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Biomedical subjects

L Björklund

Publications and source records attributed to L Björklund.

At least 19 recordsLinked to original sources
PubMed2004

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

OBJECTIVES: To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. DESIGN: Population-based cohort study. SETTING: Nationwide from all Departments of Medicine and Endocrinology in Sweden. SUBJECTS: A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. MAIN OUTCOME MEASURE: Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. RESULTS: Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. CONCLUSIONS: Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

Adolescent↗
PubMed2001

Evidence for target-specific nerve fiber outgrowth from subpopulations of grafted dopaminergic neurons: a retrograde tracing study using in oculo and intracranial grafting.

Efforts have been made to counteract the symptoms of Parkinson's disease by substituting the loss of dopaminergic neurons with fetal ventral mesencephalic grafts. One of the postulated limiting factors in this treatment is the relatively poor cell survival and limited graft-derived fiber outgrowth. Recent results documenting enhanced survival of grafted dopaminergic neurons showed no positive correlation to enhanced innervation of the striatal target. Therefore this study was undertaken to investigate whether all surviving grafted dopaminergic neurons projected to the striatal target. Hence, fetal ventral mesencephalic tissue was implanted adjacent to mature versus immature striatal tissue using in oculo and intraventricular grafting techniques. In in oculo grafting, fetal ventral mesencephalon was implanted simultaneously with fetal lateral ganglionic eminence (immature striatal target) or to already matured striatal in oculo grafts (mature striatal target). Furthermore, fetal ventral mesencephalon was implanted into the lateral ventricle adjacent to mature dopamine-depleted striatum. The retrograde tracer fluorogold was injected into the striatal portion of the in oculo cografts and into reinnervated areas of the adult brain. Immunohistochemistry revealed that a significantly larger proportion of tyrosine hydroxylase-positive neurons in the ventral mesencephalic graft was innervating in oculo immature striatal tissue, and hence was fluorogold-positive, in comparison with the number of tyrosine hydroxylase-positive neurons innervating mature striatal tissue. Moreover, intracranial transplantations showed that tyrosine hydroxylase-positive neurons were distributed within the grafts in dense clusters of cells. In most clusters tyrosine hydroxylase-positive cells were fluorogold-negative but calbindin-positive. In a few tyrosine hydroxylase-positive cell clusters, neurons were coexpressing fluorogold but were calbindin-negative. In conclusion, significantly more dopamine neurons projected to immature than to mature striatal tissue and thus, a subpopulation of grafted dopaminergic neurons was not projecting into adult striatum. Thus, the results from this study show that further attempts to enhance survival of grafted dopamine neurons in purpose to enhance graft-derived fiber outgrowth and efficacy should also consider different subtypes of dopamine neurons.

Animals↗
PubMed2000

Cloning of the sth gene from Azotobacter vinelandii and construction of chimeric soluble pyridine nucleotide transhydrogenases.

The gene encoding the soluble pyridine nucleotide transhydrogenase (STH) of Azotobacter vinelandii was cloned and sequenced. This is the third sth gene identified and further defines a new subfamily within the flavoprotein disulfide oxidoreductases. The three STHs identified all lack one of the redox active cysteines that are characteristic for this large family of enzymes, and instead they contain a conserved threonine residue at this position. The recombinant A. vinelandii enzyme was purified to homogeneity and shown to form filamentous structures different from those of Pseudomonas fluorescens and Escherichia coli STH. Chimeric STHs were constructed which showed that the C-terminal region is important for polymer formation. The A. vinelandii STH containing the C-terminal region of P. fluorescens or E. coli STH showed structures resembling those of the STH contributing the C-terminal portion of the protein.

Amino Acid Sequence↗
PubMed2000

Implantation of bioactive growth factor-secreting rods enhances fetal dopaminergic graft survival, outgrowth density, and functional recovery in a rat model of Parkinson's disease.

