up to 2,000 shock waves at each session. The generator voltage was varied between 14 and 18 kv. After completion of extracorporeal shock wave lithotripsy all patients became free of stones without ureteroscopy or transureteral manipulation except for a ureteral catheter and fluid irrigation during treatment.

Diazepam↗

Determination of homocysteine in plasma by ion-exchange chromatography.

A rapid ion-exchange chromatographic method for determination of total homocysteine in plasma is presented. The method has a coefficient of variation of approximately 5%. A comparison with a slower method previously used in our laboratory showed a high correlation (r = 0.993). The risk of oxidation of homocysteine during the chromatography and the necessary level of dithiotreithol to prevent oxidation are also established.

Chromatography, Ion Exchange↗

Establishment and functional implications of B-cell connectivity.

We have discussed some aspects of the structure of the normal immune system, particularly the B-cell compartment. We have argued: that a basic property of the natural antibody repertoire is constituted by high degrees of connectivity within the immune system as well as between the system and other components of the organism; that the complementarities constituting this connectivity are based on self-self interactions, high degrees of degeneracy or somatically selected interactions and that these properties are conserved through evolution, to ensure self-reference; that by evolutionary selection, antibody V-genes encoding such structural properties are ensured to be expressed early in ontogeny. The set of highly connected cells will be kept through ontogeny and form the basis for a compartment of naturally-activated lymphocytes making up 10-15% of the total lymphocyte population. As suggested before, this pool of connected cells may be responsible for maintenance of normal network dynamics and prevention of autoaggression.

Amino Acid Sequence↗

Effects of (-)15-deoxyspergualin on pancreatic islet B-cell function in vitro and on the development of diabetes after multiple low dose streptozotocin administration.

The effects of (-)15-deoxyspergualin (15-DS), a newly described immunosuppressive drug, have been investigated on diabetes induced in mice treated with multiple low-dose streptozotocin (multiple SZ). Male C3D2F1 mice were treated with either intraperitoneal injections of saline or 15-DS (2.5 mg/kg body weight) for a total of 10 days, starting during the first day of SZ administration (5 days; 40 mg/kg body weight). On day 14, 15-DS-treated animals were still normoglycaemic, whilst on day 21 there was only a partial reduction in the hyperglycaemia compared to that found in the saline treated animals receiving SZ. 15-DS did not prevent hyperglycaemia in the long run (day 35-63). Furthermore, morphological examinations of pancreatic glands suggested that the insulitis in the pancreatic islets was delayed in the 15-DS-treated animals. In control experiments mice were treated with 15-DS+ the vehicle for SZ. This regimen did not hamper the glucose homeostasis of the animals. In vitro effects of 15-DS were also examined. Isolated islets from C3D2F1 mice were cultured at different concentrations of 15-DS (0.1-10.0 mg/l). After one week in culture, islet insulin release, islet insulin and DNA content were measured. The islets looked fluffy after culture at the higher 15-DS concentrations (4.0-10.0 mg/l) and at 10 mM almost all of the islets disappeared. A dose-dependent reduction of glucose-stimulated insulin release could also be seen. In other experiments islets were exposed to SZ and subsequently cultured in the presence of 0.5 mM 15-DS, however, 15-DS could not prevent the reduction in insulin release due to SZ exposure. Since 15-DS influences macrophage functions, the presently observed protective effects against the multiple SZ-treatment could reflect a reduced local interleukin-1 production in the islet vicinity. Alternatively, a lowered interleukin-1 secretion could prevent the activation of other immune cells involved in the destruction of B-cells.

Animals↗

Inhibition and dissociation of [3H]-paroxetine binding to human platelets.

Previous data on dissociation studies of [3H]-imipramine and [3H]-paroxetine binding to the human platelet 5-hydroxytryptamine (5-HT, serotonin) transporter have suggested that the binding is heterogeneous in nature and/or is subject to allosteric modifications through a separate low affinity site. The platelet 5-HT transporter is often used as a biological marker in psychiatric conditions. Therefore, it was of interest to further characterize the 5-HT uptake site by using [3H]-paroxetine. The 5-HT uptake inhibitors tested (citalopram, clomipramine, imipramine, norzimeldine and paroxetine) and 5-HT itself produced competitive inhibition patterns in saturation experiments, suggesting that these agents bind to the same site. In dissociation experiments in the presence of the 5-HT uptake inhibitors, the half-time values for dissociation were the same, whereas 5-HT slowed the dissociation. These data suggest that with the concentrations used of the 5-HT uptake inhibitors, they do not modify the 5-HT transporter. However, in the presence of 5-HT, the [3H]-paroxetine dissociation is decreased, suggesting an allosteric modification of the [3H]-paroxetine binding site.

Antidepressive Agents↗