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Biomedical subjects

M Svensson

Publications and source records attributed to M Svensson.

At least 127 records · Page 7Linked to original sources
PubMed1993

Synaptic density of axotomized hypoglossal motorneurons following pharmacological blockade of the microglial cell proliferation.

The purpose of the present study was to examine the possible role of reactive microglia in the removal of presynaptic terminals following motor axon injury. Quantitative electron microscopy was used to examine synaptic numbers and total relative synaptic coverage on hypoglossal neuronal perikarya following hypoglossal nerve transection in the rat with or without pharmacological blockade of the axotomy-induced microglial cell proliferation. In a previous study we have shown that the axotomy-induced microglial cell proliferation is selectively inhibited by continuous infusion of cytosine-arabinoside (ARA-C) into the ventricular system of the adult rat brain. Adopting this procedure in the present study resulted in an almost complete elimination of reactive microglia. There was a statistically significant decrease in the number of synapses and the relative synaptic coverage in untreated as well as ARA-C-treated animals 4 and 7 days after nerve transection. Immunocytochemical labeling of terminals in the hypoglossal nucleus using antibodies to synaptophysin showed a reduction in immunoreactivity around hypoglossal nerve cell bodies ipsilateral to nerve transection in both groups of animals. These results indicate that reactive microglia are not responsible for detachment of presynaptic terminals following motor axon injury.

Animals↗
PubMed1993

A quantitative analysis of the microglial cell reaction in central primary sensory projection territories following peripheral nerve injury in the adult rat.

The time course of the microglial cell reaction in central nervous system primary sensory projection territories has been examined following peripheral nerve injury in the adult rat using qualitative and quantitative analysis of immunoreactivity with the monoclonal antibody OX-42, which recognises the complement receptor CR3. The regions examined included the gracile nucleus, the column of Clarke and the spinal cord dorsal horn (superficial and deep laminae separately) after unilateral sciatic nerve transection, and the spinal trigeminal nucleus following unilateral infraorbital nerve transection. In all territories examined a qualitative increase in OX-42 immunoreactivity was observed 24 h postlesion. Further, quantitative analysis revealed an exponential development of the OX-42 immunoreactivity, with a peak at one week postlesion, thereafter showing a slow exponential decline. Our results show that the signal (or signals) that induces the microglial cell response in primary sensory projection territories is rapid in comparison to previously described central degenerative changes following peripheral nerve lesions (transganglionic degeneration). These findings are compatible with the hypothesis that activated microglia play a pathogenetic role in the development of transganglionic degeneration.

Afferent Pathways↗
PubMed1993

Diversity among reactive astrocytes: proximal reactive astrocytes in lacerated spinal cord preferentially react with monoclonal antibody J1-31.

An Astrocyte-specific antigen recognized by monoclonal antibody J1-31 is a more intense marker for proximal reactive astrocytes in lacerated rat spinal cord than is glial fibrillary acidic protein (GFAP). Thus, MAb J1-31 recognizes reactive astrocytes in the immediate vicinity of the lesion, whereas reactive astrocytes that are located at a distance from the lesion are not detected by immunofluorescent staining. These findings are relevant to the biochemical heterogeneity manifested respectively by reactive astrocytes located proximal and distal to a laceration-type injury of the spinal cord, and those that develop following axotomy with retrograde degeneration. Reactive astrocytes in the axotomy model are not stained with MAb J1-31, but are positive for GFAP.

Animals↗
PubMed1993

The response of central glia to peripheral nerve injury.

Microglial and astroglial cells undergo prompt responses to peripheral motor and sensory axon injury. These responses include proliferation of microglial cells as well as hypertrophy and increased levels of glial fibrillary acidic protein around the axotomized motoneurons and in the central projection territories of peripherally axotomized sensory ganglion cells. Proliferating microglial cells migrate towards reacting motoneurons, however, without directly apposing their cell membrane. Astroglial cells, on the other hand, increase their structural interrelationship with reacting motoneurons, seemingly at the expense of some presynaptic terminals. In sensory projection areas, microglial cells phagocytose degenerating axons and terminals. Beyond these observations, the functional role of the central glial cell response to peripheral nerve injury is obscure.