One of the drawbacks with fetal ventral mesencephalic (VM) grafts in Parkinson's disease is the limited outgrowth into the host striatum. In order to enhance graft outgrowth, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were administered by implantation of bioactive rods to the lateral part of the striatum to support grafted fetal VM implanted to the medial portion of the striatum. The polymer-based bioactive rods allow for a local secretion of neurotrophic factors over a time period of approximately 2 weeks. Moreover, glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta1 (TGFbeta1) were administered using the same technique. Concomitant administration of GDNF and TGFbeta1 was achieved by insertion of one GDNF and one TGFbeta1 rod. This was performed to investigate possible additive effects between GDNF and TGFbeta1. Rotational behavior, outgrowth from and nerve fiber density within the VM graft, and the number of TH-positive cells were studied. Functional compensation by reduction of rotational behavior was significantly enhanced in animals carrying bFGF and GDNF rods in comparison with animals carrying only VM graft. EGF and bFGF significantly increased the innervation density. Moreover, the nerve fiber density within the grafts was significantly enhanced by bFGF. Cell counts showed that a significantly higher number of TH-positive neurons was found in grafts treated with bFGF than that found in GDNF-treated grafts. An additive effect of TGFbeta1 and GDNF was not detectable. These results suggest that bioactive rods is a useful tool to deliver neurotrophic factors into the brain, and since bFGF was a potent factor concerning both functional, immunohistochemical and cell survival results, it might be of interest to use bFGF-secreting rods for enhancing the overall outcome of VM grafts into patients suffering from Parkinson's disease.

Animals↗
PubMed1998

Lazaroid-enhanced survival of grafted dopamine neurons does not increase target innervation.

The lazaroid U-74006F enhances survival of grafted ventral mesencephalic neurons. In this study the intraocular grafting model was used and survival and outgrowth from fetal ventral mesencephalic grafts treated with U-74006F was evaluated in nigrostriatal co-grafts. Fetal lateral ganglionic eminence was implanted into the anterior eye chamber and left to mature. Fetal ventral mesencephalon was then implanted and the eyes were treated with U-74006F. The lazaroid treatment enhanced survival of tyrosine hydroxylase (TH)-positive neurons, but did not enhance TH-positive nerve fiber growth into the striatal portions of the co-grafts. However, a marked increase in nerve fiber formation was found within the ventral mesencephalic grafts. In conclusion, increased cell survival enhanced nerve fiber formation within the ventral mesencephalic portion of the co-graft and not, as expected, in the striatal part.

Acetylcholinesterase↗
PubMed1998

Dopaminergic growth patterns induced by striatal and cortical grafts show differences in sensitivity to increased striatal trophic activity induced by haloperidol.

During development, dopaminergic neurons innervate the developing striatal target, forming two different growth patterns: a patchy growth and a diffuse growth. Chronic treatment with the dopamine antagonist haloperidol increase the neurotrophic activity in striatum, but it is not known how this trophic activity influences different patterns of dopaminergic growth. In this paper we have studied dopaminergic growth patterns by evaluating tyrosine hydroxylase (TH)-positive growth from mature midbrain dopaminergic neurons innervating grafted fetal lateral ganglionic eminence (LGE) or fetal cortical tissue implanted into the dorsal striatum. Host dopaminergic neurons innervated LGE grafts with a patchy growth pattern, leaving large portions of the striatal graft noninnervated, and cortical grafts with diffuse, nonpatchy growth, evenly distributed over the total volume of the graft. Both types of growth patterns were enhanced over time, albeit the most pronounced change was found in the nonpatchy pattern in the cortical grafts. When fetal LGE or cortical tissues were transplanted into the dorsal striatum of chronically haloperidol-treated animals, the nonpatchy growth into fetal cortical grafts was enhanced while the patchy growth into fetal striatal tissue was not. Taken together, the results suggest that both the patchy and diffuse growth patterns may be induced from adult midbrain dopaminergic neurons depending on the target of innervation, and that increased striatal trophic activity due to blockade of the dopaminergic input stimulates growth from a subpopulation of dopaminergic neurons that produce the nonpatchy growth.

Animals↗
PubMed1998

The Bone and Joint Decade 2000-2010. Inaugural meeting 17 and 18 April 1998, Lund, Sweden.

The increasing impact of bone and joint disorders on patients and healthcare systems, and an awareness that resources need to be more efficiently used, led to arrangements for a Consensus Meeting. This was held in Sweden in April 1998 and ended in an agreement to launch a Decade of Bone and Joint from 2000 to 2010. The aims of the Decade will be to raise awareness of the suffering and cost to society of musculoskeletal disorders such as joint diseases, osteoporosis, spinal disorders and severe trauma, and encourage research and development throughout the world.

Bone Diseases↗
PubMed1997

Tirilazad mesylate increases dopaminergic neuronal survival in the in Oculo grafting model.