Animals↗
PubMed1993

Cyclosporin A does not inhibit IL-1 alpha-induced epithelial cell IL-6 secretion.

Trauma and infection activated a murine mucosal IL-6 response in different ways: the IL-6 response to bacteria was sensitive to Cyclosporin A (CsA); the IL-6 response to trauma was not. The aim of the present study was to identify possible activators of the CsA-insensitive IL-6 secretion at the epithelial cell level. Two human epithelial cell lines from the kidney (A498) and bladder (J82) were exposed to Escherichia coli Hu734, interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor alpha (TNF-alpha). The E. coli strain had been used for the in vivo experiments which led to this study, and IL-1 alpha and TNF-alpha were likely to be released during infections and trauma. The secretion of IL-6 into the supernatants was compared between cells stimulated in the presence or absence of CsA. E. coli Hu734, IL-1 alpha and TNF-alpha stimulated an IL-6 response in the two epithelial cell lines. The IL-1 alpha-induced IL-6 response was rapid, and the secreted IL-6 levels were significantly higher than those induced by E. coli Hu734 or TNF-alpha. The IL-6 response to IL-1 alpha was insensitive to CsA. By contrast, the IL-6 response to E. coli Hu734 and TNF-alpha was inhibited by CsA. These results demonstrated that the inhibitory effect of CsA depends on the stimulus triggering the IL-6 response. IL-1 alpha may play a role in the induction of trauma-associated CsA-insensitive IL-6 secretion.

Animals↗
PubMed1993

The influence of surgically induced acute liver failure on the intestine in the rat.

The influence of acute liver failure induced by 90% hepatectomy on the intestine was evaluated in the rat. Small-intestinal mucosal mass decreased 2 h after hepatectomy. Microvillous height decreased significantly from 1 h and on, and villous height and area in the distal small intestine from 2 h after operation. Ninety per cent hepatectomy resulted in a decrease in systemic arterial blood pressure and an increase in portal venous pressure. Subserosal microcirculation and small-arterial circulation in the proximal and distal small intestine and colon decreased significantly after 90% hepatectomy. Overgrowth and colonization of Escherichia coli occurred in the distal small intestine from 1 h and on after hepatectomy. Protein content in enterocytes and bile secretion from the liver remnant were markedly reduced in hepatectomized rats. Thus, the present study shows evidence of alterations in intestinal morphology and function that can contribute to explain the enteric bacterial translocation after surgically induced acute liver failure.

Animals↗
PubMed1993

Bacterial adherence and epithelial cell cytokine production.

Epithelial cell lines produce the cytokines IL-1 alpha, IL-6 and IL-8 when stimulated with Escherichia coli. The cytokine response is enhanced by P fimbriae. The epithelial cell lines also respond to stimulation with other cytokines. These in vitro findings were confirmed in vivo in patients with E. coli infection who secreted IL-6 and IL-8 into the urine. The observations suggest that epithelial cells play a more active role in the mucosal immune response than previously recognized.

Animals↗
PubMed1992

Isomerase and chaperone activity of prolyl isomerase in the folding of carbonic anhydrase.

Several proteins have been discovered that either catalyze slow protein-folding reactions or assist folding in the cell. Prolyl isomerase, which has been shown to accelerate rate-limiting cis-trans peptidyl-proline isomerization steps in the folding pathway, can also participate in the protein-folding process as a chaperone. This function is exerted on an early folding intermediate of carbonic anhydrase, which is thereby prevented from aggregating, whereas the isomerase activity is performed later in the folding process.

Amino Acid Isomerases↗
PubMed1992

The effect of axon injury on microtubule-associated protein MAP2 mRNA in the hypoglossal nucleus of the adult rat.

High molecular weight microtubule-associated protein 2 (HW MAP2) is heavily concentrated in mature dendrites and may be critical for dendritic stability. Motor axon injury results in retraction of the dendritic tree which is associated with a decrease in MAP 2-like immunoreactivity (-LIR). Here we have shown with in situ hybridization that motor axon injury results in reduced expression of HW MAP2 mRNA in affected neurons. We conclude that axotomy induces a down-regulation of HW MAP2 synthesis.

Animals↗
PubMed1992

Cis-trans isomerization is rate-determining in the reactivation of denatured human carbonic anhydrase II as evidenced by proline isomerase.

The refolding of human carbonic anhydrase II is a sequential process. The slowest step involved is the recovery of enzymic activity (t1/2 = 9 min). Kinetic data from 'double-jump' measurements indicate that proline isomerization might be rate determining in the reactivation of the denatured enzyme. Proof of this is provided by the effect of proline isomerase on the reactivation kinetics: the presence of isomerase during reactivation lowers the half-time of the reaction to 4 min, and inhibition of proline isomerase completely abolishes this kinetic effect. A similar acceleration of the refolding process by proline isomerase is also observed for bovine carbonic anhydrase II, in contrast to what has previously been reported. In human carbonic anhydrase II there are two cis-peptidyl-Pro bonds at Pro30 and Pro202. Two asparagine single mutants (P30N and P202N) and a glycine double mutant (P30G/P202G) were constructed to investigate the role of these prolines in the rate limitation of the reactivation process. Both in the presence and absence of PPIase the P202N mutant behaved exactly like the unmutated enzyme. Thus, cis-trans isomerization of the Pro202 cis-peptidyl bond is not rate determining in the reactivation process. The mutations at position 30 led to such extensive destabilization of the protein that the refolding reaction could not be studied.

Amino Acid Isomerases↗
PubMed1992

Long-term effects of glipizide on insulin secretion and blood glucose control in patients with non-insulin-dependent diabetes mellitus.

Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached less than or equal to 6.0 mmol.l-1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of -2.8 kg by dietary control, did achieve a fasting blood glucose less than or equal to 6.0 mmol.l-1 after addition of less than or equal to 20 mg glipizide daily. They had a sustained (greater than or equal to 2 years) increase in meal-induced insulin secretion (32% increase in postprandial C-peptide AUC), and a sustained reduction in postprandial hyperglycaemia (34% reduction in AUC). Ten of the patients took a mean daily dose less than 5 mg (4.8 mg) and had a sustained increase in insulin secretion rate (increased C-peptide slope). The 15 patients had no elevation of basal insulin secretion and no impairment of weight reduction. The remaining 8 subjects, who showed little or no weight reduction on dietary control, had little or no reduction in fasting blood glucose despite long-term treatment with 20 mg glipizide daily, a less sustained increase in meal-induced insulin secretion, a smaller reduction of postprandial hyperglycaemia, and an increase in body weight. On diagnosis the 8 subjects did not differ from the other 15 subjects in age, body weight, blood glucose, HbA1c, C-peptide or insulin, nor in their glucose and insulin responses to a test dose of glipizide; the main reason for the apparent drug failure appeared to be deficient compliance with dietary regulation rather than a primary inability to respond to sulphonylurea treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

The effect of axon injury on microtubule-associated proteins MAP2, 3 and 5 in the hypoglossal nucleus of the adult rat.