Grafting of fetal ventral mesencephalon in Parkinson's disease has been extensively studied. A crucial draw back of this technique is the low survival rate of the dopaminergic neurons. It has been documented that only 5-20% of the grafted neurons survive, and to enhance graft efficacy to a satisfying level, increased cell survival is of utmost desire. In this study we have used the antioxidant tiriliazad mesylate (U-74006F) to study the effect on the survival of dopaminergic neurons after grafting. The in oculo grafting model was used and ventral mesencephalon was dissected from E14-E15 rat fetuses in Hanks' balanced salt solution (HBSS), in Dulbecco's modified Eagle medium (DMEM), or in 0.3, 3.0, or 30 microM U-74006F diluted in DMEM. The tissue was then inserted into the anterior chamber of the eye. Some of the transplants were further treated with intraocular injections of 3 or 30 microM U-74006F (5 microliters) weekly for 2 weeks. Quantification of tyrosine hydroxylase (TH)-immunoreactive profiles revealed that in transplants treated with U-74006F at dissection only, no change in the number of TH-positive neurons was found. Pretreatment of 0.3 microM U-74006F during dissection combined with intraocular injections of U-74006F after grafting, on the other hand, resulted in a dose-dependent enhancement of survival of TH-positive neurons. Dissection in, and intraocular treatment with, 3 microM U-74006F resulted in a significantly enhanced survival of TH-positive neurons whereas using U-74006F at a concentration of 30 microM did not change the cell survival compared to solely DMEM-treated grafts. Thus, 30 microM was interpreted to be an overdose. Comparing cell survival when dissected in DMEM with that dissected in HBSS showed that DMEM was clearly superior. Nerve fiber formation was most pronounced in grafts treated with 3 microM U-74006F. In conclusion, survival of TH-positive neurons is enhanced by U-74006F, which is readily available for clinical use and thus could be employed to enhance graft survival when transplanting patients suffering from Parkinson's disease.

Animals↗
PubMed1997

Dopaminergic innervation of striatal grafts placed into different sites of normal striatum: differences in the tyrosine hydroxylase immunoreactive growth pattern.

When patients with Parkinson's disease initially show symptoms, approximately 80-85% of their dopaminergic nerve fibers in the striatum have degenerated. It is thus of importance to develop strategies to try to rescue the remaining dopaminergic neurons and to stimulate them to induce sprouting. In this study the goal was to examine whether the different subgroups of dopaminergic neurons in the ventral mesencephalon projecting to the basal ganglia have different sprouting capacities when stimulated by the trophic effect of a fetal striatal graft. Lateral ganglionic eminence was implanted into the lateral ventricle, the midportion of dorsal striatum, globus pallidus, or ventral striatum. Solid tissue pieces from 13- to 15-mm fetuses were stereotactically implanted into adult female Sprague-Dawley rats. At postgrafting week 4 the animals were perfused and processed for tyrosine hydroxylase (TH) immunohistochemistry. Transplants placed in the lateral ventricle were TH-negative, except for two cases with TH-positive fibers where the ependymal layer was disrupted, thereby allowing direct contact between the graft and the adjacent host striatum. The transplants placed into dorsal striatum were innervated by small patches of dopaminergic nerve fibers. Areas between the TH-positive patchy structures remained TH-negative. In grafts placed into globus pallidus, both patchy structures and a less dense TH-positive nerve fiber network was noted. The TH-positive growth pattern in transplants placed in ventral striatum was also divided into patchy and widespread growth. Grafts placed in globus pallidus and ventral striatum revealed significantly larger areas of TH-positive innervation compared with that measured in grafts placed in dorsal striatum and the lateral ventricle. In conclusion, it is possible to induce sprouting of TH-immunoreactive nerve fibers from all areas examined. The most potent areas to initiate dopaminergic growth were the globus pallidus and ventral striatum, where both a patchy dense and a widespread, less dense growth was induced. Thus, if using a trophic stimulus to induce sprouting from remaining dopaminergic nerve fibers in Parkinson's disease, the preferential target to induce sprouting would be ventromedial striatum and growth would be guided toward dorsal striatum owing to the enhanced dopaminergic growth properties in the ventromedial areas.

Animals↗
PubMed1997

Changing trend in perinatal management and outcome of extremely low birthweight (ELBW) infants.

Perinatal care of the extremely preterm and low birthweight (ELBW) infant is founded on basic principles of physiology and knowledge about the prevailing pathophysiological mechanisms. New therapies in clinical care are usually introduced non-uniformly, so more often there is a gradual rather than a sudden change in the development of perinatal care, conceivably involving also an important learning process. This was confirmed in an evaluation of respiratory care for ELBW infants (n = 325) over a 9-year period (1986-1994). Although birthweight (mean 815 g) and degree of immaturity at birth (mean 26.7 weeks of gestation) did not change over the years, our trend analysis showed that the survival rate increased from 47% to 70% (p < 0.04) and the percentage of survivors without bronchopulmonary dysplasia and/or major intracranial haemorrhages (ICH grades 3 and 4) increased from 67% to 87% (p < 0.006). We suggest that besides medical treatment per se, refinement and tuning of nursing and medical care procedures will also affect the total outcome of ELBW infants.

Humans↗
PubMed1994

Dose-dependent effects of recombinant human NGF on grafted adult adrenal medullary tissue.

It has previously been shown that the chromaffin cells of the adrenal medulla respond to nerve growth factor (NGF) with neurite outgrowth and increased cell survival in tissue culture or after grafting. In the present study we evaluated the dose dependency in neurite outgrowth from chromaffin tissue to recombinant human NGF (rhNGF). Therefore, pieces of adrenal medullary tissue from adult rat were grafted into the anterior chamber of the eye of previously sympathectomized recepients. Survival time was 4 weeks. At grafting and at Days 7, 14, and 21 postgrafting, the eyes were injected with 5 microliters of rhNGF at concentrations of 10, 30, 60, 100, 150, and 200 micrograms/ml, or with a control solution. All grafts, including the controls, survived well and became vascularized. At the low doses of rhNGF, 10 and 30 micrograms/ml, a small area of the irides was reinnervated and the density of the nerve fiber network was low. The maximal response was obtained at 100 micrograms rhNGF/ml. Using larger concentrations of 150 and 200 micrograms rhNGF/ml, the density of the nerve fiber network did not change, but the reinnervated area of the irides was significantly decreased compared to the outgrowth seen in irides treated with 100 micrograms/ml. In conclusion, adult rat chromaffin tissue responds to rhNGF in a dose-dependent manner. However, at the highest doses used, the outgrowth area was suboptimal, although nerve fiber density was maximal. These results indicate that to obtain maximal effects, the dose of NGF is critical.

Adrenal Medulla↗
PubMed1993

Glial cell line-derived neurotrophic factor is expressed in the developing but not adult striatum and stimulates developing dopamine neurons in vivo.

The potential role of glial cell line-derived neurotrophic factor (GDNF) as a trophic molecule for midbrain dopamine neurons was examined using two different approaches: in situ hybridization and intraocular transplantation. The presence of mRNA for GDNF was noted in striatal and ventral limbic dopaminergic target areas in the developing (E20-P7) rat, but not the adult rat. Signals were also found in nondopaminergic areas during maturation, such as the cerebellar anlage, spinal cord, and thalamus. Lesions of the nigrostriatal pathway in neonatal or adult rats, using 6-hydroxydopamine injected into the medial forebrain bundle, did not elicit upregulation of mRNA for GDNF. Grafts of fetal ventral mesencephalon in the anterior eye chamber were exposed to repeated injections of GDNF, which elicited a marked and dose-dependent increase in transplant volume. A low (0.1 microgram/eye) and high (1 microgram/eye) dose of GDNF both led to a somewhat larger mean area of dopamine fiber outgrowth into host irides. In the transplants, cell counts of tyrosine hydroxylase (TH)-immunoreactive neurons revealed a doubling of cell numbers in the low-dose group and about four times as many cells in the high-GDNF-dose group compared to controls. Moreover, the density of TH-immunoreactive nerve fibers was markedly and significantly higher in transplants treated with the high GDNF dose. Since the volumes of these transplants were also larger, the total amount of both TH-positive cells and TH-positive nerve fibers was many-fold greater in the high-GDNF group than that in the controls. Taken together, these data support the concept that GDNF functions as a dopaminotrophic factor in vivo.

Aging↗
PubMed1992

Lung mechanics (FRC and static pressure-volume diagram) after endotracheal surfactant instillation: preliminary observations.

Preliminary measurements of functional residual capacity (FRC) with the sulphurhexafluoride technique and static pressure volume diagrams were performed in newborn infants with respiratory distress syndrome receiving endotracheal instillation of natural porcine surfactant (Curosurf, 100 or 200 mg/kg). Within the first hour after surfactant treatment there was an increase in FRC and distensibility of the lungs persisting for 24-48 h.

Biological Products↗
PubMed1990

Spontaneous pneumopericardium in an otherwise healthy full-term newborn.

Neonatal pneumopericardium is usually a complication of mechanical ventilation in premature infants with respiratory distress syndrome. We report a full-term neonate who developed pneumopericardium after forceps delivery and mild asphyxia. The child was never ventilated and had no signs of parenchymal lung disease. The pneumopericardium resolved spontaneously. Although drainage of pneumopericardium is usually recommended, this may not always be necessary when there are no signs of cardiac tamponade.

Humans↗