Microtubule-associated proteins appear to be critical elements in the stabilization of microtubules during neurite development. Axon injury results in a new burst of axonal growth activity as well as in partial dendritic involution. With this background we have examined the immunocytochemical staining pattern for microtubule-associated proteins 2, 3 and 5 in the hypoglossal nucleus of adult rats following unilateral hypoglossal nerve resection. From four days to six weeks postlesion a significant reduction in microtubule-associated protein 2-like immunoreactivity was observed in the neuropil and neuronal perikarya of the hypoglossal nucleus ipsilateral to nerve transaction. Microtubule-associated protein 5-like immunoreactivity was reduced in neuronal perikarya and neuropil four days to two weeks after injury. After six weeks microtubule-associated protein 5-like immunoreactivity had returned to normal levels. Microtubule-associated protein 3-like immunoreactivity, which was observed in glial cell perikarya and axons, but not neuronal perikarya or dendrites, appeared to be essentially unaltered. The reduced levels of microtubule-associated proteins 2 and 5 may be factors contributing to previously documented axotomy-induced dendritic retraction. The decrease in microtubule-associated protein 5 staining and absence of microtubule-associated protein 3 expression in axotomized neurons contrast with the situation in developing neurons, and demonstrate that the neuronal reaction to axon injury in mature mammals involves a specific series of events distinct from the developmental process.

Animals↗
PubMed1992

Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury.

Following hypoglossal nerve transection in adult rats, immunoreactivity for complement factor C3 and one of its degradation products C3d as well as C4d and immunoglobulin G (IgG) was observed in the ipsilateral hypoglossal nucleus. Double-labelling experiments indicated that these antigens were present in perineuronally located reactive microglial cells. In addition, increased levels of complement factor C3-mRNA was found in perineuronally located cells ipsilateral to nerve lesion. These results suggest that the complement cascade is locally activated in the vicinity of axotomized neuronal perikarya and that microglial cells have a key role in this process, alternatively that C3, C3d, C4d and IgG are involved in other so far unknown processes.

Animals↗
PubMed1992

Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro.

This study demonstrated that epithelial cell lines secrete interleukin-6 (IL-6) in response to stimulation with gram-negative bacteria. Human epithelial cell lines of urinary tract origin (A-498 and J82) and of intestinal origin (HT-29 and Caco-2) were analyzed for the secretion of IL-6 by using the B9 bioassay. The supernatants from cells maintained with culture medium were used to assess the constitutive production of IL-6. The supernatants from cells exposed to Escherichia coli strains, lipopolysaccharide, lipid A, and isolated fimbriae were used to quantitate the IL-6 response to these stimulants. The urinary tract epithelial cell lines were found to constitutively secrete IL-6. The IL-6 activity in the supernatants of the bladder cell line (J82) increased above constitutive levels after 2 h of stimulation by most of the bacterial strains tested. The IL-6 activity in the supernatants of the kidney line (A-498) accumulated at a constant rate over the 24-h assay period. The role of bacterial adherence for the induction of IL-6 production was investigated by comparing the responses to recombinant E. coli strains expressing different fimbriae. In addition, isolated P and S fimbriae with and without the receptor binding domain were also used as stimulants. The IL-6 activity in the supernatants of the bladder cell line increased after exposure to bacteria and bacterial products regardless of their adhesive properties. In contrast, the kidney cell line was stimulated to secrete significantly more IL-6 by adhering bacteria and by adhesin-positive P fimbriae than by nonadhering bacteria or adhesin-negative P fimbriae. The S-fimbrial preparations had no specific effects on the IL-6 activity of the cell supernatants. These results are consistent with our hypothesis that epithelial cells can be a major source of IL-6 when stimulated by bacteria and that the adhesive properties of the bacteria can influence this response.

Bacterial Adhesion↗
PubMed1992

Comparison of terbutaline Turbuhaler and albuterol chlorofluorocarbon (CFC) inhaler in middle-aged and elderly patients with obstructive lung disease.

The aim of the present study was to compare the effect of terbutaline Turbuhaler (0.5 mg qid) with that of albuterol chlorofluorocarbon (CFC) inhaler (0.2 mg qid) in middle-aged and elderly patients with obstructive lung disease. The study was performed as an open cross-over (2 x 2 weeks) and randomized study in 85 patients. A significant increase in PEF was seen after inhalation from both devices (P less than .001). Baseline PEF values before inhalation were higher with Turbuhaler than with the CFC inhaler both in the mornings and in the evenings. Fifty-six percent of the patients preferred terbutaline Turbuhaler and 26% albuterol CFC inhaler (P = .004).

Administration, Inhalation↗